Name: 36635-61-7|1-((Isocyanomethyl)sulfonyl)-4-methylbenzene|98%
Brand: Ambeed
SKU: A261697
Rating: 91 (28 reviews)

1
[ 1121-60-4 ]
[ 36635-61-7 ]
[ 70380-73-3 ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium carbonate In methanol at 65℃; for 4h; Inert atmosphere; Reflux;	copying of Exp details for full text of reaction could not possible.
98%	With potassium carbonate In methanol at 65℃; for 4h; Inert atmosphere;
98%	With potassium carbonate In methanol at 65℃; for 4h; Inert atmosphere;	4.2.1. General Method for Conversion of Aldehyde to Oxazole (Condition Set a) General procedure: In a round-bottom flask containing dry MeOH (10 mL/mmol of aldehyde) were added thealdehyde (1 equiv.), TOSMIC reagent (1.1 equiv.) and K2CO3 (2.2 equiv.), in this order. The flask wasfitted with a vertical condenser and the mixture was refluxed at 65 °C for 4 h. The solvent was entirely removed under reduced pressure and the residue was resuspended in EtOAc and stirred for 30 min atroom temperature. Filtration led to removal of insoluble materials and the solution was concentratedunder reduced pressure and applied to a silica column for flash chromatography. Elution took placeby using either a hexane/EtOAc step gradient (from 2:1 to 1:2 to pure EtOAc) or a CH2Cl2/MeOHstep gradient (from 99:1 to 90:10), depending on product polarity. This method was applied to thesynthesis of compounds 2, 9 and 13.5-(Pyridin-2-yl)oxazole (2): Reaction scale 20 mmol of aldehyde 1; Chromatography with hexane/EtOAcstep gradient; Product yellow oil; Yield 98%; 1H-NMR (CDCl3): δ (ppm) = 7.19 (1H, ddd, J1 = 7.8 Hz,J2 = 4.7 Hz, J3 = 1.0 Hz), 7.61 (1H, d, J = 7.8 Hz), 7.65 (1H, s), 7.71 (1H, dt, J1 = 7.8 Hz, J2 = 1.8 Hz), 7.93(1H, s), 8.58 (1H, d, J = 5.5 Hz); 13C-NMR (CDCl3): δ (ppm) = 119.0, 122.7, 124.5, 136.6, 146.7, 149.5,150.7, 150.8; MS (MALDI-TOF): m/z = 147.23 [M + H]+ (calcd. for C8H6N2O: 146.05).

97%	With potassium carbonate In methanol for 2h; Heating / reflux;	(Saikachi, H.; Kitagawa, T.; et al. Chem. Pharm. Bull. 1969, 27, 793-796). A solution of 2-pyridinecarboxaldehyde (2.3 g, 21.3 mmol) in anhydrous MeOH (70 mL) was treated with tosylmethyl isocyanide (4.4 g, 22.6 mmol) and K2CO3 (3.4 g, 24.4 mmol). After 2 h at reflux, the mixture was concentrated, diluted with saturated aqueous NaHCO3 and extracted with CH2Cl2. The organic layers were combined, dried (Na2SO4) and concentrated. Chromatography (SiO2, 40-50% EtOAc-hexanes gradient elution) provided 6 as a tan oil (3.1O g, 97%): 1H NMR (CDCl3, 400 MHz) δ 8.55-8.53 (m, IH), 7.90 (s, IH), 7.66 (td, J = 7.8, 1.8 Hz, IH), 7.62 (s, IH), 7.56 (d, J= 7.8 Hz, IH), 7.14 (ddd, J= 7.8, 4.9, 1.2 Hz, IH).
95%	With potassium carbonate In methanol Heating;
90%	With triethylamine; β‐cyclodextrin In lithium hydroxide monohydrate at 50℃; for 2h; Green chemistry;
90%	With potassium carbonate In methanol for 4h; Inert atmosphere; Reflux;	(1) At room temperature, 2-pyridinecarbaldehyde (6.29g, 34.7mmol) was dissolved in methanol (150mL), K2CO3 (9.6g, 69.5mmol) and A (8g, 38.2mmol) were added, and refluxed for 4h under nitrogen protection, After the completion of the reaction was detected by TLC, the reactant was concentrated under reduced pressure, the residue was dissolved in dichloromethane, washed with water, dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated in vacuo. The crude product was purified by silica gel column chromatography (PE:EA= 30:1) to obtain a colorless oil (compound B2-B20) in 90% yield;
80%	With potassium carbonate In methanol at 80℃; for 2h;
	With potassium carbonate In methanol
	With potassium carbonate In methanol

Reference： [1]Georgiades, Savvas N.; Rizeq, Natalia [Synlett, 2015, vol. 26, # 4, p. 489 - 493]
[2]Rizeq, Natalia; Georgiades, Savvas N. [European Journal of Organic Chemistry, 2016, vol. 2016, # 1, p. 122 - 131]
[3]Rizeq, Natalia; Georgiades, Savvas N [Molecules, 2017, vol. 22, # 12]
[4]Current Patent Assignee: SCRIPPS RESEARCH - WO2008/150492, 2008, A1 Location in patent: Page/Page column 41
[5]Pippel, Daniel J.; Mapes, Christopher M.; Mani, Neelakandha S. [Journal of Organic Chemistry, 2007, vol. 72, # 15, p. 5828 - 5831]
[6]Rahimzadeh, Golnaz; Kianmehr, Ebrahim; Mahdavi, Mohammad [Zeitschrift fur Naturforschung, B: Chemical Sciences, 2017, vol. 72, # 12, p. 923 - 926]
[7]Current Patent Assignee: FUJIAN MEDICAL UNIVERSITY - CN114014849, 2022, A Location in patent: Paragraph 0011; 0025
[8]Auvray, Marie; Franck, Xavier; Gallavardin, Thibault; Leleu, Stéphane; Mahuteau-Betzer, Florence; Mougeot, Romain; Oger, Samuel [European Journal of Organic Chemistry, 2022, vol. 2022, # 2]
[9]Saikachi; Kitagawa; Sasaki; Van Leusen [Chemical and Pharmaceutical Bulletin, 1979, vol. 27, # 3, p. 793 - 796]
[10]Wang, Lu; Yui, Joji; Wang, Qifan; Zhang, Yiding; Mori, Wakana; Shimoda, Yoko; Fujinaga, Masayuki; Kumata, Katsushi; Yamasaki, Tomoteru; Hatori, Akiko; Rotstein, Benjamin H.; Collier, Thomas Lee; Ran, Chongzhao; Vasdev, Neil; Zhang, Ming-Rong; Liang, Steven H. [ACS Chemical Neuroscience, 2016, vol. 7, # 1, p. 109 - 118]

2
[ 872-85-5 ]
[ 36635-61-7 ]
[ 70380-75-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	With Ambersep 900(OH) ion exchange resin In methanol; 1,2-dimethoxyethane for 2h; Reflux;	2.1.1. Preparation of heterocycle-5-oxazole 6 General procedure: A stirred mixture of heterocycle-carboxaldehyde 5(1.0 mmol) and p-toluene-sulfonylmethyl isocyanide (TosMIC)(1.1 mmol, 0.21 g) in 1:1 DME/MeOH (15 mL, both anhydrous) wasrefluxed with Ambersep 900(OH) ion exchange resin (2.0 g, exchangecapacity 1.18 meq/mL) for 2 h. The reaction mixture wasfiltered, the resin was washed by MeOH twice (2 5 mL), and thecombined filtrates were concentrated under reduced pressure togive the crude product, which was purified by column chromatography on silica gel (eluent: petroleum ether/acetone 4:1) to afford the pure compound 6.
99%	With Ambersep 900(OH) ion exchange resin In methanol for 2h; Reflux;	1.1.3 Preparation of substituted 5-(1H-indol-3-yl)oxazole (4). General procedure: A solution of substituted 1-(phenylsulfonyl)-1H-indole-3-carbaldehyde 3 (6.39 mmol) and TosMIC (11.69 mmol, 2.28 g) in 1:1 THF/MeOH (120 mL, both anhydrous) was refluxed with Ambersep 900(OH) ion exchange resin (21.0 g, exchange capacity 1.18 meq/mL) for 2 h. The reaction mixture was filtered, the resin was washed with acetone for several times, and the combined filtrates were evaporated under reduced pressure to remove the solvent, washed with water and extracted with dichloromethane (50 mL×3) and the extracts were dried over Na2SO4. Then the solvent was concentrated to give the crude product and purified by flash column chromatography using 12-17% acetone/petroleum ether (60-90 oC) as eluent to give the pure product 4.
	With potassium carbonate In methanol

	With potassium carbonate In methanol for 2h; Heating;
	With potassium carbonate In methanol for 3h; Heating / reflux;	18.a 4-Pyridinecarboxaldehyde (1.12 g, 10.5 mmol), tosylmethyl isocyanide (2.05 g, 10.5 mmol) and potassium carbonate (1.45 g, 10.5 mmol) were heated under reflux in methanol (30 mL) at 70 °C for 3 h. The solution was allowed to cool, and then evaporated. The residue was dissolved in chloroform, washed with saturated aqueous potassium carbonate, dried (MgSO4), filtered, and evaporated. The residue was purified by flash chromatography using a gradient of ethyl acetate in hexane to give the sub-title compound as a light yellow solid (1.10 g); m/z 147 (MH+).
	With potassium carbonate In methanol Reflux;	General procedure: To a solution of 3,4-bis(benzyloxy)benzaldehyde(3.0 g, 9.4 mmol, 1 eq) and p-toluenesulfonylmethylisocyanide (TosMIC) (2.0 g, 10.3 mmol,1.1 eq) in MeOH (47 mL) was added potassium carbonate (2.6 g, 18.9 mmol, 2 eq). Thereaction mixture was heated overnight in refluxing MeOH. The solvent was removed underreduced pressure and the crude product was agitated into water at 0 °C. A yellow precipitateappeared and was collected by filtration and dried under vacuum (3.1 g, 91 %).
	With potassium carbonate In methanol at 80℃; for 2h;

Reference： [1]Zhang, Ming-Zhi; Jia, Chen-Yang; Gu, Yu-Cheng; Mulholland, Nick; Turner, Sarah; Beattie, David; Zhang, Wei-Hua; Yang, Guang-Fu; Clough, John [European Journal of Medicinal Chemistry, 2017, vol. 126, p. 669 - 674]
[2]Zhang, Ming-Zhi; Mulholland, Nick; Seville, Anne; Hough, Gemma; Smith, Nicholas; Dong, Hong-Qiang; Zhang, Wei-Hua; Gu, Yu-Cheng [Tetrahedron, 2021, vol. 79]
[3]Saikachi; Kitagawa; Sasaki; Van Leusen [Chemical and Pharmaceutical Bulletin, 1979, vol. 27, # 3, p. 793 - 796]
[4]Pippel, Daniel J.; Mapes, Christopher M.; Mani, Neelakandha S. [Journal of Organic Chemistry, 2007, vol. 72, # 15, p. 5828 - 5831]
[5]Current Patent Assignee: ASTRAZENECA PLC - WO2006/65209, 2006, A1 Location in patent: Page/Page column 29
[6]Mahuteau-Betzer, Florence; Piguel, Sandrine [Tetrahedron Letters, 2013, vol. 54, # 24, p. 3188 - 3193]
[7]Auvray, Marie; Franck, Xavier; Gallavardin, Thibault; Leleu, Stéphane; Mahuteau-Betzer, Florence; Mougeot, Romain; Oger, Samuel [European Journal of Organic Chemistry, 2022, vol. 2022, # 2]

3
[ 123-19-3 ]
[ 36635-61-7 ]
[ 13310-75-3 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane; ethanol

Reference： [1]Oldenziel,O.H. et al. [Journal of Organic Chemistry, 1977, vol. 42, p. 3114 - 3118]

4
[ 57149-19-6 ]
[ 36635-61-7 ]
[ 38180-96-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide In <i>tert</i>-butyl alcohol

Reference： [1]Oldenziel,O.H.; van Leusen,A.M. [Tetrahedron Letters, 1972, p. 2777 - 2778]

5
[ 4746-97-8 ]
[ 38622-91-2 ]
[ 69947-09-7 ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium tert-butylate; In 1,2-dimethoxyethane; at 0 - 20℃;	The present invention will now be described in detail with reference to the foregoing,As shown above,In the present technical solution,The p-toluenesulfonyl methyl isocyanide of formula 1, and(1,4-dioxaspiro [4,5] decan-8-one)The contacting of the compounds shown is carried out in ethylene glycol dimethyl ether,And the molar ratio of p-toluenesulfonylmethyl isonitrile to the compound of formula 1 is 1: 1,The reaction temperature of the reaction system is 0-5 degrees Celsius,P-Methylphenylsulfonylmethylisonitrile (320 g, 1 mole)And compound 1 (156 g, 1 mole) were dissolved in ethylene glycol dimethyl ether (2000 ml)And the reaction system is cooled to 0-5 degrees;Potassium t-butoxide (224 g, 2 mol) was added in portions,Keep the system temperature does not exceed 5 degrees,After the addition was complete the system was slowly raised to room temperature with stirring,To the raw material reaction is complete;Saturated sodium chloride solution (3000 ml) was added,Extraction with methyl tert-butyl ether (500 ml * 2)Combine organic phase,dry,Spin dry,Distilled (100 C, 5 mm Hg) to give compound 2 (142 g, 85%) as a colorless oil,
71%	With potassium tert-butylate; In 1,2-dimethoxyethane; ethanol; at -13 - 5℃; for 0.666667h;	To a solution of Compound 58 (10.0 g, 64.0 mmol) in a mixture of 1,2-dimethoxyethane (218 ml)-ethanol (6.5 mL) was added p-toluenesulfonyl methyl isocyanide (16.3 g, 83.0 mmol), and the obtained reaction mixture was cooled to -13 C. Potassium t-butoxide (17.2 g, 154 mmol) was added thereto at 5 C. or less over 40 minutes. The reaction liquid was stirred under ice-cooling for one hour, and further stirred at room temperature for one hour, and the solvent was removed by distillation under reduced pressure. The residue was diluted with ethyl acetate, and then washed with water, and the solvent was removed by distillation under reduced pressure, followed by purification by silica gel chromatography to obtain Compound 67 (7.63 g, 45.6 mmol, 71%) as a colorless oily substance. Compound 67: 1H-NMR (CDCl3) delta: 1.57-1.67 (2H, m), 1.79-2.03 (5H, m), 2.66 (1H, s), 3.95 (4H, s).
69%		l,4-Dioxaspiro[4.5]decane-8-carbonitrileA solution of t-BuOK (22.8 g, 0.203 mol) in a 1: 1 mixture of t-BuOH and 1,2- dimethoxyethane (200 niL) was added to a solution of 1,4-cyclohexanedione monoethylene ketal (15.5 g, 0.099 mol) and tosylmethyl isocyanide (20.3 g, 0.104 mol) in dimethoxyethane (200 mL) at 00C. The reaction mixture was stirred for one hour at 00C, allowed to warm to ambient temperature and stirred for one extra hour. The reaction mixture was poured in water (500 mL). The product was extracted with hexane (3 x 200 mL) and ether (3 x 200 mL). The combined organics were dried with anhydrous Na2SO4 and the solvent was concentrated. The product was purified by flash chromatography on silica gel using EtOAc 40% in hexane as eluent to afford the title compound as a colorless liquid. Yield: 11.5 g (69%). 1H NMR (400 MHz, METHANOL-D4): delta 1.55 - 1.69 (m, 2 H), 1.70 - 1.80 (m, 2 H), 1.78 - 1.90 (m, 2 H), 1.90 - 2.05 (m, 2 H), 2.71 - 2.89 (m, 1 H), 3.86 - 3.98 (m, 4 H).

	With potassium tert-butylate; In 1,2-dimethoxyethane; tert-butyl alcohol; at 0 - 20℃; for 13h;	A solution of t-BuOK (147 g, 1.31 mol) in t-BuOH and DME (2.0 L, 1:1 v/v) was added dropwise to a 0-5 C. solution of 1,4-dioxaspiro[4.5]decan-8-one (100 g, 640 mmol) and TosMIC (131 g, 672 mmol) in DME (2.0 L), and the resulting mixture was stirred at 0-5 C. for 1 h before it was allowed to warm to rt over 12 h. After this time, the mixture was poured into water and then extracted three timed with MTBE. The organic layers were combined, washed with brine, dried with anhydrous Na2SO4, filtered, and then concentrated to afford the title compound, which was used in the next step without further purification.
	With potassium tert-butylate; In 1,2-dimethoxyethane; tert-butyl alcohol; at 0 - 20℃; for 13h;	A solution of t-BuOK (147 g, 1.31 mol) in t-BuOH and DME (2.0 L, 1:1 v/v) was added dropwise to a 0-5 C. solution of 1,4-dioxaspiro[4.5]decan-8-one (100 g, 640 mmol) and TosMIC (131 g, 672 mmol) in DME (2.0 L), and the resulting mixture was stirred at 0-5 C. for 1 h before it was allowed to warm to rt over 12 h. After this time, the mixture was poured into water and then extracted three timed with MTBE. The organic layers were combined, washed with brine, dried with anhydrous Na2SO4, filtered, and then concentrated to afford the title compound, which was used in the next step without further purification.

Reference： [1]Patent: CN106467477,2017,A .Location in patent: Paragraph 0025; 0026; 0027
[2]Synthesis,1992,p. 1080 - 1082
[3]Tetrahedron Letters,2000,vol. 41,p. 5589 - 5592
[4]Tetrahedron,2002,vol. 58,p. 1557 - 1563
[5]Patent: US9567330,2017,B2 .Location in patent: Page/Page column 67
[6]Patent: WO2007/13848,2007,A1 .Location in patent: Page/Page column 8
[7]Patent: US2019/382350,2019,A1 .Location in patent: Paragraph 0255
[8]Patent: US2019/382349,2019,A1 .Location in patent: Paragraph 0371-0372

6
[ 103-36-6 ]
[ 36635-61-7 ]
[ 64276-62-6 ]

Yield	Reaction Conditions	Operation in experiment
79%	With sodium hydride In diethyl ether; dimethyl sulfoxide; mineral oil at 20℃; for 3h; Inert atmosphere;
71.5%	With sodium hydride In diethyl ether; dimethyl sulfoxide for 2h; Ambient temperature;
	In tetrahydrofuran at 20℃; for 5h;	54 5 ml (47 mmol) of benzaldehyde and 13 g (57 mmol) of triethyl phosphonoacetate were dissolved in tetrahydrofuran, then 7.9 g (70 mmol) of potassium t-butoxide was added dropwise to the resulting solution at 0°C, followed by stirring for 2 hours. 7.9 g (70 mmol) of tosylmethyl isocyanide was added thereto and then stirred for 5 hours at room temperature. To the resulting solution, ethylacetate was added and the resulting solution was washed with ammonium chloride. This organic solution was dried over anhydrous magnesium sulfate, then the residue was purified by column chromatography to obtain 7.38 g of the titile compound in a yield of 70%. NMR : lH-NMR (CDCl3) 6 7. 51-7. 48 (3H, m), 7. 37-7. 33 (2H, m), 7. 29-7. 25 (1H, m), 6. 80-6. 79 (1H, m), 4.21 (2H, q, J=8Hz), 1.24 (2H, t, J=8Hz) Mass (EI) 216 (M++1)

	In diethyl ether; dimethyl sulfoxide
	With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 1.25h;

Reference： [1]Watt, Michael S.; Booker-Milburn, Kevin I. [Organic Letters, 2016, vol. 18, # 21, p. 5716 - 5719]
[2]Massa; Di Santo; Mai; Botta; Artico; Panico; Simonetti [Il Farmaco, 1990, vol. 45, # 7-8, p. 833 - 846]
[3]Current Patent Assignee: LG CHEM CO.,LTD. - WO2005/40127, 2005, A1 Location in patent: Page/Page column 132
[4]Syamaiah, Kaveri; Mallikarjuna Reddy, Guda; Padmavathi, Venkatapuram; Padmaja, Adivireddy [Medicinal Chemistry Research, 2014, vol. 23, # 7, p. 3287 - 3297]
[5]Su, Youla; Zhou, Haipin; Chen, Jiaxuan; Xu, Jinyi; Wu, Xiaoming; Lin, Aijun; Yao, Hequan [Organic Letters, 2014, vol. 16, # 18, p. 4884 - 4887]

7
[ 19398-53-9 ]
[ 36635-61-7 ]
1-(1-Isocyano-2,4-dimethyl-cyclobutanesulfonyl)-4-methyl-benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride In diethyl ether; dimethyl sulfoxide

Reference： [1]Hanack,M.; Auchter,G. [Journal of the American Chemical Society, 1985, vol. 107, p. 5238]

8
[ 2396-84-1 ]
[ 36635-61-7 ]
[ 85960-29-8 ]

Yield	Reaction Conditions	Operation in experiment
80%	With sodium hydride In diethyl ether; dimethyl sulfoxide at 20℃; for 3h;
52%	With sodium hydride In diethyl ether; dimethyl sulfoxide at 0 - 20℃; for 3h;
45%	With sodium hydride In diethyl ether; dimethyl sulfoxide; mineral oil at 0 - 20℃; for 3h; Inert atmosphere;

Reference： [1]Magnus, Philip; Gallagher, Timothy; Schultz, James; Or, Yat-Sun; Ananthanarayan, T.P. [Journal of the American Chemical Society, 1987, vol. 109, # 9, p. 2706 - 2711] Magnus; Or [Journal of the Chemical Society. Chemical communications, 1983, vol. No. 1, # 1, p. 26 - 27]
[2]De Leon, Christine Y.; Ganem, Bruce [Tetrahedron, 1997, vol. 53, # 23, p. 7731 - 7752]
[3]Cooper, Stephen P.; Booker-Milburn, Kevin I. [Angewandte Chemie - International Edition, 2015, vol. 54, # 22, p. 6496 - 6500]

9
[ 2396-84-1 ]
[ 36635-61-7 ]
1-Benzenesulfonyl-4-((E)-propenyl)-1H-pyrrole-3-carboxylic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With lithium hexamethyldisilazane In tetrahydrofuran

Reference： [1]Magnus, Philip; Gallagher, Timothy; Schultz, James; Or, Yat-Sun; Ananthanarayan, T.P. [Journal of the American Chemical Society, 1987, vol. 109, # 9, p. 2706 - 2711]

10
[ 4541-32-6 ]
[ 36635-61-7 ]
[ 153580-00-8 ]

Yield	Reaction Conditions	Operation in experiment
50%	With potassium <i>tert</i>-butylate In methanol; dimethyl sulfoxide Ambient temperature;

Reference： [1]Peterson, Eileen M.; Xu, Kun; Holland, Katherine D.; McKeon, Ann C.; Rothman, Steven M.; et al. [Journal of Medicinal Chemistry, 1994, vol. 37, # 2, p. 275 - 286]

11
[ 5766-74-5 ]
[ 36635-61-7 ]
[ 74730-75-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In methanol for 4h; Heating; Yield given;

Reference： [1]Yamada, Naotaka; Kuwano, Eiichi; Kikuchi, Masamichi; Eto, Morifusa [Bioscience, Biotechnology and Biochemistry, 1992, vol. 56, # 12, p. 1943 - 1948]

12
[ 36635-61-7 ]
[ 95202-45-2 ]
[ 60011-57-6 ]

Yield	Reaction Conditions	Operation in experiment
69%	With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane

Reference： [1]Merour, J. Y.; Buzas, A. [Synthetic Communications, 1988, vol. 18, # 18, p. 2331 - 2336]

13
[ 38622-91-2 ]
[ 105-07-7 ]
[ 87150-13-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate; In methanol; at 20℃; for 1.33333h;	4-(oxazol-5-yI)benzonitrile A mixture of 4-formylbenzonitrile (commercially available from for example Aldrich) (5.32 g, 41 mmol), l-((isocyanomethyl)sulfonyl)-4-methylbenzene (commercially available from for example Aldrich) (8.83 g, 45 mmol) and potassium carbonate (7.3 g, 53 mmol) in methanol (200 mL) was stirred at ambient temperature for 80 minutes. The mixture was then evaporated to dryness; the residue was treated with saturated aqueous sodium bicarbonate (100 mL) and extracted with dichloromethane (3 x 100 mL). The combined organics were washed with brine (75 mL), passed through a hydrophobic frit and then evaporated to dryness to afford the title compound (7.19 g, 42 mmol, quantitative). LCMS RT= 0.48 min, ES+ve m/z 171 [M+H]+.
100%	With potassium carbonate; In methanol; at 20℃; for 1.33333h;	A mixture of 4-formylbenzonitrile (commercially available from for example Aldrich) (5.32 g, 41 mmol), 1-((isocyanomethyl)sulfonyl)-4-methylbenzene (commercially available from for example Aldrich) (8.83 g, 45 mmol) and potassium carbonate (7.3 g, 53 mmol) in methanol (200 mL) was stirred at ambient temperature for 80 minutes. The mixture was then evaporated to dryness; the residue was treated with saturated aqueous sodium bicarbonate (100 mL) and extracted with dichloromethane (3×100 mL). The combined organics were washed with brine (75 mL), passed through a hydrophobic fit and then evaporated to dryness to afford the title compound (7.19 g, 42 mmol, quantitative). LCMS RT=0.48 min, ES+ve m/z 171 [M+H]+.
100%	With potassium carbonate; In methanol; at 20℃; for 1.33333h;	4- (Oxazol- 5-yl)benzonitrile A mixture of 4-formylbenzonitrile (commercially available from for example Aldrich) (5.32 g, 41 mmol), l-((isocyanomethyl)sulfonyl)-4-methylbenzene (commercially available from for example Aldrich) (8.83 g, 45 mmol) and potassium carbonate (7.3 g, 53 mmol) in methanol (200 mL) was stirred at ambient temperature for 80 minutes. The mixture was then evaporated to dryness; the residue was treated with saturated aqueous sodium bicarbonate (100 mL) and extracted with dichloromethane (3 x 100 mL). The combined organics were washed with brine (75 mL), passed through a hydrophobic frit and then evaporated to dryness to afford the title compound (7.19 g, 42 mmol, quantitative). LCMS RT= 0. 75min, ES+ve m/z 171 [M+H]+.

97%	With potassium carbonate; In methanol; for 1h;Heating / reflux;	-Preparation of 4-Oxazol-5-yl-benzonitrile; To a solution of 4-Formyl-benzonitrile (5 g, 38.17 mmol) and tosylmethyl isocyanide (TosMIC) (from Aldrich, 8.33 g, 42 mmol) in MeOH (200 mL) was added K2CO3 (6.85 g, 49.62 mmol) and the mixture was stirred at reflux for Ih. The solvent was then evaporated and saturated aqueous NaHCC>3 was added. The resultant suspension was extracted with dichloromethane (3x100 mL). The combined organic layers were washed with brine (30 mL), dried over anhydrous MgSO4 and concentrated to leave a yellow <n="9"/>solid. Trituration with heptane afforded a solid that was collected by filtration and dried under vacuum to give the title compound (6.3 g, 97%). m.p. = 1400C 1H NMR (DMSO-/) delta = 7.91-7.98 (5H, m), 8.58 (IH, s).
84%	With potassium carbonate; In methanol; for 1.5h;Reflux;	Compound 1: 4-(oxazol-5-yl)benzonitrile To a 500 mL round-bottom flask was added 4-cyanobenzaldehyde (5.00 g, 38.1 mmol), methanol (200 mL), p-toluene sulfonylmethyl isocyanide (8.33 g, 42.66 mmol), followed by potassium carbonate (6.85 g, 49.56 mmol). The reaction mixture was stirred at reflux for about 1.5 hour and followed by TLC. The solvent was then evaporated and saturated aq.NaHCO3 was added. The resultant suspension was extracted with CH2Cl2 (3*100 mL). Combined organic layers were washed with brine, dried (anhydrous Na2SO4), and concentrated to leave a yellow solid. Trituration with hexane afforded a solid which was collected by filtration and dried. Crude product was further purified by re-crystallization using hot-CH2Cl2 and cold-hexane to afford title compound 1 (5.48 g, 84% yield). MS (ES) m/z 171 (M+H+).
75%	With potassium carbonate; at 80℃; for 1.5h;	General procedure: To a solution of p-anisaldehyde (1.22 mL, 10.0 mmol) in MeOH (25 mL) were added K2CO3 (1.52 g, 11.0 mmol) and TosMIC (1.08 g, 5.50mmol). The reaction mixture was stirred for 1.5 h at 80 C, cooled down to rt, quenched with H2O, and diluted with EtOAc. After removal of the organic layer, the aqueous layer was extracted with EtOAc. The organic layer was combined, dried over Na2SO4, filtered, and concentrated in vacuo. Flash chromatography (3:1 hexanes/EtOAc) afforded 5-(4-methoxyphenyl)oxazole (1) (955 mg, 99%) as a pale yellow solid
1 g	With potassium carbonate; In methanol; at 20℃; for 1.5h;	Step 1: 1. Synthesis of 4-(l,3-oxazol-5-yl)benzonitrile (S) [0428] To a stirred solution of 4-formylbenzonitrile (R, 1.0 g, 7.63 mmol) in methanol(40 mL) was added [[(4-methylbenzene)sulfonyl]methyl](methyliumylidyne)azanuide (1.6 g, 8.40 mmol) and potassium carbonate (1.4 g, 9.91 mmol), the resulting mixture was stirred at rt for 1.5 h. The bulk of solvent was then removed under reduced pressure. The residue was diluted with saturated aqueous sodium bicarbonate (20 mL) and was extracted with dichloromethane (30 mL x 3). The organic layers were combined, washed with brine (30 mL), dried over anhydrous sodium sulfate and concentrated under vacuum to give a crude product, which was purified by re-crystallization using dichloromethane and hexane to give S (1.0 g) as a white solid. 1H NMR (400 MHz, DMSO) delta 8.56 (s, 1H), 7.97-7.83 (m, 5H); LC-MS (ES+): m/z 170.95 [MH+], tR= 0.79 min (2.0 minute run).

Reference： [1]Patent: WO2013/106646,2013,A2 .Location in patent: Page/Page column 185-186
[2]Patent: US2014/356322,2014,A1 .Location in patent: Paragraph 0420
[3]Patent: WO2015/867,2015,A1 .Location in patent: Page/Page column 47
[4]Patent: WO2007/131953,2007,A1 .Location in patent: Page/Page column 7-8
[5]Zeitschrift fur Naturforschung, B: Chemical Sciences,2017,vol. 72,p. 923 - 926
[6]Patent: US2012/302578,2012,A1 .Location in patent: Page/Page column 20
[7]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 313 - 316
[8]Liebigs Annalen der Chemie,1984,p. 641 - 648
[9]Angewandte Chemie - International Edition,2012,vol. 51,p. 6993 - 6997
[10]Angewandte Chemie - International Edition,2013,vol. 52,p. 4457 - 4461
Angew. Chem.,2013,vol. 125,p. 4553 - 4557,5
[11]Journal of Organic Chemistry,2013,vol. 78,p. 11045 - 11052
[12]ACS Medicinal Chemistry Letters,2014,vol. 5,p. 23 - 28
[13]Journal of Medicinal Chemistry,2014,vol. 57,p. 8657 - 8663
[14]Patent: WO2016/118666,2016,A1 .Location in patent: Paragraph 0426; 0427; 0428

14
[ 36635-61-7 ]
[ 623-91-6 ]
[ 41969-71-5 ]

Yield	Reaction Conditions	Operation in experiment
71%	With potassium-t-butoxide In tetrahydrofuran at 0 - 25℃; for 2.33h; Inert atmosphere;	2.2 Synthesis of pyrrole-3,4-dicarboxylic acid diethyl ester (2) Potassium tert-butoxide (7.09 g, 60.0 mmol) was suspended in anhydrous THF (90.0 mL) under N2 atmosphere and stirred at 0 °C. A solution of diethyl fumarate (5.00 mL, 5.26 g, 30.0 mmol) and p-toluenesulfonylmethylisocyanide (TosMIC) (5.98 g, 30.0 mmol), in anhydrous THF (60 mL), was added dropwise for 20 min. After the addition, the mixture was stirred for 2 h at 25 °C. An aqueous solution of HCl (pH = 5-6, 100 mL) was added and the mixture was extracted with EtOAc (2 × 100 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated almost to dryness. The mixture was gently heated with a heat gun until the entire solid became soluble. The solution was allowed to cool to 25 °C and then taken to 0 °C for about 30 min. The solid obtained was collected by removing the EtOAc with a Pasteur pipette and the organic phase (EtOAc with remaining compound 2) was saved. The solid was crystallized twice yielding pyrrole 2 as white crystals (3.14 g). The EtOAc layers were concentrated and purified by silica-flash column chromatography using toluene/EtOAc (7:3) as eluent, obtaining a further 1.35 g of 2. The product 2 was obtained in 71% yield (4.49 g, 21.3 mmol). 1H NMR (CDCl3, 400.15 MHz): δ (ppm): 1.34 (t, J = 7.1 Hz, 6H, H-33, H-43); 4.30 (q, J = 7.1 Hz, 4H/H-32, H-42); 7.36 (d, J = 2.9 Hz, 2H, H-2, H-5); 9.39 (brs, 1H, H-1). 13C NMR (CDCl3, 100.62 MHz): δ(ppm): 14.3 (C-33, C43); 60.3 (C-32, C-42); 115.9 (C-3, C-4); 125.7 (C-2, C-5); 164.1 (C-31, C-41). HRMS (ESI-TOF): calc. for [M+H]+,C10H14NO4+, 212.0917; found: 212.0921.
63%	With 18-crown-6 ether; potassium-t-butoxide In tetrahydrofuran
57%	With potassium-t-butoxide In tetrahydrofuran at 0 - 20℃; for 5h; Schlenk technique; Inert atmosphere; Cooling with ice;

53%	With sodium hydride In diethyl ether; dimethyl sulfoxide; mineral oil at 20℃; for 5h; Inert atmosphere;
44%	With potassium-t-butoxide In tetrahydrofuran for 2h;
	With potassium-t-butoxide In tetrahydrofuran
4.6 g (44%)	With sodium chloride In tetrahydrofuran	39 Diethyl pyrrole-3,4-dicarboxylate EXAMPLE 39 Diethyl pyrrole-3,4-dicarboxylate Tosylmethyl isocyanide (9.8 g, 50 mmol), diethyl fumarate (8.2 mL, 50 mmol) and dry THF (1000 mL) were added dropwise to a stirred suspension of potassium t-butoxide (11.2 g, 100 mmol) and THF (150 mL). The mixture was stirred for 2 hours, saturated NaCl (500 mL) was added, and the mixture was extracted with THF (2*250 mL). The organic layers were dried (Na2 SO4), filtered and concentrated in vacuo to give a solid. The solid was recrystallized from MeOH to give the title compound 4.6 g (44%) (mp 148-149° C.). 1 H NMR (DMSO) δ 1.22 (t, 3H, CH3), 4.18 (q, 2H, CH2), 7.39 (s, 2H, ArH), 11.8 (bs, 1H, NH).
	With 18-crown-6 ether; potassium-t-butoxide In tetrahydrofuran
	With potassium-t-butoxide Schlenk technique;

Reference： [1]De Assis, Francisco F.; De Souza, Juliana M.; Assis, Beatriz H.K.; Brocksom, Timothy J.; De Oliveira, Kleber T. [Dyes and Pigments, 2013, vol. 98, # 1, p. 153 - 159]
[2]Bush, Linda C.; Heath, Richard B.; Feng, Xu Wu; Wang, Patricia A.; Maksimovic, Ljiljana; Song, Anne In; Chung, Wen-Sheng; Berinstain, Alain B.; Scaiano; Berson, Jerome A. [Journal of the American Chemical Society, 1997, vol. 119, # 6, p. 1406 - 1415]
[3]Amanullah, Sk; Saha, Paramita; Dey, Abhishek [Journal of the American Chemical Society, 2021, vol. 143, # 34, p. 13579 - 13592]
[4]Chen, Boyang; Chen, Chih-Yuan; Jiang, Jianbing; Jing, Haoyu; Lindsey, Jonathan S.; Liu, Sijia; Nalaoh, Phattananawee; Rong, Jie; Vairaprakash, Pothiappan; Wang, Pengzhi [New Journal of Chemistry, 2022, vol. 46, # 12, p. 5534 - 5555]
[5]Arnold, Dennis P.; Nitschinsk, Lisa J.; Kennard, Colin H. L.; Smith, Graham [Australian Journal of Chemistry, 1991, vol. 44, # 2, p. 323 - 330]
[6]Donohoe, Timothy J.; Harji, Rakesh R.; Cousins, Rick P. C. [Chemical Communications, 1999, # 2, p. 141 - 142]
[7]Current Patent Assignee: IONIS PHARMACEUTICALS - US6107482, 2000, A
[8]Saha, Indrajit; Park, Kyung Hwa; Han, Mina; Kim, Sung Kuk; Lynch, Vincent M.; Sessler, Jonathan L.; Lee, Chang-Hee [Organic Letters, 2014, vol. 16, # 20, p. 5414 - 5417]
[9]Hale, Benjamin J.; Elshobaki, Moneim; Gebhardt, Ryan; Wheeler, David; Stoffer, Jon; Tomlinson, Aimée; Chaudhary, Sumit; Jeffries-EL, Malika [Polymer, 2017, vol. 109, p. 85 - 92]

15
[ 36635-61-7 ]
[ 764-42-1 ]
[ 125666-25-3 ]

Yield	Reaction Conditions	Operation in experiment
79%	With sodium hydride In N,N-dimethyl-formamide at 0 - 5℃; for 0.25h;

Reference： [1]Magnus, Philip; Danikiewicz, Witold; Katoh, Tadashi; Huffman, John C.; Folting, Kirsten [Journal of the American Chemical Society, 1990, vol. 112, # 6, p. 2465 - 2468]

16
[ 36635-61-7 ]
[ 81879-64-3 ]
[ 141380-18-9 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 2831 - 2840

17
[ 345-69-7 ]
[ 36635-61-7 ]
[ 164927-40-6 ]

Yield	Reaction Conditions	Operation in experiment
84%	With methanol; potassium <i>tert</i>-butylate In dimethyl sulfoxide for 17h; Ambient temperature;

Reference： [1]Mbela; Poupaert; Cumps; Moussebois; Haemers; Borloo; Dumont [Journal of Pharmacy and Pharmacology, 1995, vol. 47, # 3, p. 237 - 242]

18
[ 36635-61-7 ]
(E)-1,3-di(4-chlorophenyl)-2-propen-1-one [ No CAS ]
[ 170939-22-7 ]

Yield	Reaction Conditions	Operation in experiment
40%	With sodium hydride In diethyl ether; dimethyl sulfoxide for 0.5h; Ambient temperature;

Reference： [1]Artico; Di Santo; Costi; Massa; Retico; Artico; Apuzzo; Simonetti; Strippoli [Journal of Medicinal Chemistry, 1995, vol. 38, # 21, p. 4223 - 4233]

19
[ 36635-61-7 ]
[ 133031-38-6 ]
[ 170939-29-4 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium hydride In diethyl ether; dimethyl sulfoxide for 0.0833333h; Ambient temperature;

Reference： [1]Artico; Di Santo; Costi; Massa; Retico; Artico; Apuzzo; Simonetti; Strippoli [Journal of Medicinal Chemistry, 1995, vol. 38, # 21, p. 4223 - 4233]

20
[ 14174-77-7 ]
[ 36635-61-7 ]
(1RS,8aRS)-1,2,3,5,6,7,8,8a-octahydroindolizine-1-carbonitrile [ No CAS ]
(1S,8aR)-Octahydro-indolizine-1-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With ethanol; potassium <i>tert</i>-butylate In 1,2-dimethoxyethane at 15 - 40℃;

Reference： [1]Wyman, Paul A.; Gaster, Laramie M.; King, Frank D.; Sutton, Jonathon M.; Ellis, Elizabeth S.; Wardle, Kay A.; Young, Timothy J. [Bioorganic and Medicinal Chemistry, 1996, vol. 4, # 2, p. 255 - 261]

21
[ 1003-29-8 ]
[ 36635-61-7 ]
[ 70380-76-6 ]

Yield	Reaction Conditions	Operation in experiment
82%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran for 2h; Ambient temperature;
76%	Stage #1: [(p-methylphenyl)sulfonylmethyl]isonitrile With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran Inert atmosphere; Stage #2: 2-pyrrole aldehyde In tetrahydrofuran at 20℃; for 2h;	106 PREPARATION 106 3-[(4-Methylphenyl)sulfonyl]pyrrolo[1 ,2-c]pyrimidine PREPARATION 106 3-[(4-Methylphenyl)sulfonyl]pyrrolo[1 ,2-c]pyrimidine p-Toluenesulfonylmethyl isocyanide (1 1 .3 g, 58 mmol) and 1 ,8-diazabicycloundec-7- ene (DBU) (8.7 ml, 0.06 mol) were dissolved in 120 ml tetrahydrofuran under nitrogen atmosphere. A solution of 1 /-/-pyrrole-2-carbaldehyde (5 g, 0.05 mol) in 200 ml tetrahydrofuran was added and the mixture was stirred at room temperature for 2 h. The mixture was neutralised with glacial acetic acid and evaporated under reduced pressure. The residue triturated with dichloromethane and the solid was collected by filtration, washed with dichloromethane and dried in vacuo to give 10.9 g (40 mmol, 76%) of the title compound as a white solid. Purity 100%. 1 H NMR (300 MHz, CHLOROFORM-d) δ ppm 8.73 (s, 1 H), 8.25 (s, 1 H), 7.94 (d, J=7.97 Hz, 2 H), 7.50 (d, J=2.75 Hz, 1 H), 7.32 (d, J=7.97 Hz, 2 H), 7.03 (t, J=3.43 Hz, 1 H), 6.83 (d, J=3.02 Hz, 1 H), 2.41 (s, 3 H). UPLC/MS (3 min) retention time 1 LRMS: m/z 273 (M+1 ).
76%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 20℃; for 2h; Inert atmosphere;	106 PREPARATION 106 3-[(4-Methylphenyl)sulfonyl]pyrrolo[1,2-c]pyrimidine p-Toluenesulfonylmethyl isocyanide (11.3 g, 58 mmol) and 1,8-diazabicycloundec-7-ene (DBU) (8.7 ml, 0.06 mol) were dissolved in 120 ml tetrahydrofuran under nitrogen atmosphere. A solution of 1H-pyrrole-2-carbaldehyde (5 g, 0.05 mol) in 200 ml tetrahydrofuran was added and the mixture was stirred at room temperature for 2 h. The mixture was neutralised with glacial acetic acid and evaporated under reduced pressure. The residue triturated with dichloromethane and the solid was collected by filtration, washed with dichloromethane and dried in vacuo to give 10.9 g (40 mmol, 76%) of the title compound as a white solid. Purity 100%. [0671] 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 8.73 (s, 1 H), 8.25 (s, 1 H), 7.94 (d, J=7.97 Hz, 2 H), 7.50 (d, J=2.75 Hz, 1 H), 7.32 (d, J=7.97 Hz, 2 H), 7.03 (t, J=3.43 Hz, 1 H), 6.83 (d, J=3.02 Hz, 1 H), 2.41 (s, 3 H). [0672] UPLC/MS (3 min) retention time 1.56 min. [0673] LRMS: m/z 273 (M+1).

Reference： [1]Minguez, Jose M.; Vaquero, Juan J.; Garcia-Navio, Jose L.; Alvarez-Builla, Julio [Tetrahedron Letters, 1996, vol. 37, # 24, p. 4263 - 4266]
[2]Current Patent Assignee: ALMIRALL SA - WO2013/10880, 2013, A1 Location in patent: Page/Page column 131
[3]Current Patent Assignee: ALMIRALL SA - EP2548876, 2013, A1 Location in patent: Paragraph 0670-0673

22
[ 20754-20-5 ]
[ 36635-61-7 ]
[ 188524-66-5 ]

Yield	Reaction Conditions	Operation in experiment
64%	With sodium hydride In diethyl ether; dimethyl sulfoxide for 1h; Heating;

Reference： [1]Pavri; Trudell [Journal of Organic Chemistry, 1997, vol. 62, # 8, p. 2649 - 2651]

23
[ 36635-61-7 ]
[ 81124-48-3 ]
[ 188524-69-8 ]

Yield	Reaction Conditions	Operation in experiment
64%	With sodium hydride In diethyl ether; dimethyl sulfoxide for 1h; Heating;

Reference： [1]Pavri; Trudell [Journal of Organic Chemistry, 1997, vol. 62, # 8, p. 2649 - 2651]

24
[ 1072-72-6 ]
[ 36635-61-7 ]
[ 195503-40-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane; <i>tert</i>-butyl alcohol at 0 - 30℃;	29 Reference Example 29; tetrahydro-2H-thiopyran-4-carbonitrile; [Show Image] Tetrahydro-4H-thiopyran-4-one (10.00 g) and p-toluenesulfonylmethyl isocyanide (18.49 g) were dissolved in DME (400 mL). A solution of potassium tert-butoxide (19.32 g) in tert-butanol (150 mL) was added thereto at 0°C, and the mixture was stirred at room temperature for 3 hr. The mixture was diluted with diethyl ether, washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine (twice), dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography [eluent; ethyl acetate] to give the title compound (10.93 g, yield 100%) as a brown transparent oil. 1H NMR (300 MHz, CDCl3) δ: 2.03-2.22 (4 H, m), 2.52-2.65 (2 H, m), 2.77-2.93 (3 H, m).
100%	With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane; <i>tert</i>-butyl alcohol at 20℃; for 3h;	29a; 29b Tetrahydro-2H-thiopyran-4-carbonitrile To a solution of dihydro-2H-thiopyran-4(3H)-one (10.0 g, 86.2 mmol) and tosylmethyl isocyanide (18.68 g, 94.82 mmol) in 1,2-dimethoxyethane (250 mL) was added a solution of t-BuOK (19.31 g, 172.4 mmol) in 1:1 t-BuOH/1,2-dimethoxyethane (200 mL). The mixture was stirred at RT for 3 h, then diluted with EtOAc and washed with 5% aq. NaHCO3, dried over Na2SO4, and concentrated under reduced pressure to give the title compound as a brown oil (10.93 g, 100%). MS (ES+): C6H9NS requires: 127, found: 128 [M+H]+.
93%	With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane; <i>tert</i>-butyl alcohol at 20℃; for 3h;	13 Example 13: Synthesis [OF 6- (4-BENZYLOXY-PHENYL)-7- (TETRAHYDRO-THIOPYRAN-4-YL)-3- (IH-] tetrazol-5-yl) -pyrazolo [1, 5-a] pyrimidine According to a modification of a literature procedure (Helv. Chim. Acta 1997, [80,] 1528) to an ice cold solution of 2.0 g (17.2 mmol) of tetrahydro-thiopyran-4-one, and 3.69 g (18.9 mmol) [OF 1-ISOCYANOMETHANESULFONYL-4-METHYL-BENZENE] in 100 mL of 1,2- dimethoxyethane (DME) was added 34.4 mL (34.4 mmol) [OF POTASSIUM T-BUTOXIDE (1] M solution in t-butanol), and the resulting mixture was stirred at rt for 3 h. The reaction mixture was diluted with diethyl ether, washed with saturated sodium bicarbonate solution, dried over sodium sulfate and concentrated to give 2.05 g (93% yield) of desired [TETRAHYDRO-THIOPYRAN-4-] [CARBONITRILE] as indicated by 1H NMR. A solution of 1.97 g (15.5 mmol) [OF TETRAHYDRO-THIOPYRAN-4-CARBONITRILE] in 5 mL of ethanol (EtOH) was added to a solution of 6.2 g (155 mmol) of sodium hydroxide (NaOH) in 30 mL of EtOH and 15 mL of water, and the resulting mixture was heated at reflux for 4 h. The reaction mixture was cooled in an ice bath, acidified with concentrated hydrochloric acid to pH=2, and then concentrated to give a precipitate which was filtered to afford 1.36 g (60%) of desired [TETRAHYDRO-THIOPYRAN-4-CARBOXYLIC ACID] as a brown crystalline solid as indicated by [H NMR.] To an ice cold solution of [1.] [36 G] (9.32 mmol) tetrahydro-thiopyran-4-carboxylic acid in 25 [ML] of dichloromethane (DCM) was added [DROPWISE 1. 1 ML (12.] 6 mmol) of oxalyl chloride, and the resulting mixture was stirred at [0 C FOR 2 H. THEN 2, UL OF DIMETHYLFORMAMIDE] (DMF cat) was [ADDED, AND THE REACTION MIXTURE WAS STIRRED AT RT FOR 2 H, AND CONCENTRATED TO GIVE] [1.] 43 g [93%)] [OF DESIRED TETRAHYDRO-THIOPYRAN-4-CARBONYL] chloride as a brown oil as indicated by 1H NMR. The product was used without any further purification in the next step toward the preparation of 6-(4-Benzyloxy-phenyl)-7-(tetrahydro-thiopyran-4-yl)-3-(1H-tetrazol-5-yl)- pyrazolo[1,5-a]pyrimidine (below,entry 375)

85%	With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane; <i>tert</i>-butyl alcohol for 3h; Ambient temperature;
50.7%	With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane; <i>tert</i>-butyl alcohol at 0 - 20℃; for 3h;	2 A cold (ice water bath) solution of tetrahydro-2H-thiopyran-4-one (3.57 g, 30.7 mmol) and tosylmethylisocyanide (6.61 g, 33.8 mmol) in DME (125 ml) was treated with a suspension of potassium t-butoxide (6.93 g, 61.8 mmoles) in t-butyl alcohol (100 ml). The reaction mixture was stirred at room temperature for 3 hours, and then diluted with ether (250 ml). The mixture was successively washed with water and brine, then dried over sodium sulfate, filtered, and concentrated. The crude product was purified by short path distillation under high vacuum to give nitrile 1 as colorless oil (1.98 g, 50.7%). A solution of nitrile 1 (1.0 g, 7.9 mmoles) in ethanol (15 ml) was cooled in an ice bath. Hydrogen chloride gas was bubbled into the solution until saturation. The reaction mixture was then stirred at room temperature for 2 hours. Water (5 ml) was added and stirring was continued at room temperature for 2.5 hours, at 60° C. for 4 hours, and finely at room temperature for 12 hours. The reaction mixture was concentrated and partitioned between water and ethyl acetate. The organic layer was successively washed with water and brine, then dried over sodium sulfate, filtered, and concentrated to afford ester 2 (539 mg, 40%). A solution of ester 2 (539 mg, 3.1 mmoles) and hydrazine monohydrate (3 ml, 61.9 mmoles) in MeOH (1 ml) was heated in a microwave oven at 160° C. for 10 min. Concentration of the reaction mixture under reduced pressure afforded hydrazide 3 (481 mg, 97%). A solution of 3 (481 mg, 3 mmoles) in acetone (2 ml) was heated in a microwave oven at 120° C. for 20 min. The acetone was removed under vacuum and the residue was dissolved in TFA (8 ml) and treated with triethylsilane (0.874 ml, 5.47 mmol) at 60° C., for 18 hours. The reaction mixture was concentrated and the residue was partitioned between saturated sodium bicarbonate solution and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated to afford the desired product (302 mg, 55%).
26%	With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane; <i>tert</i>-butyl alcohol at 0 - 20℃; for 3h; Inert atmosphere;	Tetrahydro-2H-thiopyran-4-carbonitrile (S4) A mixtureof tetrahydro-4H-thiopyran-4-one (S3) (3.00 g, 25.8 mmol) and toluenesulfonylmethyl isocyanide (TosMIC, 5.55 g, 28.4 mmol) in dimethoxyethane (105 mL) was cooled to 0 °C and a solution of t-BuOK (5.79 g, 51.6 mmol) in t-BuOH (52 mL) was added to the reaction mixture in a dropwise manner. The mixture was then allowed to warm to room temperature and stirred for 3 h before dilution with Et2O. The organic layer was washed with sat. aq. NaHCO3, dried over MgSO4, and evaporated. The residue was purified by column chromatography (AcOEt/hexane = 1/10 to 1/4) to afford tetrahydro-2H-thiopyran-4-carbonitrile (S4) (836 mg, 6.57 mmol, 26%) as a yellow oil.1H-NMR (400 MHz, CDCl3) δ: 2.89-2.79 (m, 3H), 2.60 (dd,J = 7.2, 3.9 Hz, 1H), 2.56 (dd, J = 7.7, 3.4 Hz, 1H), 2.19-2.05 (m, 4H). 13C-NMR (100 MHz, CDCl3) δ: 121.1, 30.0, 27.8, 25.8. IR (neat, cm-1): 2917, 2240, 1712, 1431. MS m/z: 127 ([M]+), 127 (100%). HRMS (EI): Calcd for C6H9NS 127.0456, found: 127.0467.
	With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane; <i>tert</i>-butyl alcohol at 20℃; for 3h;	68 A cold (ice water bath) solution of tetrahydro-4H-thiopyran-4-one (5 g, 43 mmol) and tosylmethylisocyanide (9.24 g, 47.3 mmol) in DME (200 ml) was treated with a suspension of potassium tert-butoxide (9.66 g, 86 mmoles) in tert-butyl alcohol (200 ml). The reaction mixture was stirred at room temperature for 3 hours, and then diluted with ether. The mixture was successively washed with water and brine, then dried over sodium sulfate, filtered, and concentrated. The crude product was purified by short path distillation under high vacuum to give the nitrile as colorless oil (3.06 g). A portion of this material (2 g, 15.7 mmol) was dissolved in 1M borane/THF (80 ml, 80 mmol) and stirred at room temperature for 48 h. Excess borane was quenched by adding methanol (room temperature, 1 h), and the mixture was concentrated to dryness. The residue was dissolved in 4N HCl/dioxane, stirred at room temperature for 1 h and then concentrated under reduced pressure. The solid residue was triturated with ether and collected by suction filtration. A suspension of this material (2.35 g, 14 mmol) in THF (100 ml) was treated with 1N NaOH (14 ml, 14 mmol) at room temperature for 1/2 h. The THF was removed by distillation and the aqueous solution was saturated with NaCl then extracted with dichloromethane. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was treated with acetic acid (0.48 ml, 8.5 mmol) to provide, after drying in a vacuum oven, 2-(tetrahydro-thiopyran-4-yl)-methylammonium acetate (1.30 g).
	With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane; <i>tert</i>-butyl alcohol at 0 - 20℃; for 3h;	II.A II: Toluene-4-sulfonic acid 1 ,1-dioxo-hexahvdro-1-thiopyran-4-ylmethyl ester intermediate Step A: Tetrahvdro-thiopyran-4-carbonitrile A mixture of tetrahydro-thiopyran-4-one (75 g, 646 mmol) and toluenesulfonyl- methyl isocyanide (138.6 g, 710 mmol) in dimethoxyethane (2.5 L) was cooled to 0 °C and a solution of potassium tert-butoxide (145 g, 1.29 mol) in tert-butanol (1.3 L) added dropwise. The mixture was then allowed to warm to room temperature and stirred for 3 h before dilution with diethylether (3 L), washing with sat'd sodium bicarbonate (2 x 1.5 L) and drying over magnesium sulfate. Removal of the solvent in vacuo gave tetrahydro-thiopyran-4-carbonitrile as a pale brown oil (88.3 g, 646 mmol).
	With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane; <i>tert</i>-butyl alcohol at 0 - 20℃; for 3h;	1.13 A mixture of compound dihydro-2H-thiopyran-4(3H)-one (0.75 g, 6.46 mmol) and TosMIC (0.138 g, 7.11 mmol) in DME (25 mL) was cooled to 0° C. and a solution of potassium tert-butoxide (0.145 g, 12.9 mmol) in tert-butanol (13 mL) added dropwise. The mixture was then allowed to warm to room temperature and stirred for 3 h before dilution with DCM, washing with Sat. sodium bicarbonate and dried over Na2SO4. Removal of the solvent in vacuo to afford the compound tetrahydro-2H-thiopyran-4-carbonitrile (1 g, crude) as pale brown oil. (0456) 1H-NMR (CDCl3/400 MHz): δ 7.98-7.94 (m, 1H), 7.44-7.43 (d, J=1.6 Hz, 1H), 7.37-7.34 (m, 1H).
	With ethanol; potassium <i>tert</i>-butylate In 1,2-dimethoxyethane at 0℃; for 12h;
1.1 g	With potassium <i>tert</i>-butylate In tetrahydrofuran; 1,2-dimethoxyethane; <i>tert</i>-butyl alcohol at 20℃; for 3h; Inert atmosphere; Cooling with ice;	69.69.1 69.1 Tetrahydrothiopyran-4-carbonitrile 69.1 Tetrahydrothiopyran-4-carbonitrile A 150 mL single-necked flask was charged with potassium tert-butoxide (3.33 g), and anhydrous tetrahydrofuran (20 mL) and tert-butanol (10 mL) were added at the same time. Under nitrogen protection, a solution of tetrahydrothiopyran-4-one (1.5 g) and p-toluenesulfonylmethyl isocyanide (3.0 g) in ethylene glycol dimethyl ether (30 mL) were added dropwise under a condition of an ice bath. After the completion of the addition, the mixture was reacted at room temperature for 3 h. A sample was taken, and the spots of the raw materials disappeared and the reaction was complete as monitored by TLC. Methyl tert-butyl ether (200 mL) was added to the reaction system. The resulting mixture was washed twice with saturated sodium bicarbonate solution (50 mL * 2), dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography, so as to obtain 1.1 g of tetrahydrothiopyran-4-carbonitrile.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP2261213, 2010, A1 Location in patent: Page/Page column 49
[2]Current Patent Assignee: THE UNIVERSITY OF TEXAS SYSTEM - US2019/308978, 2019, A1 Location in patent: Paragraph 0751; 0752
[3]Current Patent Assignee: MERCK & CO INC - WO2003/101993, 2003, A1 Location in patent: Page 38
[4]Straessler, Christoph; Linden, Anthony; Heimgartner, Heinz [Helvetica Chimica Acta, 1997, vol. 80, # 5, p. 1528 - 1551]
[5]Current Patent Assignee: SYNTA PHARMACEUTICALS CORP. - US2006/178532, 2006, A1 Location in patent: Page/Page column 4; 11
[6]Iwabuchi, Yoshiharu; Nagasawa, Shota; Sasaki, Ryota; Sasano, Yusuke; Yamaichi, Aoto [Chemical and Pharmaceutical Bulletin, 2021, vol. 69, # 5, p. 488 - 497]
[7]Current Patent Assignee: ROCHE HOLDING AG - US2006/4045, 2006, A1 Location in patent: Page/Page column 27-28
[8]Current Patent Assignee: MERCK & CO INC - WO2007/23143, 2007, A1 Location in patent: Page/Page column 14
[9]Current Patent Assignee: SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem); Sumitomo Pharma (in: Sumitomo Chemical) - US9416132, 2016, B2 Location in patent: Page/Page column 131; 132
[10]Current Patent Assignee: SHANGHAI FOSUN PHARMACEUTICAL (GROUP) CO., LTD. - WO2018/127130, 2018, A1 Location in patent: Paragraph 257; 258
[11]Current Patent Assignee: NANJING GEAR PHARMA TECH; SINO BIOPHARMACEUTICAL LIMITED - EP3689860, 2020, A1 Location in patent: Paragraph 0595; 0596

25
[ 36635-61-7 ]
[ 1571-08-0 ]
[ 179057-14-8 ]

Yield	Reaction Conditions	Operation in experiment
82%	With potassium carbonate In methanol for 3.5h; Heating;
81%	With potassium carbonate at 80℃; for 1.5h;	General procedure forthe formation of oxazole as illustrated by the synthesis of 5-(4-methoxyphenyl)oxazole (1) General procedure: To a solution of p-anisaldehyde (1.22 mL, 10.0 mmol) in MeOH (25 mL) were added K2CO3 (1.52 g, 11.0 mmol) and TosMIC (1.08 g, 5.50mmol). The reaction mixture was stirred for 1.5 h at 80° C, cooled down to rt, quenched with H2O, and diluted with EtOAc. After removal of the organic layer, the aqueous layer was extracted with EtOAc. The organic layer was combined, dried over Na2SO4, filtered, and concentrated in vacuo. Flash chromatography (3:1 hexanes/EtOAc) afforded 5-(4-methoxyphenyl)oxazole (1) (955 mg, 99%) as a pale yellow solid
65%	With potassium carbonate In methanol for 3h; Inert atmosphere; Reflux;

	With sodium carbonate In methanol for 2h; Heating / reflux;	101 4-Oxazol-5-yl-benzoic acid methyl ester; 4-Formyl-benzoic acid methyl ester (2 g, 11.2 mmol), toluenesulphonylmethyl isocyanide (TOSMIC, 2 g, 10.2 mmol) and anhydrous sodium carbonate (2 g, 18.8 mmol) were brought up in 50 ml_ of anhydrous methanol. The mixture was refluxed for 2 hours, allowed to cool to room temperature, then concentrated in-vacuo. The resulting residue was partitioned between EtOAc and saturated aqueous ammonium chloride. The organic fraction was washed one additional time with ammonium chloride and then once with brine. After drying over MgSO4,the organic fraction was concentrated under vacuum to dryness affording 1.48 g of 4-oxazol-5-yl-benzoic acid methyl ester as a yellow solid.1HNMR (CDCI3): 8.22 (d, J = 8.1 Hz1 2H), 7.97 (s, 1H), 7.74 (d, J = 6 Hz, 2H), 7.48 (s, 1 H), 3.94 (s, 3H).
	Alkaline conditions; Inert atmosphere;

Reference： [1]Tanaka, Akira; Terasawa, Takeshi; Hagihara, Hiroyuki; Sakuma, Yuri; Ishibe, Noriko; Sawada, Masae; Takasugi, Hisashi; Tanaka, Hirokazu [Journal of Medicinal Chemistry, 1998, vol. 41, # 13, p. 2390 - 2410]
[2]Yamamuro, Daisuke; Uchida, Ryuji; Ohtawa, Masaki; Arima, Shiho; Futamura, Yushi; Katane, Masumi; Homma, Hiroshi; Nagamitsu, Tohru; Osada, Hiroyuki; Tomoda, Hiroshi [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 2, p. 313 - 316]
[3]Cho, Er-Chieh; Liu, Chi-Yuan; Tang, Di-Wei; Lee, Hsueh-Yun [Journal of Enzyme Inhibition and Medicinal Chemistry, 2021, vol. 36, # 1, p. 1387 - 1401]
[4]Current Patent Assignee: ASTRAZENECA PLC - WO2007/103456, 2007, A2 Location in patent: Page/Page column 71-72
[5]Kitahara, Masanori; Umeda, Nobuyoshi; Hirano, Koji; Satoh, Tetsuya; Miura, Masahiro [Journal of the American Chemical Society, 2011, vol. 133, # 7, p. 2160 - 2162]
[6]Odani, Riko; Hirano, Koji; Satoh, Tetsuya; Miura, Masahiro [Journal of Organic Chemistry, 2013, vol. 78, # 21, p. 11045 - 11052]

26
[ 36635-61-7 ]
[ 100-52-7 ]
[ 1006-68-4 ]

Yield	Reaction Conditions	Operation in experiment
77%	With potassium carbonate; at 80℃; for 1.5h;	General procedure: To a solution of p-anisaldehyde (1.22 mL, 10.0 mmol) in MeOH (25 mL) were added K2CO3 (1.52 g, 11.0 mmol) and TosMIC (1.08 g, 5.50mmol). The reaction mixture was stirred for 1.5 h at 80 C, cooled down to rt, quenched with H2O, and diluted with EtOAc. After removal of the organic layer, the aqueous layer was extracted with EtOAc. The organic layer was combined, dried over Na2SO4, filtered, and concentrated in vacuo. Flash chromatography (3:1 hexanes/EtOAc) afforded 5-(4-methoxyphenyl)oxazole (1) (955 mg, 99%) as a pale yellow solid
61%	With potassium carbonate; In methanol; for 2h;Reflux;	To a stirred solution of benzaldehyde (1.06 g, 10mmol) and tosylmethyl isocyanide (2.15 g, 11 mmol) in methanol (60 mL) was added K2CO3 (2.76 g, 20mmol) in portions over 10 min. Then the mixture was heated to reflux for 2 h. The mixture was cooled to room temperature, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to afford 5-phenyloxazoleas a light pink solid (0.88 g, 61% yield).
	With potassium carbonate; In methanol;Reflux;	General procedure: To a solution of 3,4-bis(benzyloxy)benzaldehyde(3.0 g, 9.4 mmol, 1 eq) and p-toluenesulfonylmethylisocyanide (TosMIC) (2.0 g, 10.3 mmol,1.1 eq) in MeOH (47 mL) was added potassium carbonate (2.6 g, 18.9 mmol, 2 eq). Thereaction mixture was heated overnight in refluxing MeOH. The solvent was removed underreduced pressure and the crude product was agitated into water at 0 C. A yellow precipitateappeared and was collected by filtration and dried under vacuum (3.1 g, 91 %).

With potassium carbonate; In methanol; for 4h;Inert atmosphere; Reflux;

General procedure: Potassium carbonate (K2CO3) (0.28 g, 2 mmol) was added into the solution of TosMIC (0.23g, 1.2 mmol) in dry methanol (10 mL). Aromatic aldehyde (1) (1 mmol) was then added and the whole mixture was refluxed for 4 h under inert atmosphere (N2). The mixture was allowed to come to room temperature and was concentrated in vacuo under reduced pressure to make it free from methanol. It was then diluted with dichloromethane (50 mL).The organic mixture was washed with 3 % HCl (20 mL), water (20 mL) and brine (25 mL). Organic layer was dried using anhydrous sodium sulphate and then concentrated in vacuo under reduced pressure. This was then purified by column chromatography using petroleum ether-ethyl acetate (4:1) as eluent to get the product as almost colourless solid (2a, 2b). The compound was further confirmed by the spectroscopic data.

Reference： [1]Zeitschrift fur Naturforschung, B: Chemical Sciences,2017,vol. 72,p. 923 - 926
[2]Tetrahedron Letters,1999,vol. 40,p. 5637 - 5638
[3]Journal of Organic Chemistry,2008,vol. 73,p. 3278 - 3280
[4]Organic Letters,2008,vol. 10,p. 4029 - 4032
[5]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 313 - 316
[6]Synlett,2009,p. 302 - 305
[7]Angewandte Chemie - International Edition,2012,vol. 51,p. 6993 - 6997
[8]Tetrahedron Letters,2015,vol. 56,p. 511 - 513
[9]Journal of Medicinal Chemistry,2021,vol. 64,p. 2205 - 2227
[10]Journal of Organic Chemistry,2007,vol. 72,p. 5828 - 5831
[11]Tetrahedron Letters,2009,vol. 50,p. 3273 - 3276
[12]Angewandte Chemie - International Edition,2010,vol. 49,p. 2202 - 2205
[13]Organic Letters,2010,vol. 12,p. 4038 - 4041
[14]Journal of the American Chemical Society,2011,vol. 133,p. 2160 - 2162
[15]Angewandte Chemie - International Edition,2013,vol. 52,p. 4457 - 4461
Angew. Chem.,2013,vol. 125,p. 4553 - 4557,5
[16]Tetrahedron Letters,2013,vol. 54,p. 3188 - 3193
[17]Journal of Organic Chemistry,2013,vol. 78,p. 11045 - 11052
[18]Chemistry - A European Journal,2014,vol. 20,p. 7241 - 7244
[19]European Journal of Organic Chemistry,2014,vol. 2014,p. 7586 - 7589
[20]Asian Journal of Chemistry,2016,vol. 28,p. 1519 - 1522

27
[ 1608-51-1 ]
[ 36635-61-7 ]
(4-(4-fluorophenyl)-1H-pyrrol-3-yl)(phenyl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium hydride In tetrahydrofuran at 25℃; for 0.25h;

Reference： [1]Dannhardt, Gerd; Kiefer, Werner; Kraemer, Godehard; Maehrlein, Sabine; Nowe, Ulrike; Fiebich, Bernd [European Journal of Medicinal Chemistry, 2000, vol. 35, # 5, p. 499 - 510]

28
[ 486-25-9 ]
[ 36635-61-7 ]
[ 1529-40-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium <i>tert</i>-butylate In ethanol; dichloromethane at 20℃; for 1.5h;

Reference： [1]Robarge; Husbands; Kieltyka; Brodbeck; Thurkauf; Newman [Journal of Medicinal Chemistry, 2001, vol. 44, # 19, p. 3175 - 3186]

29
[ 4541-32-6 ]
[ 36635-61-7 ]
[ 212382-59-7 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2,2-dimethylcyclopentanone; [(p-methylphenyl)sulfonylmethyl]isonitrile With potassium <i>tert</i>-butylate In <i>tert</i>-butyl alcohol Stage #2: With lithium aluminium tetrahydride In tetrahydrofuran Further stages.;

Reference： [1]Lloyd; Schmidt; Rovnyak; Ahmad; Atwal; Bisaha; Doweyko; Stein; Traeger; Mathur; Conder; DiMarco; Harper; Jenkins-West; Levesque; Normandin; Russell; Serafino; Smith; Lodge [Journal of Medicinal Chemistry, 2001, vol. 44, # 23, p. 3764 - 3767]

30
[ 36635-61-7 ]
[ 100446-37-5 ]
[ 259816-92-7 ]

Yield	Reaction Conditions	Operation in experiment
45%	With sodium hydride In diethyl ether; dimethyl sulfoxide at 20℃; for 0.0833333h;

Reference： [1]Costi, Roberta; Artico, Marino; Di Santo, Roberto; De Martino, Gabriella; Massa, Silvio; Deidda, Delia; Lampis, Giorgio; Pompei, Raffaello [Medicinal Chemistry Research, 1999, vol. 9, # 6, p. 408 - 423]

31
[ 28469-92-3 ]
[ 36635-61-7 ]
[ 76304-48-8 ]

Yield	Reaction Conditions	Operation in experiment
48%	With sodium t-butanolate In dimethyl sulfoxide at 100℃; for 18h;

Reference： [1]Smith, Nicholas D.; Huang, Dehua; Cosford, Nicholas D. P. [Organic Letters, 2002, vol. 4, # 20, p. 3537 - 3539]

32
[ 24393-59-7 ]
[ 36635-61-7 ]
4-(2-nitrophenyl)-1H-pyrrole-3-carboxylic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With sodium hydride In diethyl ether; dimethyl sulfoxide at 0℃; for 1.25h;

Reference： [1]Bergman, Jan; Rehn, Stanley [Tetrahedron, 2002, vol. 58, # 45, p. 9179 - 9185]

33
[ 36635-61-7 ]
[ 136507-15-8 ]
[ 198821-78-2 ]

Yield	Reaction Conditions	Operation in experiment
96%	With potassium carbonate In methanol for 18h; Inert atmosphere; Reflux;
86%	With potassium carbonate In methanol for 3h; Reflux;	1.A Part A. 5-(2-Methoxy-4-nitrophenyl)oxazole To a solution of 2-methoxy-4-nitrobenzaldehyde (700 mg, 3.86 mmol) and TosMIC (754 mg, 3.86 mmol) in MeOH (7 mL) was added potassium carbonate (561 mg, 4.06 mmol). The reaction mixture was heated at reflux for 3 h. The reactionmixture was cooled to room temperature and was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (25 mL). The aqueous layer was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with brine (25 mL), dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (30% -* 40% ethyl acetate inhexanes) to afford 5-(2-methoxy-4-nitrophenyl)oxazole (732 mg, 86 % yield) as ayellow solid: ‘HNMR(400 MHz, CDC13)ö 7.98 (s, 1H), 7.93 (d,J= 1.8 Hz, 1H),7.92 (s, 1H), 7.84 (d, J 1.8 Hz, 1H), 7.75 (s, 1H), 4.08 (s, 3H); LC/MS (ESI) m/e221.3 [(M+H), calcd for C,0H9N204 221.1].
86%	With potassium carbonate In methanol for 3h; Reflux;	9.A Part A. 5-(2-Methoxy-4-nitrophenyl)oxazole To a solution of 2-methoxy-4-nitrobenzaldehyde (700 mg, 3.86 mmol) and TosMIC (754 mg, 3.86 mmol) in MeOH (7 mL) was added potassium carbonate (561 mg, 4.06 mmol). The reaction mixture was heated at reflux for 3 h. The reaction mixture was cooled to room temperature and was transferred to a separately funnel containing saturated aqueous NaHC03 solution (25 mL). The aqueous layer was extracted with ethyl acetate (3 >< 50 mL). The combined organic layers were washed with brine (25 mL), dried over MgS04, filtered and concentrated. The residue was purified by column chromatography on silica gel (30%→ 40% ethyl acetate in hexanes) to afford 5-(2-methoxy-4-nitrophenyl)oxazole (732 mg, 86 % yield) as a yellow solid: 1H NMR (400 MHz, CDC13) δ 7.98 (s, 1H), 7.93 (d, J= 1.8 Hz, 1H), 7.92 (s, 1H), 7.84 (d, J= 1.8 Hz, 1H), 7.75 (s, 1H), 4.08 (s, 3H); LC/MS (ESI) m/e 221.3 [(M+H)+, calcd for Ci0H9N2O4 221.1].

86%	With potassium carbonate In methanol for 3h; Reflux;
84%	With potassium carbonate In methanol Heating;
84%	Stage #1: [(p-methylphenyl)sulfonylmethyl]isonitrile; 4-nitro-2-methoxybenzaldehyde With potassium carbonate In methanol for 3h; Heating / reflux; Stage #2: With water In methanol at 59 - 69℃;	1.G PART G; 5-(4-Nitro-2-methoxyphenyl)oxazole To a 5 L three-necked round bottom flask equipped with a condenser and a mechanical stirrer was placed compound IF (146.3 g, 0.8076 mol), tosylmethyl isocyanide (157.7 g, 0.8077 mol), [K2CO3] (116.6 g, 0.8075 mol) and [MEOH] (2.5 L). The mixture was heated to reflux under N2 and stirred for 3 hours. Water (1.25 L) was added drop-wise while maintaining the pot temperature between [59-69 °C.] The resulting slurry was cooled to rt, and then to [5 °C] with an ice-water bath. After stirring for 30 minutes at [5 °C,] the slurry was filtered. The resulting cake was washed with water (3 x 400 mL) and dried in a vacuum oven at [45 °C] for 20 hours to compound 1G (148.5 g, [84%)] as a yellow-reddish solid. 1H NMR [(CDC13)] d 8.02 (s, 1H), 7.97 (d, J = 2 Hz, 1H), 7.95 (d, J = 2 Hz, 1H), 7.86 (s, 1H), 7.78 (s, 1H), 4.11 (s, 3H).
68%	With potassium carbonate In methanol for 1.5h; Heating / reflux;	3 A solution of C2 (456 mg, 2.51 mmole), tosylmethyl isocyanide (490 mg, 2.51 mmole) and K2CO3 (347 mg, 251 mmole) were dissolved in methanol and heated to reflux for 1.5 hours. The product mixture was then concentrated in vacuo, redissolved in CH2Cl2, washed with water and brine, dried over Na2SO4 and again concentrated in vacuo. Purified product C3 was obtained through recrystallization (Et2O/hexanes) to yield 375 mg (68%). The 1H NMR was consistent with that of the desired structure.
57%	With potassium carbonate In methanol at 80℃; for 2h;	Preparation of 5- (2-methoxy-4-nitrophenyl) oxazole To a stirred solution of 2-methody-4-nitrobenzaldehyde (3.00 g, 16.6 mmol) in methanol (20mL) was added 1- (isocyanomethane) sulfonyl-4-methylbenzene (3.80 g, 19.9 mmol) followed by K2CO3 (8.00 g, 58.0 mmol) and the reaction mixture was heated to 80 °C for 2 h. After completion of the reaction, reaction mass was poured into sat NaHCOg solution (20 mL) and extracted into ethyl acetate (3 x 100 mL) . The organic layer was washed with water, brine, dried over anhydrous sodium sulphate and concentrated under vacuum to get a crude which was purified by flash silica gel chromatography (eluted at 30% ethyl acetate in hexane) to get 5- (2-methoxy-4-nitrophenyl) -1, 3-oxazole (2.1 g, 57 %) . LCMS : 221 (M+H) .

Reference： [1]Herr, R. Jason; Fairfax, David J.; Meckler, Harold; Wilson, Jeffrey D. [Organic Process Research and Development, 2002, vol. 6, # 5, p. 677 - 681]
[2]Current Patent Assignee: BIOCON LIMITED; BRISTOL-MYERS SQUIBB CO - WO2015/6100, 2015, A1 Location in patent: Page/Page column 67
[3]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2015/116492, 2015, A1 Location in patent: Page/Page column 49
[4]Hartz, Richard A; Ahuja, Vijay T.; Nara, Susheel J.; Kumar, C.M. Vijaya; Brown, Jeffrey M.; Bristow, Linda J.; Rajamani, Ramkumar; Muckelbauer, Jodi K.; Camac, Daniel; Kiefer, Susan E.; Hunihan, Lisa; Gulianello, Michael; Lewis, Martin; Easton, Amy; Lippy, Jonathan S.; Surti, Neha; Pattipati, Sreenivasulu N.; Dokania, Manoj; Elavazhagan, Saravanan; Dandapani, Kumaran; Hamman, Brian D.; Allen, Jason; Kostich, Walter; Bronson, Joanne J.; Macor, John E.; Dzierba, Carolyn D. [Journal of Medicinal Chemistry, 2021, vol. 64, # 15, p. 11090 - 11128]
[5]Watterson, Scott H.; Liu, Chunjian; Dhar; Gu, Henry H.; Pitts, William J.; Barrish, Joel C.; Fleener, Catherine A.; Rouleau, Katherine; Sherbina; Hollenbaugh, Diane L.; Iwanowicz, Edwin J. [Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 20, p. 2879 - 2882]
[6]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2004/214, 2003, A2 Location in patent: Page 41-42
[7]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - US6344465, 2002, B1 Location in patent: Page column 26
[8]Current Patent Assignee: ENDOGENA THERAPEUTICS - WO2020/140050, 2020, A1 Location in patent: Page/Page column 95

34
[ 36635-61-7 ]
[ 5097-93-8 ]
4-(4-phenyl-1H-pyrrol-3-yl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With sodium t-butanolate In dimethyl sulfoxide at 50℃; for 3h;

Reference： [1]Smith, Nicholas D.; Huang, Dehua; Cosford, Nicholas D. P. [Organic Letters, 2002, vol. 4, # 20, p. 3537 - 3539]

35
[ 36635-61-7 ]
[ 18880-00-7 ]
[ 64321-35-3 ]

Yield	Reaction Conditions	Operation in experiment
61%	Stage #1: [(p-methylphenyl)sulfonylmethyl]isonitrile; 1-(bromomethyl)-4-(1,1-dimethylethyl)benzene With sodium hydride In dimethyl sulfoxide at 20℃; for 3h; Stage #2: With water In dimethyl sulfoxide

Reference： [1]Sadhukhan, Subir K.; Viala, Christine; Gourdon, Andre [Synthesis, 2003, # 10, p. 1521 - 1525]

36
[ 36635-61-7 ]
[ 149805-92-5 ]
[ 1026876-69-6 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: [(p-methylphenyl)sulfonylmethyl]isonitrile With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane at -50℃; Stage #2: 6-(dimethylamino)nicotine-3-carboxaldehyde In 1,2-dimethoxyethane at -50℃;

Reference： [1]Chen, Chen; Wilcoxen, Keith M.; Huang, Charles Q.; Xie, Yun-Feng; McCarthy, James R.; Webb, Thomas R.; Zhu, Yun-Fei; Saunders, John; Liu, Xin-Jun; Chen, Ta-Kung; Bozigian, Haig; Grigoriadis, Dimitri E. [Journal of Medicinal Chemistry, 2004, vol. 47, # 19, p. 4787 - 4798]

37
[ 36635-61-7 ]
[ 78712-62-6 ]
[ 738606-39-8 ]
7-isocyano-2,2,13,13-tetramethyl-14-(tetrahydro-pyran-2-yloxy)-7-(toluene-4-sulfonyl)-tetradecanoic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetra-(n-butyl)ammonium iodide; sodium hydride In dimethyl sulfoxide at 20℃; for 20h;

Reference： [1]Mueller, Ralf; Yang, Jing; Duan, Caiming; Pop, Emil; Geoffroy, Otto J.; Zhang, Lian Hao; Huang, Tian-Bao; Denisenko, Sergey; McCosar, Bruce H.; Oniciu, Daniela C.; Bisgaier, Charles L.; Pape, Michael E.; Freiman, Catherine Delaney; Goetz, Brian; Cramer, Clay T.; Hopson, Krista L.; Dasseux, Jean-Louis H. [Journal of Medicinal Chemistry, 2004, vol. 47, # 24, p. 6082 - 6099]

38
[ 36635-61-7 ]
[ 78712-62-6 ]
[ 738606-47-8 ]

Yield	Reaction Conditions	Operation in experiment
67%	With tetra-(n-butyl)ammonium iodide; potassium carbonate In N,N-dimethyl-formamide at 20℃; for 96h;
67%	With tetra-(n-butyl)ammonium iodide; potassium carbonate In DMF (N,N-dimethyl-formamide) for 96h;	{7-Ethoxy-6, 6-dimethyl-1-[(4-methylphenyl) sulfonyll-7-oxoheptyl} (methylidyne) ammonium (108a).; To a mixture of K2CO3 (13.18 g, 95.6 mmol) and Bu4NI (2. 35 g, 6.36 mmol) in dry DMF (50 mL) was added a solution of 103a (24.00 g, 95.6 mmol) and TosMIC (12.41 g, 63.7 mmol) in dry DMF (50 mL) in 20 min under a N2 atmosphere while stirring vigorously. After 4 d, Hz0 (100 mL) was added dropwise while keeping the temperature below 25 °C by cooling with an ice-bath. The resulting mixture was extracted with Et20 (3 x 200 mL). The combined organic layers were washed with saturated aqueous NaHC03 (2 x 200 mL) and dried. The remaining residue was purified by column chromatography (silica; heptane: EtOAc = 6: 1; a layer of NaHC03 was put on the base of the column) to give 108a (15.68 g, 42.8 mmol, 67%) as a slightly yellow oil which slowly solidified on standing. An analytical sample was obtained after recrystallization (0.43 g) from O/heptane at-4 °C to give 108a (0.30 g) as a white solid. mp = 38-39 °C.'H NMR: 8 7.84 (d, J= 8.4 Hz, 2H), 7.40 (d, J= 7. 8 Hz, 2H), 4.43 (dd, J= 3.3, 10.8 Hz, 1H), 4.10 (q, J= 7. 1 Hz, 2H), 2.48 (s, 3H), 2.23-2. 12 (m, 1H), 1.90- 1.77 (m, 1H), 1.66-40 (m, 4H), 1.38-1. 22 (m, 2H), 1.24 (t, J= 7.1 Hz, 3H), 1.15 (s, 6H). 13C NMR : 5 177. 3,164. 6,146. 3,131. 0,129. 93 (2x), 129.87 (2x), 72.8, 60.4, 42.2, 40.2, 28.4, 26.0, 25. 35, 25.30, 24.2, 22.0, 14.5.
12%	With tetra-(n-butyl)ammonium iodide; sodium hydride In dimethyl sulfoxide at 20℃; for 20h;

12%

With NaH; tetra-(n-butyl)ammonium iodide In dimethyl sulfoxide; mineral oil

5 5.6. 7-Isocyano-2,2-dimethyl-7-(toluene-4-sulfonyl)-heptanoic acid ethyl ester (220). Under nitrogen atmosphere, to a stirred solution of tetrabutylammonium iodide (4.23 g, 11.5 mmol) and TosMIC (27.56 g, 141.2 mmol) in anhydrous DMSO (500 mL) was added NaH (60% w/w in mineral oil, 5.80 g, 145.0 mmol), while keeping the internal temperature between 10 and 15° C. After the dropwise addition of 205c (36.60 g, 145.7 mmol), the mixture was stirred at room temperature for 20 h, then cooled with an ice-bath and carefully hydrolyzed with water (600 mL). The solution was extracted with CH2Cl2 (4*150 mL). The combined organic layers were washed with water (200 mL) and half-saturated aqueous NaCl solution (200 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude product mixture (40.9 g) as an orange oil. A portion of this crude product (13.0 g) was purified by column chromatography (silica gel; hexanes/ethyl acetate=10/1, then 9/1), affording 220 (1.92 g, 12%) as a pale yellow oil, 208c (0.70 g, 3%) as a colorless oil, and a mixture of both (2.50 g, ratio 9/1). 1H NMR (CDCl3): δ 7.86 (d, 2H, J=8.1), 7.43 (d, 2H, J=8.1), 4.48 (dd, 1H, J=7.2, 3.6), 4.11 (q, 2H, J=7.2), 2.49 (s, 3H), 2.21-2.16 (m, 1H), 1.90-1.78 (m, 1H), 1.56-1.50 (m, 4H), 1.35-1.20 (m, 2H), 1.25 (t, 3H, J=7.2), 1.16 (s, 6H). 13C NMR (CDCl3): δ 177.8, 165.0, 146.7, 131.3, 130.3, 130.2, 72.9, 60.5, 42.2, 40.2, 28.3, 25.8, 25.3, 25.2, 24.2, 21.9, 14.4. HRMS (LSIMS, nba): Calcd for C19H28NO4S (MH+): 366.1739, found: 366.1746.

Reference： [1]Bell, Roel P.L.; Verdijk, Dennis; Relou, Mike; Smith, Dennis; Regeling, Henk; Ebbers, Eelco J.; C. Leemhuis, Frank M.; Oniciu, Daniela C.; Cramer, Clay T.; Goetz, Brian; Pape, Michael E.; Krause, Brian R.; Dasseux, Jean-Louis [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 1, p. 223 - 236]
[2]Current Patent Assignee: ESPERION THERAPEUTICS, INC. - WO2005/68412, 2005, A1 Location in patent: Page/Page column 226; 231
[3]Mueller, Ralf; Yang, Jing; Duan, Caiming; Pop, Emil; Geoffroy, Otto J.; Zhang, Lian Hao; Huang, Tian-Bao; Denisenko, Sergey; McCosar, Bruce H.; Oniciu, Daniela C.; Bisgaier, Charles L.; Pape, Michael E.; Freiman, Catherine Delaney; Goetz, Brian; Cramer, Clay T.; Hopson, Krista L.; Dasseux, Jean-Louis H. [Journal of Medicinal Chemistry, 2004, vol. 47, # 24, p. 6082 - 6099]
[4]Current Patent Assignee: ESPERION THERAPEUTICS, INC. - US2004/198814, 2004, A1

39
[ 36635-61-7 ]
[ 78712-62-6 ]
[ 413626-91-2 ]

Yield	Reaction Conditions	Operation in experiment
	With tetra-(n-butyl)ammonium iodide; sodium hydride In dimethyl sulfoxide at 20℃; for 23h;
	With tetra-(n-butyl)ammonium iodide; sodium hydride In dimethyl sulfoxide at 0 - 20℃; for 23h;	Representative Procedure for the Synthesis of Ketodiesters: 2,2, 12,12- Tetramethyl-7-oxotridecanedioic acid diethyl ester (209c).; Under N2-atmosphere, to a solution of 205c (22.4 g, 89. 2 mmol) in anhydrous DMSO (300 mL) was added TosMIC (8. 71 g, 44.6 mmol), NaH (60 % w/w in mineral oil, 4.28 g, 107.0 mmol), and tetrabutylammonium iodide (3.30 g, 8.9 mmol) under cooling with an ice-bath. After the addition, the reaction mixture was stirred for 23 h at room temperature, then cooled with an ice-bath, and carefully hydrolyzed with water (300 mL). The solution was extracted with CH2Clz (3 x 150 mL). The combined organic layers were washed with water (100 mL) and half-saturated aqueous NaCI solution (100 mL), dried over anhydrous MgS04, concentrated in vacuo, and dried in high vacuo to give the crude intermediate 208c (26.2 g) as an oil [IH NMR (CDC13) : 8 7.85 (d, 2 H, J= 8.3), 7.42 (d, 2 H, J= 8.3), 4.12 (q, 4 H, J= 7.0), 2.49 (s, 3 H), 1.94 (m, 4 H), 1.60-1. 34 (m, 8 H), 1.30-1. 15 (m, 4 H), 1.25 (t, 6 H, J= 7. 0), 1. 15 (s, 12 H). 13C NMR (CDC13) : 8 177.77, 164.08, 146.43, 131.20, 130.34, 129.96, 81.78, 60.37, 42.12, 40.27, 33.21, 25.25, 25.19, 24.97, 24.26, 21.86, 14.34]. To a solution of 208c (26.0 g) in CH2CI2 (400 mL) was added concd HCt (100 mL) and the reaction mixture was stirred for 45 min at room temperature. The solution was diluted with water (400 mL) and the layers were separated. The aqueous layer was extracted with CH2C12 (300 mL). The combined organic layers were washed with saturated aqueous NaHC03 solution (100 mL) and saturated aqueous NaCI solution (100 mL). The organic phases were dried over anhydrous MgS04, concentrated in vacuo, and dried in high vacuo. The residue was purified by flash chromatography (silica gel; hexanes/ethyl acetate = 95/5, then 90/10) to give 209c (11. 0 g, 67 %) as an oil.'H NMR (CDC13) : 8 4.03 (q, 4 H, J= 7.1), 2.31 (t, 4 H, J= 7.5), 1.45 (m, 8 H), 1.20-1. 08 (m, 4 H), 1.16 (t, 6 H, J= 7.1), 1.07 (s, 12 H). 13C NMR (CDC13) : 8 211.14, 178.05, 60.34, 42.69, 42.20, 40.52, 25.24, 24.71, 24.30, 14.35. HRMS (LSIMS, nba): Calcd for C21H390s (MH+) : 371.2797, found: 371.2763.

Reference： [1]Mueller, Ralf; Yang, Jing; Duan, Caiming; Pop, Emil; Geoffroy, Otto J.; Zhang, Lian Hao; Huang, Tian-Bao; Denisenko, Sergey; McCosar, Bruce H.; Oniciu, Daniela C.; Bisgaier, Charles L.; Pape, Michael E.; Freiman, Catherine Delaney; Goetz, Brian; Cramer, Clay T.; Hopson, Krista L.; Dasseux, Jean-Louis H. [Journal of Medicinal Chemistry, 2004, vol. 47, # 24, p. 6082 - 6099]
[2]Current Patent Assignee: ESPERION THERAPEUTICS, INC. - WO2005/68412, 2005, A1 Location in patent: Page/Page column 251; 260-261

40
[ 36635-61-7 ]
[ 123469-92-1 ]
[ 738606-44-5 ]

Yield	Reaction Conditions	Operation in experiment
	With tetra-(n-butyl)ammonium iodide; sodium hydride In dimethyl sulfoxide at 20℃; for 20h;

Reference： [1]Mueller, Ralf; Yang, Jing; Duan, Caiming; Pop, Emil; Geoffroy, Otto J.; Zhang, Lian Hao; Huang, Tian-Bao; Denisenko, Sergey; McCosar, Bruce H.; Oniciu, Daniela C.; Bisgaier, Charles L.; Pape, Michael E.; Freiman, Catherine Delaney; Goetz, Brian; Cramer, Clay T.; Hopson, Krista L.; Dasseux, Jean-Louis H. [Journal of Medicinal Chemistry, 2004, vol. 47, # 24, p. 6082 - 6099]

41
[ 36635-61-7 ]
[ 175531-13-2 ]
3-tert-butoxycarbonylpyrimido[1,6-a]benzimidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With sodium hydroxide; tetra-(n-butyl)ammonium iodide In dichloromethane; water at -20℃; for 2h;

Reference： [1]Mendiola, Javier; Baeza, Alejandro; Alvarez-Builla, Julio; Vaquero, Juan J. [Journal of Organic Chemistry, 2004, vol. 69, # 15, p. 4974 - 4983]

42
[ 20515-15-5 ]
[ 36635-61-7 ]
[ 881674-21-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride In tetrahydrofuran; dimethyl sulfoxide
	With potassium <i>tert</i>-butylate	R.91 Methyl 4-isopropyl-1H-pyrrole-3-carboxylate Reference Example 91 Methyl 4-isopropyl-1H-pyrrole-3-carboxylate Using p-toluenesulfonylmethyl isocyanide (7.6 g), methyl (2E)-4-methylpent-2-enoate (5.0 g) and potassium tert-butoxide (5.25 g), a procedure as in Reference Example 39 was performed to give the title compound as a pale-yellow oil (yield 3.5 g, 54%). 1H-NMR (CDCl3)δ: 1.22 (6H, d, J=6.9 Hz), 3.35-3.45 (1H, m), 3.79 (3H, s), 6.55-6.57 (1H, m), 7.36-7.38 (1H, m), 8.30 (1H, br).

Reference： [1]Borzilleri, Robert M.; Cai, Zhen-Wei; Ellis, Christopher; Fargnoli, Joseph; Fura, Aberra; Gerhardt, Tracy; Goyal, Bindu; Hunt, John T.; Mortillo, Steven; Qian, Ligang; Tokarski, John; Vyas, Viral; Wautlet, Barri; Zheng, Xioping; Bhide, Rajeev S. [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 5, p. 1429 - 1433]
[2]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP1803709, 2007, A1

43
[ 36635-61-7 ]
[ 5257-24-9 ]
N-[1-tosyl-2-(3'-methyl-2'-indolyl)]ethenylformamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With potassium carbonate; 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 20℃; for 2h;

Reference： [1]Chakrabarty, Manas; Basak, Ramkrishna; Harigaya, Yoshihiro; Takayanagi, Hiroaki [Tetrahedron, 2005, vol. 61, # 7, p. 1793 - 1801]

44
[ 36635-61-7 ]
[ 123469-92-1 ]
[ 738607-02-8 ]

Yield	Reaction Conditions	Operation in experiment
61%	With tetra-(n-butyl)ammonium iodide; potassium carbonate In N,N-dimethyl-formamide at 20℃; for 120h;
61%	With tetra-(n-butyl)ammonium iodide; potassium carbonate In DMF (N,N-dimethyl-formamide) for 120h;	{8-Ethoxy-7, 7-dimethyl-1- [ (4-methylphenyl) sulfonyl]-8-oxooctyl} (methylidyne) ammonium (108b). Under a N2 atmosphere, TosMIC (10.01 g, 51.3 mmol) and 103e (20.41 g, 77.0 mmol) were dissolved in dry DMF (100 mL) and Bu4NI (1.89 g, 5.12 mmol) and K2CO3 (10.62 g, 76.8 mmol) were added while stirring vigorously. After 5 d, the reaction mixture was poured in an ice/HiO mixture (500 mL) and extracted with Et20 (1 x 200 mL, 2 x 100 mL). The combined organic layers were washed with brine (2 x 50 mL) and dried. The remaining residue was purified by column chromatography (silica, heptane: EtOAc = 3: 1) to give in order of elution 103e (5.67 g, 90% pure by GC), an impure batch of 108b (0.94 g), and pure 108b (11.83 g, 61%) as a colorless oil.'H NMR: 8 7.86 (d, J= 8. 1 Hz, 2H), 7.43 (d, J= 8.1 Hz, 2H), 4.45 (dd, J= 10.9, 3.5 Hz, 1H), 4.11 (q, J= 7.2 Hz, 2H), 2.49 (s, 3H), 2.22-2. 11 (m, 1H), 1.90-1. 77 (m, 1H), 1.67-1. 57 (m, 1H), 1.53-1. 42 (m, 3H), 1.24 (t, J= 7.2 Hz, 3H), 1.39-1. 20 (m, 4H), 1.15 (s, 6H). 13C NMR: 8 177.8, 164.8, 146.5, 131.1, 130.1 (2x), 130.0 (2x), 72.8, 60.2, 42.0, 40.3, 29.0, 28. 3,25. 12,25. 06 (2x), 24.5, 21.7, 14.2. HRMS calcd for C2oH29NNa04S (MNa+) : 402.1715, found: 402.1736.

Reference： [1]Bell, Roel P.L.; Verdijk, Dennis; Relou, Mike; Smith, Dennis; Regeling, Henk; Ebbers, Eelco J.; C. Leemhuis, Frank M.; Oniciu, Daniela C.; Cramer, Clay T.; Goetz, Brian; Pape, Michael E.; Krause, Brian R.; Dasseux, Jean-Louis [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 1, p. 223 - 236]
[2]Current Patent Assignee: ESPERION THERAPEUTICS, INC. - WO2005/68412, 2005, A1 Location in patent: Page/Page column 226; 231-232

45
[ 924-44-7 ]
[ 38622-91-2 ]
[ 118994-89-1 ]

Yield	Reaction Conditions	Operation in experiment
54%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; toluene; at 0 - 20℃; for 3h;	INTERMEDIATE 171 - PREPARATION OF ethyl oxazole-5-carboxylate; 1 ,8-Diazabicyclo[5.4.0]undec-7-ene (0.574 ml 3.84 mmol) was added simultaneously with ethyl glyoxalate (50% in toluene, 0.659 ml 3.33 mmol) to a mixture of tosylmethyl isocyanide (0.500 g; 2.560 mmol) in dichloromethane (10 ml.) at 00C. The resulting mixture was stirred at room temperature for 3 hours, diluted in dichloromethane and washed with sodium hydrogen sulphate, sodium carbonate, dried over magnesium sulphate and concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica (eluent 5 to 60 % ethyl acetate in heptane) to yield 0.194 g (54 %) of ethyl oxazole-5-carboxylate as a colorless oil.ESI/APCI(+): 142(M+H).
51%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; toluene; at 0 - 20℃; for 8h;	To a stirred solution of TosMIC (50.0?g, 256?mmol) in CH2Cl2 (255?mL) was added ethyl glyoxylate (~50% in toluene, 56?mL, 283?mmol, 1.1 equiv). The solution was cooled to 0?C, and at this temperature, DBU (38?mL, 254?mmol) was added dropwise. The reaction mixture was allowed to warm to ambient temperature and stirred for 8?h. The reaction mixture was washed with water (~300?mL), organic layers was dried over Na2SO4 and evaporated. The residue was distilled at reduced pressure. bp?=?98?C (25?mbar). M?=?18.3?g. Yield?=?51%. 1H NMR: (CDCl3, 400?MHz) delta?=?1.35 (t, J?=?7.2?Hz, 3?H), 4.35 (q, J?=?7.1?Hz, 2?H), 7.73 (s, 1?H), 7.99 (s, 1?H). 13C NMR (CDCl3, 100?MHz): delta?=?14.2, 61.7, 133.3, 142.9, 153.3, 157.6.
	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; toluene; at 0℃; for 1.33333h;Inert atmosphere;	All weights, volumes and equivalents are relative to toluenesulfonylmethyl isocyanide. Toluenesulfonylmethyl isocyanide (TosMIc) (12.31 g, 1 wt, 1 eq) is dissolved in DCM (61.6 ml, 5 vols) at 0 C under N2. In a seperate vessel, ethyl glyoxalate (50 wt% solution in toluene, 20.6 g, 20.0 ml, 1.67 wt) is diluted with DCM (61.6 ml, 5 vols) under N2 and DBU (12.48 g, 12.35 ml, 1.3 eq, 1.01 wt) is added resulting in a purple solution. The second solution is added to the TosMIc solution over 1 hr, maintaining temperature at 0 C, then checked by HPLC for completion after a further 20 mins. The reaction is quenched by slow addition of 2M HCI (10 vols, 123 ml) and the DCM layer separated. The aqueous layer is re-extracted with DCM (5 vols, 61.6 ml), and the combined organics dried over Na2S04, then evaporated on Buchi, 25 C, 100 mbar to remove DCM and toluene. Distilled at 12 mbar, jacket temperature 105 C, vapour temperature 60-80 C to afford ethyl oxazole-5-carboxylate as a colourless oil.

With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; toluene; at 0℃; for 1.33333h;Inert atmosphere;

All weights, volumes and equivalents are relative to toluenesulfonylmethyl isocyanide.Toluenesulfonylmethyl isocyanide (TosMIc) (12.31 g, 1 wt, 1 eq) is dissolved in DCM (61.6 ml, 5 vols) at 0 C. under N2. In a seperate vessel, ethyl glyoxalate (50 wt % solution in toluene, 20.6 g, 20.0 ml, 1.67 wt) is diluted with DCM (61.6 ml, 5 vols) under N2 and DBU (12.48 g, 12.35 ml, 1.3 eq, 1.01 wt) is added resulting in a purple solution. The second solution is added to the TosMIc solution over 1 hr, maintaining temperature at 0 C., then checked by HPLC for completion after a further 20 mins. The reaction is quenched by slow addition of 2M HCl (10 vols, 123 ml) and the DCM layer separated. The aqueous layer is re-extracted with DCM (5 vols, 61.6 ml), and the combined organics dried over Na2SO4, then evaporated on Buchi, 25 C., 100 mbar to remove DCM and toluene. Distilled at 12 mbar, jacket temperature 105 C., vapour temperature 60-80 C. to afford ethyl oxazole-5-carboxylate as a colourless oil.

Reference： [1]Collection of Czechoslovak Chemical Communications,2009,vol. 74,p. 887 - 900
[2]Tetrahedron Letters,2006,vol. 47,p. 549 - 552
[3]Chemistry - A European Journal,2007,vol. 13,p. 5515 - 5538
[4]Organic Letters,2010,vol. 12,p. 5088 - 5091
[5]Patent: WO2010/142801,2010,A1 .Location in patent: Page/Page column 200
[6]European Journal of Medicinal Chemistry,2018,vol. 154,p. 367 - 391
[7]Patent: WO2012/32067,2012,A1 .Location in patent: Page/Page column 60
[8]Patent: US2013/203772,2013,A1 .Location in patent: Paragraph 0324; 0325; 0326

46
[ 15908-50-6 ]
[ 36635-61-7 ]
3-acetyl-4-(methylthio)-5-(toluene-4-sulfonyl)-pyrrole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 120℃;

Reference： [1]Misra; Panda; Ila; Junjappa [Journal of Organic Chemistry, 2007, vol. 72, # 4, p. 1246 - 1251]

47
[ 36635-61-7 ]
[ 100-39-0 ]
[ 764-42-1 ]
[ 927203-48-3 ]

Yield	Reaction Conditions	Operation in experiment
79%	Stage #1: [(p-methylphenyl)sulfonylmethyl]isonitrile; 1,2-Dicyanoethylene With sodium hydride In N,N-dimethyl-formamide at 0℃; for 2h; Stage #2: benzyl bromide In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 10h;

Reference： [1]Yanagimoto, Takahiro; Toyota, Takeshi; Matsuki, Norio; Makino, Yumi; Uchiyama, Seiichi; Ohwada, Tomohiko [Journal of the American Chemical Society, 2007, vol. 129, # 4, p. 736 - 737]

48
[ 36635-61-7 ]
[ 99134-25-5 ]
[ 938164-56-8 ]

Yield	Reaction Conditions	Operation in experiment
66%	With sodium hydride In diethyl ether; N,N-dimethyl-formamide for 3h;

Reference： [1]Hulcoop, David G.; Lautens, Mark [Organic Letters, 2007, vol. 9, # 9, p. 1761 - 1764]

49
[ 36635-61-7 ]
[ 123415-45-2 ]
[ 737581-58-7 ]

Yield	Reaction Conditions	Operation in experiment
25%	With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane; dichloromethane at -62 - 40℃;

Reference： [1]Thompson, Barry C.; Kim, Young-Gi; McCarley, Tracy D.; Reynolds, John R. [Journal of the American Chemical Society, 2006, vol. 128, # 39, p. 12714 - 12725]

50
[ 36635-61-7 ]
[ 42059-80-3 ]
4-(2-hydroxy-5-nitro-benzoyl)-2-[(4-methylphenyl)sulfonyl]pyrrole [ No CAS ]

Reference： [1]Tetrahedron,2007,vol. 63,p. 7828 - 7832

51
[ 599-67-7 ]
[ 36635-61-7 ]
C₂₃H₂₃NO₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With indium(III) chloride In acetonitrile at 80℃; for 4h;

Reference： [1]Radha Krishna, Palakodety; Raja Sekhar; Lakshmi Prapurna [Tetrahedron Letters, 2007, vol. 48, # 51, p. 9048 - 9050]

52
[ 1378259-70-1 ]
[ 36635-61-7 ]
4-(2-trifluoromethyl-furan-3-yl)-imidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: C₆H₃F₃O₂; [(p-methylphenyl)sulfonylmethyl]isonitrile Stage #2: With ammonia In methanol

Reference： [1]Current Patent Assignee: LIGAND PHARMACEUTICALS INC - US2004/87601, 2004, A1 Location in patent: Page 18

53
[ 36635-61-7 ]
[ 1122-91-4 ]
[ 72571-06-3 ]

Yield	Reaction Conditions	Operation in experiment
87%	With potassium carbonate In methanol for 5h; Reflux;	1.64 4-Bromobenzaldehyde (5.0 g, 27.02 mmol) was reacted with TosMIC (5.80 g, 29.73 mmol) and K2CO3 (4.48 g, 32.4 mmol) in MeOH (80 mL) as per General Procedure 14 to provide 5-(4-bromophenyl)oxazole (5.26 g, 87%) as a white solid.
	With potassium carbonate In methanol for 2h; Heating / reflux;	24.1 Preparation 24-1) A mixture of 4-bromobenzaldehyde (5.00 g), tosylmethyl isocyanide (5.43 g) and potassium carbonate (5.60 g) in methanol (50 ml) was refluxed for 2 hours and concentrated. The residue was taken up between ethyl acetate and saturated aqueous ammonium hydrochloride. The separated organic layer was washed with water and brine, dried over sodium sulfate and filtered. The filtrate was treated with silica gel and the obtained residue was triturated with n-hexane to give 5-(4-bromophenyl)oxazole (4.06 g) as a solid. NMR (CDCl3, δ): 7.37 (1H, s), 7.51-7.58 (4H, m), 7.93 (1H, s) MS (ESI+): 224 (M+H)
	With potassium carbonate In methanol at 70℃; for 2.5h;	A mixture of 4-bromobenzaldehyde (5 g) and tosylmethyl isocyanide (5.3 g) was dried at high vacuum and to it was added methanol (175 mL) to obtain a clear solution. To the reaction mixture was added potassium carbonate (3.7 g) and refluxed under argon at 70 0C for about 2.5 hours. Volatiles were removed under vacuum and the resulting crude residue was purified by column chromatography over silica gel using dichloromethane as eluant to yield the title compound (4.0 g).EIMS (m/z): 225 (M+H)

	In methanol
	In methanol
	In methanol
	Stage #1: [(p-methylphenyl)sulfonylmethyl]isonitrile With C₁₁H₂₀N₃⁽¹⁺⁾*C₈H₁₈NO₄S₂^(1-); 3-butyl-1-methyl-1H-imidazol-3-ium hexafluorophosphate at 40℃; Inert atmosphere; Stage #2: 4-bromo-benzaldehyde at 60 - 70℃; Inert atmosphere; Ionic liquid;

Reference： [1]Current Patent Assignee: CINCERA THERAPEUTICS - WO2021/12018, 2021, A1 Location in patent: Page/Page column 188-189
[2]Yoshizumi, Tomoki; Satoh, Tetsuya; Hirano, Koji; Matsuo, Daisuke; Orita, Akihiro; Otera, Junzo; Miura, Masahiro [Tetrahedron Letters, 2009, vol. 50, # 26, p. 3273 - 3276]
[3]Current Patent Assignee: ASTELLAS PHARMA INC. - EP1140895, 2004, B1 Location in patent: Page 49
[4]Current Patent Assignee: SUN PHARMACEUTICAL INDUSTRIES LIMITED - WO2006/38100, 2006, A1 Location in patent: Page/Page column 80
[5]Yang, Ke; Zhang, Cheng; Wang, Peng; Zhang, Yan; Ge, Haibo [Chemistry - A European Journal, 2014, vol. 20, # 24, p. 7241 - 7244]
[6]Yang, Ke; Wang, Peng; Zhang, Cheng; Kadi, Adnan A.; Fun, Hoong-Kun; Zhang, Yan; Lu, Hongjian [European Journal of Organic Chemistry, 2014, vol. 2014, # 34, p. 7586 - 7589]
[7]Yang, Ke; Chen, Xinyong; Wang, Yuqi; Li, Wanqing; Kadi, Adnan A.; Fun, Hoong-Kun; Sun, Hao; Zhang, Yan; Li, Guigen; Lu, Hongjian [Journal of Organic Chemistry, 2015, vol. 80, # 21, p. 11065 - 11072]
[8]Savanur, Hemantkumar M.; Kalkhambkar, Rajesh G.; Laali, Kenneth K. [European Journal of Organic Chemistry, 2018, vol. 2018, # 38, p. 5285 - 5288]

54
[ 36635-61-7 ]
[ 98272-33-4 ]
[ 649727-30-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride In diethyl ether; dimethyl sulfoxide at 20℃; for 4.25h;	12.e e) [4-CYCLOPROPYL-3-METHOXYCARBONYL-1 H-PYRROLE] A solution of 8.77 g of [P-TOLUENESULPHONYLMETHYL] isocyanide and 5.67 g of methyl 3- cyclopropylacrylate in 72 cm3 of dimethyl sulphoxide and 145 cm3 of diethyl ether is added dropwise over 1.5 hours and under an argon atmosphere to a suspension of 1.73 g (54 [MMOL)] of sodium hydride (at 75% by weight in liquid petroleum jelly) in [90] cm3 of diethyl ether. The reaction is exothermic. After the reaction mixture has been stirred at room temperature for 2.75 hours, 180 cm3 of brine are added cautiously, and the mixture is extracted twice with 100 cm3 of diethyl ether. The organic phase is washed with water, dried and then concentrated to dryness under reduced pressure (2.7 kPa), giving 6.39 g of [4-CYCLOPROPYL-3-METHOXYCARBONYL-1] H-pyrrole in the form of a yellow solid melting at [107°C.] f) Methyl 3-cyclopropylacrylate can be obtained by the method described by [L. BLACKBURN ET AL., CHEM. COMMUN. , 1999,1337-1338.]
	With sodium hydride In diethyl ether; dimethyl sulfoxide at 20℃; for 5h; Inert atmosphere; Schlenk technique;

Reference： [1]Current Patent Assignee: SANOFI - WO2004/7478, 2004, A2 Location in patent: Page 47
[2]Wang, Zheng-Jun; Chen, Xiangyang; Wu, Lei; Wong, Jonathan J.; Liang, Yong; Zhao, Yue; Houk, Kendall N.; Shi, Zhuangzhi [Angewandte Chemie - International Edition, 2021, vol. 60, # 15, p. 8500 - 8504][Angew. Chem., 2021, vol. 133, # 15, p. 8581 - 8585,5]

55
[ 36635-61-7 ]
[ 78712-62-6 ]
[ 738606-47-8 ]
[ 413626-91-2 ]

Yield	Reaction Conditions	Operation in experiment
1: 12% 2: 3%	With tetra-(n-butyl)ammonium iodide; sodium hydride In dimethyl sulfoxide at 10 - 20℃; for 20h;	7-Isocyano-2, 2-dimethyl-7- (toluene-4-sulfonyl)-heptanoic acid ethyl ester (220).; Under nitrogen atmosphere, to a stirred solution of tetrabutylammonium iodide (4.23 g, 11.5 mmol) and TosMIC (27.56 g, 141.2 mmol) in anhydrous DMSO (500 mL) was added NaH (60 % w/w in mineral oil, 5.80 g, 145.0 mmol), while keeping the internal temperature between 10 and 15 °C. After the dropwise addition of 205c (36.60 g, 145.7 mmol), the mixture was stirred at room temperature for 20 h, then cooled with an ice-bath and carefully hydrolyzed with water (600 mL). The solution was extracted with CHxClz (4 x 150 mL). The combined organic layers were washed with water (200 mL) and half- saturated aqueous NaCI solution (200 mL), dried over anhydrous MgS04, and concentrated in vacuo to obtain the crude product mixture (40.9 g) as an orange oil. A portion of this crude product (13.0 g) was purified by column chromatography (silica gel; hexanes/ethyl acetate = 10/1, then 9/1), affording 220 (1.92 g, 12 %) as a pale yellow oil, 208c (0.70 g, 3 %) as a colorless oil, and a mixture of both (2.50 g, ratio 9/1). lH NMR (CDC13) : No. 7.86 (d, 2 H, J= 8.1), 7.43 (d, 2 H, J = 8.1), 4.48 (dd, 1 H, J= 7. 2,3. 6), 4.11 (q, 2 H, J= 7.2), 2.49 (s, 3 H), 2.21-2. 16 (m, 1 H), 1.90-1. 78 (m, I H), 1.56-1. 50 (m, 4 H), 1.35-1. 20 (m, 2 H), 1.25 (t, 3 H, J= 7.2), 1.16 (s, 6 H). 13C NMR (CDCI3) : S 177.8, 165.0, 146.7, 131. 3, 130.3, 130.2, 72.9, 60.5, 42.2, 40.2, 28.3, 25.8, 25.3, 25.2, 24.2, 21.9, 14.4. HRMS (LSIMS, nba): Calcd for ClgH2gNO4S (MHt) : 366.1739, found: 366.1746.

Reference： [1]Current Patent Assignee: ESPERION THERAPEUTICS, INC. - WO2005/68412, 2005, A1 Location in patent: Page/Page column 254; 276-277

56
[ 49678-08-2 ]
[ 36635-61-7 ]
[ 774238-49-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In methanol at 20℃; for 1.5h; Heating / reflux;	38 (E)-5-[2-(4-nitrophenyl)vinyl]oxazole Reference Example 38 (E)-5-[2-(4-nitrophenyl)vinyl]oxazole 4-Nitrocinnamaldehyde (590 mg) and p-toluenesulfonylmethyl isocyanide (650 mg) were dissolved in methanol (40 ml), to the solution potassium carbonate (553 mg) was added at room temperature and heated under reflux for 1.5 hours. After evaporation of the solvent, water (300 ml) was added to the mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and then dried over magnesium sulfate. The solvent was evaporated, the thus obtained residue was purified by silica gel column chromatography, and the fraction obtained from the elude of n-hexane:ethyl acetate = 1:1 was concentrated under reduced pressure to obtain the title compound (394 mg) as a crystalline solid. 1H-NMR (400 MHz, CDCl3) δ: 7.07 (1H, d, J=16.4 Hz), 7.15 (1H, d, J=16.4 Hz), 7.20 (1H, s), 7.61 (1H, d, J=8.8 Hz), 7. 91 (1H, s), 8.23 (2H, d, J=8. 8 Hz).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1612204, 2006, A1 Location in patent: Page/Page column 31-32

57
ethyl-(5-bromo-2,2-dimethyl-pentanoate [ No CAS ]
[ 36635-61-7 ]
[ 311-28-4 ]
[ 413626-90-1 ]

Yield	Reaction Conditions	Operation in experiment
93%	In dimethyl sulfoxide; mineral oil	5 2,2,12,12-Tetramethyl-7-oxo-tridecanedioic acid diethyl ester 2,2,12,12-Tetramethyl-7-oxo-tridecanedioic acid diethyl ester Under N2 atmosphere, to a solution of ethyl-(5-bromo-2,2-dimethyl-pentanoate (11.1 g, 44.2 mol) in DMSO (150 ml, dried over 4 Å molecular sieves) was added p-toluenesulphonylmethyl isocyanide (4.31 g, 22.1 mmol), sodium hydride (60 % w/w in mineral oil, 2.12 g, 53.02 mmol), and tetra-n-butyl ammonium iodide at rt. The reaction mixture was stirred for 18 h at rt, then cooled to 0 ° C., carefilly hydrolyzed with water (10 ml), and then diluted with additional water (250 ml). The solution was extracted with diethyl ether (3 150 ml). The combined organic layers were washed with saturated NaCl solution (2100 ml), dried over anhydrous MgSO4, concentrated in vacuo, and dried in high vacuo to give the p-toluenesulphonyl intermediate (11.1 g, 93 %) as an oil. 1H NMR (CDCl3, 300 MHz): δ=7.85 (d, 2 H, J=8.3); 7.43 (d, 2 H, J=8.3); 4.12 (q, 4 H, J=7.0); 2.49 (s. 3 H); 1.94 (m, 4 H); 1.60 -1.34 (m, 8 H); 1.30 -1.15 (m, 4 H); 1.25 (t, 6 H, J=7.0); 1.15 (s. 12 H). 13C NMR (CDCl3, 75 MHz): δ=177.77, 164.08, 146.43, 131.20, 130.34, 129.96, 81.78, 60.37, 42.12, 40.27, 33.21, 25.25, 25.19, 24.97, 24.26, 21.86, 14.34.

Reference： [1]Current Patent Assignee: ESPERION THERAPEUTICS, INC. - US2003/78239, 2003, A1

58
tin(II)chloride dihydrate [ No CAS ]
[ 7745-93-9 ]
[ 36635-61-7 ]
[ 267648-15-7 ]
[ 267648-14-6 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sulfuric acid; potassium carbonate In 1,4-dioxane; methanol; ethanol; dichloromethane; acetic anhydride; acetic acid; ethyl acetate	E.x.a.m.p.l 5-(4-Amino-2-bromophenyl)oxazole Example 257 Part B 5-(4-Amino-2-bromophenyl)oxazole 2-Bromo-4nitrotoluene (6.29 g, 29.1 mmol) was dissolved in a mixture of glacial acetic acid 46 mL, and acetic anhydride 46 mL, and cooled in an ice bath. Concentrated sulfuric acid (6.9 mL) was added dropwise. Chromium trioxide (8.08 g, 80.8 mmol) was added portionwise over 1 h. The reaction mixture was stirred for an additional 15 min then poured onto ice. The precipitate was isolated by filtration and dissolved in 16 mL of 1,4-dioxane. Concentrated hydrochloric acid (3 mL) was added and the solution was refluxed for 2 h. The reaction mixture was diluted with ethyl acetate (150 mL) and washed with water, saturated sodium bicarbonate and brine. The organic layer was dried over magnesium sulfate and evaporated to yield 1.09 g of 2-bromo-4-nitrobenzaldehyde. The aldehyde was dissolved in methanol (50 mL) and potassium carbonate (0.82 g, 5.96 mmol) and tosylmethyl isocyanide (1.16 g, 5.96 mmol) was added. The reaction mixture was refluxed for 3 h, cooled to room temperature and concentrated. The residue was dissolved in methylene chloride (200 mL) and the organic layer was washed with water and brine. The organic layer was dried over magnesium sulfate, filtered and concentrated to yield 1.53 g. (96%) of 5-(4-nitro-2-bromophenyl)oxazole. 5-(4-Nitro-2-bromophenyl)oxazole (500 mg, 1.86 mmol) was dissolved in a mixture of 10 mL of ethanol and 20 ml of ethyl acetate. Tin dichloride dihydrate 1.74 g (7.72 mmol) was added and the reaction mixture heated to 80° C. for 0.5 h. The reaction mixture was poured into 400 mL of ice/water and neutralized with sodium carbonate. The suspension was extracted with ethyl acetate (3*100 mL), and the combined organic layer was washed with brine, separated and dried over magnesium sulfate, filtered and the solvent removed under reduced pressure to yield 463 mg of 5-(4-amino-2-bromophenyl)oxazole. 93% pure by HPLC method A. Mass spectrum M+H+=240.95, 1H 400 MHz NMR (CD3OD): 8.09 (s, 1H), 7.40 (s, 1H), 7.34 (d, 1H J=8.5 Hz), 6.89 (d, 1H, J=8.5 Hz), 6.60 (m, 1H).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US6399773, 2002, B1

59
[ 36635-61-7 ]
[ 179057-14-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In methanol; ethyl acetate	37.1 Synthesis of Ethyl 2-({2-[(5-nitro-(2-pyridyl))amino]ethyl}amino)-4-(4-(1,3-oxazol-5-yl)phenyl)pyrimidine-5-carboxylate Step 1: Methyl 4-formylbenzoate (Aldrich Chemical Co., St. Louis, Mo.) (5.0 g, 30.5 mmol), anhydrous potassium carbonate (4.55 g, 33 mmol) and p-toluenesulfonylmethyl isocyanide (TOSMIC, Aldrich Chemical Co.) (6.83 g, 30.5 mmol) were refluxed in methanol (100 ml) for 3.5 hours. The mixture was then concentrated to dryness in vacuo. The residue was dissolved in ethyl acetate, washed twice with water, dried and concentrated in vacuo to give methyl 4-(1,3-oxazol-5-yl)benzoate as a beige solid (4.95 g). (NMR (300 MHz, CDCl3: 8.10 (d, 2H), 7.98 (s, 1H), 7.75 (d, 2H), 7.48 (s, 1H), 3.94 (s, 3H)).
	With potassium carbonate In methanol; ethyl acetate	37.1 Step 1 Step 1 Methyl 4-formylbenzoate (Aldrich Chemical Co., St Louis, Mo.) (5.0 g, 30.5 mmol), anhydrous potassium carbonate (4.55 g, 33 mmol) and p-toluenesulfonylmethyl isocyanide (TOSMIC, Aldrich Chemical Co.) (6.83 g, 30.5 mmol) were refluxed in methanol (100 ml) for 3.5 hours. The mixture was then concentrated to dryness in vacuo. The residue was dissolved in ethyl acetate, washed twice with water, dried and concentrated in vacuo to give methyl 4-(1,3-oxazol-5-yl)benzoate as a beige solid (4.95 g). (NMR (300 MHz, CDCl3: 8.10 (d, 2H), 7.98 (s, 1H), 7.75 (d, 2H), 7.48 (s, 1H), 3.94 (s, 3H)).

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - US2002/156087, 2002, A1
[2]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - US6417185, 2002, B1

60
[ 36635-61-7 ]
[ 100-19-6 ]
[ 50712-63-5 ]

Yield	Reaction Conditions	Operation in experiment
13.6 g (77%)	In α,α'-dimethoxydiethyl ether; water; <i>tert</i>-butyl alcohol	1 2-(4-nitrophenyl)propionitrile Preparation 1 2-(4-nitrophenyl)propionitrile A -15°C solution of 4-nitroacetophenone (16.5 g, 100 mmol) and tosylmethyl isocyanide (29.3 g, 150 mmol) in methoxyethyl ether (400 mL) was slowly treated with a room temperature solution of the potassium t-butoxide (28 g, 250 mmol) in t-butanol (200 mL). The reaction mixture was stirred at -15 °C for 1 h and then allowed to warm to room temperature over night. Water (100 mL) was added to the mixture and the organic layer was extracted with ether (3X200 mL). The combined organic fraction was washed with water (3X200 mL), brine (100 mL), dried over sodium sulfate, and concentrated in vacuoto give the crude material which was further purified by flash chromatography (SiO2, 30% EtOAc: Hexane) to give 13.6 g (77%) of the title compound. The NMR spectrum was consistent with the proposed title structure. Field Desorption Mass Spectrum:M+= 176.
13.6 g (77%)	In α,α'-dimethoxydiethyl ether; water; <i>tert</i>-butyl alcohol	61 2-(4-nitrophenyl)propionitrile Preparation 61 2-(4-nitrophenyl)propionitrile A -15+ C. solution of 4-nitroacetophenone (16.5 g, 100 mmol) and tosylmethyl isocyanide (29.3 g, 150 mmol) in methoxyethyl ether (400 ml) was slowly treated with a room temperature solution of the potassium t-butoxide (28 g, 250 mmol) in t-butanole (200 ml). The reaction mixture was stirred at -15 ° C. for 1 h and then allowed to warm to room temperature over night. Water (100 ml) was added to the mixture and organic was extracted with ether (3200 ml). The combined organic fraction was washed with water (3200 ml), brine (100 ml), dried over sodium sulfate, and concentrated in vacuo to give the crude material which was further purified by flash chromatography (SiO2, 30% EtOAc: Hexane) to give 13.6 g (77%) of the title compound. NMR was consistent with the proposed title structure. Field Desorption Mass Spectrum: M+=225.

Reference： [1]Current Patent Assignee: ELI LILLY & CO - EP994110, 2000, A1
[2]Current Patent Assignee: ELI LILLY & CO - US6303816, 2001, B1

61
[ 25597-16-4 ]
[ 36635-61-7 ]
[ 120732-04-9 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran	32 Preparation of ethyl-4-(trifluoromethyl)pyrrole-3-carboxylate STR43 EXAMPLE 32 Preparation of ethyl-4-(trifluoromethyl)pyrrole-3-carboxylate STR43 A solution of potassium t-butoxide (8.11 g, 0.075 mol) in tetrahydrofuran at -60° C. is treated dropwise with a mixture of ethyl 4,4,4-trifluorocrotonate (10.5 g, 0.063 mol) and p-tolylsulfonylmethylisocyanide (12.2 g, 0.063 mol) in tetrahydrofuran over a 1 hour period, stirred at -60° C. for 30 minutes, allowed to warm to room temperature and quenched with water. The reaction mixture is extracted with ether and ethyl acetate. The combined extracts are washed with brine, dried (MgSO4) and concentrated in vacuo to give a solid residue. Recrystallization from 1,2-dichloroethane affords the title compound as a tan solid, 7.3 g (56%), mp 163°-164° C.
	In tetrahydrofuran	37 Preparation of ethyl 4-(trifluoromethyl)pyrrole-3-carboxylate STR43 EXAMPLE 37 Preparation of ethyl 4-(trifluoromethyl)pyrrole-3-carboxylate STR43 A solution of potassium t-butoxide (8.11 g, 0.075 mol) in tetrahydrofuran at -60° C. is treated dropwise with a mixture of ethyl 4,4,4-trifluorocrotonate (10.5 g, 0.063 mol) and p-tolylsulfonyl-methylisocyanide (12.2 g, 0.063 mol) in tetrahydrofuran over a 1 hour period, stirred at -60° C. for 30 minutes, allowed to warm to room temperature and quenched with water. The reaction mixture is extracted with ether and ethyl acetate. The combined extracts are washed with brine, dried (MgSO4) and concentrated in vacuo to give a solid residue. Recrystallization from 1,2-dichloroethane affords the title compound as a tan solid, 7.3 g (56%), mp 163° to 164° C.
	In tetrahydrofuran	31 Preparation of ethyl 4-(trifluoromethyl)pyrrole-3-carboxylate STR42 EXAMPLE 31 Preparation of ethyl 4-(trifluoromethyl)pyrrole-3-carboxylate STR42 A solution of potassium t-butoxide (8.11 g, 0.075 mol) in tetrahydrofuran at -60° C. is treated dropwise with a mixture of ethyl 4,4,4-trifluorocrotonate (10.5 g, 0.063 mol) and p-tolylsulfonylmethylisocyanide (12.2 g, 0.063 mol) in tetrahydrofuran over a 1 hour period, stirred at -60° C. for 30 minutes, allowed to warm to room temperature and quenched with water. The reaction mixture is extracted with ether and ethyl acetate. The combined extracts are washed with brine, dried (MgSO4) and concentrated in vacuo to give a solid residue. Recrystallization from 1,2-dichloroethane affords the title compound as a tan solid, 7.3 g (56%), mp 163°-164° C.

Reference： [1]Current Patent Assignee: BASF SE - US5204332, 1993, A
[2]Current Patent Assignee: PFIZER INC - US5371239, 1994, A
[3]Current Patent Assignee: BASF SE - US5162308, 1992, A

62
[ 154464-88-7 ]
[ 36635-61-7 ]
9-hydroxy-3-formyl-spiro[5.5]undecane [ No CAS ]
9-hydroxy-3-cyano-spiro[5.5]undecane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium <i>tert</i>-butylate In tetrahydrofuran; ethanol	50 9-Hydroxy-3-formyl-spiro[5.5]undecane I-bc EXAMPLE 50 9-Hydroxy-3-formyl-spiro[5.5]undecane I-bc Potassium tert-butylate (1.44 g) was added in small portions, at 0° C. under nitrogen atmosphere, to a solution of 1.40 g of tosylmethylisocyanide and 1.00 g of 3-hydroxy-9-oxo-spiro[5.5]undecane (II-a, Prep. 1) dissolved in 7 ml of anhydrous tetrahydrofuran and 0.53 ml of absolute ethanol. After 0.5 hrs at room temperature, the mixture was filtered on an alumina cake. The cake was washed with dichloromethane and the filtrates, dried over anhydrous sodium sulfate, were evaporated under reduced pressure to give 0.52 g of crude 9-hydroxy-3-cyano-spiro[5.5]undecane as a light oil. [TLC: Rf=0.52 (SiO2 plates, diethylether). 1 H-NMR (300 MHz, CDCl3, ppm from TMS): 3.63 (1H, hept), 2.57 (1H, m), 1.90-1.05 (16H, m)].

Reference： [1]Current Patent Assignee: ALFASIGMA GROUP - US5444082, 1995, A

63
[ 36635-61-7 ]
[ 768-03-6 ]
[ 7126-41-2 ]

Yield	Reaction Conditions	Operation in experiment
	In diethyl ether; water; dimethyl sulfoxide;	EXAMPLE 53 3-Benzoylpyrrole* To a stirred suspension of sodium hydride (8.0 g) in 200 ml of dry ethyl ether was added dropwise a solution of phenylvinylketone (13.22 g) and tosylmethyl isocyanide (19.52) in 150 ml of dry methyl sulfoxide and 300 ml of dry ethyl ether at such a rate that the ether refluxed gently. After complete addition, the suspension was stirred at room temperature for 30 minutes and subsequently hydrolyzed by dropwise addition of 200 ml of water. The ether layer was separated and the aqueous layer extracted with ethyl acetate. The combined organic layers were washed with water, 0.1N sulfuric acid, and again with water. The organic phase was dried over magnesium sulfate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (silica gel, DCM/ethyl acetate, 5:1). The desired fractions were concentrated and the residual oil was crystallized from DCM/hexane, affording the product as crystals (7.11 g), m.p. 98-99 C. (lit* m.p. 96-97 C.). * J. Rokach, P. Hamel and M. Kakushima, Tetrahedron Lett., 22, 4901-4904 (1981). Analysis: Calculated for C11 H9 NO: 77.17%C, 5.30%H, 8.18%N; Found: 76.86%C, 5.41%H, 8.01%N.

Reference： [1]Patent: US5274116,1993,A

64
[ 1423706-19-7 ]
[ 36635-61-7 ]
[ 911641-38-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In ethanol at 65℃; for 4h;	1 Ethyl 1-(4-bromophenyl)-1,4-dihydropyrrolo[2,3-d]imidazole-5-carboxylate To a solution of 4-bromoaniline (8.6 g, 50 mmol) in MeOH (100 mL) was added ethyl glyoxalate (12 mL, 60 mmol, 50% in toluene) and the resulting mixture heated at reflux for 3.5 h. The mixture was then concentrated in vacuo and the resulting residue reconstituted in anhydrous ethanol (100 mL) and treated with tosylmethyl isocyanide (14.6 g, 75 mmol) and potassium carbonate (13.8 g, 100 mmol). The resulting mixture was heated at 65° C. for 4 h, then cooled to rt and poured to water (500 mL) and the resulting solid collected by filtration. The crude material thus isolated was crystallized from ethyl acetate/hexane to give pure 3-(4-bromophenyl)-3H-imidazole-4-carboxylic acid ethyl ester (4). MS (ES+): m/z 295/297 (1/1) [MH+]. 1H NMR (CDCl3, 400 MHz): δ=1.27 (t, J=7.1 Hz, 3H), 4.22 (q, J=7.1 Hz, 2H), 7.22 (d, J=8.7 Hz, 2H), 7.61 (d, J=8.7 Hz, 2H), 7.65 (d, J=0.9 Hz, 1H) and 7.85 (d, J=0.9 Hz, 1H).

Reference： [1]Current Patent Assignee: ASTELLAS PHARMA INC. - US2006/223799, 2006, A1 Location in patent: Page/Page column 9-10

65
Methyl (E)-2-pentenoate [ No CAS ]
[ 36635-61-7 ]
[ 1260827-11-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium <i>tert</i>-butylate	R.89 Methyl 4-ethyl-1H-pyrrole-3-carboxylate Reference Example 89 Methyl 4-ethyl-1H-pyrrole-3-carboxylate Using p-toluenesulfonylmethyl isocyanide (10.1 g), methyl 2-pentenoate (6.01 g) and potassium tert-butoxide (7.01 g), a procedure as in Reference Example 39 was performed to give the title compound as pale-yellow crystals (yield 5.05 g, 64%). 1H-NMR (CDCl3)δ: 1.21 (3H, t, J=7.5 Hz), 2.73-2.81 (2H, m), 3.80 (3H, s), 6.55-6.56 (1H, m), 7.37-7.39 (1H, m), 8.36 (1H, brs).

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP1803709, 2007, A1

66
[ 13894-63-8 ]
[ 36635-61-7 ]
[ 158957-52-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium <i>tert</i>-butylate	R.90 Methyl 4-propyl-1H-pyrrole-3-carboxylate Reference Example 90 Methyl 4-propyl-1H-pyrrole-3-carboxylate Using p-toluenesulfonylmethyl isocyanide (8.6 g), methyl (2E)-hex-2-enoate (5.67 g) and potassium tert-butoxide (5.9 g), a procedure as in Reference Example 39 was performed to give the title compound as colorless crystals (yield 2.8 g, 38%). 1H-NMR (CDCl3)δ:0.96 (3H, t, J=7.5 Hz), 1.57-1.66 (2H, m), 2.68-2.73 (2H, m), 3.79 (3H, m), 6.53-6.55 (1H, m), 7.36-7.38 (1H, m), 8.40 (1H, br).

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP1803709, 2007, A1

67
[ 4903-09-7 ]
[ 38622-91-2 ]
[ 7569-58-6 ]

Yield	Reaction Conditions	Operation in experiment
83%		To a suspension of t-BuOK (4.8 g, 40 mmol) in THF (30 mL) was added a solution of TosMIC (3.9 g, 20 mmol) in THF (10 mL) at -78° C. The mixture was stirred for 10 minutes, treated with a solution of <strong>[4903-09-7]3-chloro-4-methoxy-benzaldehyde</strong> (1.7 g, 10 mmol) in THF (10 mL) dropwise, and continued to stir for 1.5 hours at -78° C. To the cooled reaction mixture was added methanol (10 mL). The mixture was heated at reflux for 30 minutes. Solvent of the reaction mixture was removed to give a crude product, which was dissolved in water (20 mL). The aqueous phase was extracted with EtOAc (20 mL.x.3). The combined organic layers were dried and evaporated under reduced pressure to give crude product, which was purified by column chromatography (petroleum ether/ethyl acetate 10:1) to afford 2-(3-chloro-4-methoxyphenyl)acetonitrile (1.5 g, 83percent). 1H NMR (400 MHz, CDCl3) delta 7.33 (d, J=2.4 Hz, 1H), 7.20 (dd, J=2.4, 8.4 Hz, 1H), 6.92 (d, J=8.4 Hz, 1H), 3.91 (s, 3H), 3.68 (s, 2H). 13C NMR (100 MHz, CDCl3) delta 154.8, 129.8, 127.3, 123.0, 122.7, 117.60, 112.4, 56.2, 22.4.
83%		To a suspension of t-BuOK (4.8 g, 40 mmol) in THF (30 mL) was added a solution of TosMIC (3.9 g, 20 mmol) in THF (10 mL) at -78° C. The mixture was stirred for 10 minutes, treated with a solution of <strong>[4903-09-7]3-chloro-4-methoxy-benzaldehyde</strong> (1.7 g, 10 mmol) in THF (10 mL) dropwise, and continued to stir for 1.5 hours at -78° C. To the cooled reaction mixture was added methanol (10 mL). The mixture was heated at reflux for 30 minutes. Solvent of the reaction mixture was removed to give a crude product, which was dissolved in water (20 mL). The aqueous phase was extracted with EtOAc (20 mL*3). The combined organic layers were dried and evaporated under reduced pressure to give crude product, which was purified by column chromatography (petroleum ether/ethyl acetate 10:1) to afford 2-(3-chloro-4-methoxyphenyl)acetonitrile (1.5 g, 83percent). 1H NMR (400 MHz, CDCl3) delta 7.33 (d, J=2.4 Hz, 1H), 7.20 (dd, J=2.4, 8.4 Hz, 1H), 6.92 (d, J=8.4 Hz, 1H), 3.91 (s, 3H), 3.68 (s, 2H). 13C NMR (100 MHz, CDCl3) delta 154.8, 129.8, 127.3, 123.0, 122.7, 117.60, 112.4, 56.2, 22.4.
83%		E. 2-(3-Chloro-4-methoxyphenyl)acetonitrile; To a suspension of t-BuOK (4.8 g, 40 mmol) in THF (30 mL) was added a solution of TosMIC (3.9 g, 20 mmol) in THF (10 mL) at -78 0C and the mixture was stirred for 10 minutes. A solution of <strong>[4903-09-7]3-chloro-4-methoxy-benzaldehyde</strong> (1.7 g, 10 mmol) in THF (10 mL) was added dropwise, and the reaction was stirred at -78 0C for 1.5 hours. To the cooled reaction mixture was added methanol (10 mL) and the mixture was heated at reflux for 30 minutes. The solvent were evaporated to give a crude residue that was dissolved in water (20 mL). The aqueous phase was extracted with ethyl acetate (20 mL x 3). The combined organic layers were dried and evaporated under reduced pressure to give a crude product that was purified by column chromatography (petroleum ether/ethyl acetate 10: 1) to yield 2-(3-chloro-4- methoxyphenyl)acetonitrile (1.5 g, 83percent). 1H NMR (400 MHz, CDCl3) delta 7.33 (d, J= 2.4 Hz, 1 H), 7.20 (dd, J= 2.4, 8.4 Hz, 1 H), 6.92 (d, J= 8.4 Hz, 1 H), 3.91 (s, 3 H), 3.68 (s, 2 H). 13C NMR (100 MHz, CDCl3) delta 154.8, 129.8, 127.3, 123.0, 122.7, 117.60, 112.4, 56.2, 22.4.

Reference： [1]Patent: US2007/244159,2007,A1 .Location in patent: Page/Page column 90
[2]Patent: US2015/231142,2015,A1 .Location in patent: Paragraph 1569
[3]Patent: WO2008/141119,2008,A2 .Location in patent: Page/Page column 75

68
[ 36635-61-7 ]
[ 6346-05-0 ]
[ 1699-39-4 ]

Yield	Reaction Conditions	Operation in experiment
48%	Stage #1: [(p-methylphenyl)sulfonylmethyl]isonitrile; 3-benzyloxy-4-methoxybenzaldehyde With potassium <i>tert</i>-butylate In tetrahydrofuran at -78℃; for 1.75h; Stage #2: With methanol In tetrahydrofuran for 0.5h; Heating / reflux;	11; 13 To a suspension of t-BuOK (20.2 g, 0.165 mol) in THF (250 mL) was added a solution of TosMIC (16.1 g, 82.6 mmol) in THF (100 mL) at -78° C. The mixture was stirred for 15 minutes, treated with a solution of 3-benzyloxy-4-methoxy-benzaldehyde (10.0 g, 51.9 mmol) in THF (50 mL) dropwise, and continued to stir for 1.5 hours at -78° C. To the cooled reaction mixture was added methanol (50 mL). The mixture was heated at reflux for 30 minutes. Solvent was removed to give a crude product, which was dissolved in water (300 mL). The aqueous phase was extracted with EtOAc (100 mL×3). The combined organic layers were dried and evaporated under reduced pressure to give crude product, which was purified by column chromatography (petroleum ether/ethyl acetate 10:1) to afford 2-(3-(benzyloxy)-4-methoxyphenyl)-acetonitrile (5.0 g, 48%). 1H NMR (300 MHz, CDCl3) δ 7.48-7.33 (m, 5H), 6.89-6.86 (m, 3H), 5.17 (s, 2H), 3.90 (s, 3H), 3.66 (s, 2H). 13C NMR (75 MHz, CDCl3) δ 149.6, 148.6, 136.8, 128.8, 128.8, 128.2, 127.5, 127.5, 122.1, 120.9, 118.2, 113.8, 112.2, 71.2, 56.2, 23.3.

Reference： [1]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - US2007/244159, 2007, A1 Location in patent: Page/Page column 89; 90

69
[ 36635-61-7 ]
[ 78712-62-6 ]
[ 738606-53-6 ]

Yield	Reaction Conditions	Operation in experiment
36%	With NaH; tetra-(n-butyl)ammonium iodide In methanol; sulfuric acid; water; dimethyl sulfoxide; mineral oil	5 5.6. Ethyl 14-Hydroxy-2,2,13,13-tetramethyl-7-oxotetradecanoate (222). According to the procedure for the synthesis of 220, 205c (45.6 g, 182 mmol) was reacted with TosMIC (35.2 g, 180 mmol), tetrabutylammonium iodide (4.3 g, 11.6 mmol) and NaH (60% w/w in mineral oil, 7.3 g, 183 mmol) in anhydrous DMSO (500 mL). To this solution was added tetrabutylammonium iodide (4.3 g, 11.6 mmol) and 207g (43.8 g, 143 mmol) in anhydrous DMSO (20 mL), and then NaH (7.4 g, 185 mmol, 60% w/w in mineral oil) at 10° C. The reaction mixture was stirred at room temperature for 20 h, cooled with an ice-bath, and carefully hydrolyzed with ice-water (1000 mL). The product was extracted with CH2Cl2 (5100 mL). The combined organic layers were dried over anhydrous MgSO4 and concentrated in vacuo to obtain the crude intermediate (115 g) as a red oil. This intermediate was dissolved in 48% H2SO4 (147 mL) and methanol (480 mL) and the mixture was stirred for 100 min at room temperature. After dilution with water (1500 mL), the product was extracted with CH2Cl2 (2150 mL, 100 mL, 50 mL). The combined organic layers were washed with saturated aqueous sodium carbonate solution (150 mL) and saturated aqueous NaCl solution (150 mL), dried over MgSO4, filtered through a short column (aluminum oxide; ethyl acetate), and concentrated in vacuo to obtain the crude product (89 g) as a yellow oil. The crude product was subjected to column chromatography (silica gel; hexanes/ethyl acetate=6:1, then 3:1) to give 222 (17.6 g, 36%) as a pale yellow oil. 1H NMR (CDCl3): δ 4.10 (q, 2H, J=6.9), 3.30 (br. s, 2H), 2.39 (t, 4H, J=6.9), 1.98 (br., 1H), 1.56-1.48 (m, 6H), 1.27-1.18 (m, 11H), 1.14 (s, 6H), 0.85 (s, 6H). 13C NMR (CDCl3): δ 211.5, 178.0, 71.9, 60.3, 42.9, 42.7, 42.2, 40.5, 38.6, 35.1, 30.3, 25.2, 24.7, 24.2, 24.0, 23.8, 14.4. HRMS (LSIMS, gly): Calcd for C20H39O4 (MH+): 343.2848, found: 343.2846.

Reference： [1]Current Patent Assignee: ESPERION THERAPEUTICS, INC. - US2004/198814, 2004, A1

70
[ 62940-38-9 ]
[ 36635-61-7 ]
[ 1006055-20-4 ]

Reference： [1]Synthesis,2007,p. 3653 - 3658

71
[ 36635-61-7 ]
[ 118688-53-2 ]
[ 1006055-16-8 ]

Yield	Reaction Conditions	Operation in experiment
60%	With potassium carbonate In methanol at 70℃;

Reference： [1]Kotha, Sambasivarao; Shah, Vrajesh R. [Synthesis, 2007, # 23, p. 3653 - 3658]

72
[ 2417-72-3 ]
[ 36635-61-7 ]
[ 89654-16-0 ]

Yield	Reaction Conditions	Operation in experiment
64%	Stage #1: Methyl 4-(bromomethyl)benzoate; [(p-methylphenyl)sulfonylmethyl]isonitrile With N,N,N-tributyl-1-butanaminium iodide; sodium hydroxide In dichloromethane at 20℃; Inert atmosphere; Stage #2: With hydrogenchloride In dichloromethane; water monomer at 20℃; for 0.5h;
62%	Stage #1: Methyl 4-(bromomethyl)benzoate; [(p-methylphenyl)sulfonylmethyl]isonitrile With sodium hydroxide; N,N,N-tributyl-1-butanaminium iodide In dichloromethane for 4h; Stage #2: With hydrogenchloride In dichloromethane for 0.5h; Further stages.;
58%	With tetrabutylammonium bromide; sodium hydroxide In dichloromethane for 5h;	1 Example 1 A 250 mL round bottom flask was taken, methyl 4-(bromomethyl)benzoate (1.1690 g, 5 mmol), p-toluenesulfonylmethylisocyanide (0.4881 g, 2.5 mmol) and tetrabutylammonium bromide. (0.1612 g, 0.5 mmol) was dissolved in 30 mL of dichloromethane. After stirring until dissolved, 30 mL of a 30% NaOH solution was slowly added dropwise using a constant pressure dropping funnel, and after stirring for 5 hours, HCl was added and the pH was adjusted to 7. The reaction solution was transferred to a sep. funnel and extracted three times with dichloromethane to give an orange-yellow organic phase. The obtained organic phase was concentrated, then 5 mL dichloromethane was added, and 1 mL of HCl solution was added, and after stirring for 1 hour, it was then quenched with saturated sodium hydrogen carbonate solution. The reaction solution was transferred to a sep. funnel and extracted three times with dichloromethane. It was dried to dryness and then subjected to column chromatography (eluent: ethyl acetate: petroleum ether: = 1:5) to give the title compound. Characterized as follows: 1,3-bis(4,4-carboxylic acid methyl ester phenyl)acetone: yield: 58%.

54%	With N,N,N-tributyl-1-butanaminium iodide; sodium hydroxide In dichloromethane; water monomer at 0 - 20℃; for 4h;	1 EXAMPLE 1: DIPHENYLACETONE DERIVATIVE SYNTHESIS To a 250 mL round-bottomed flask, methyl 4-(bromomethyl)benzoate (12.10 g, 52.83 mmol), p-toluenesulfonylmethyl isocyanide (5.00 g, 25.61 mmol), and tetrabutylammonium iodide (473 mg, 1.28 mmol) were combined in 50 mL dichloromethane with magnetic stirring. The mixture was cooled to 0° C. and then a 40% w/w aqueous sodium hydroxide solution (7.16 mL) was added dropwise to the mixture with rapid stirring. The biphasic mixture was then allowed to warm to room temperature and continue to stirring rapidly for 4 hours after which the reaction was complete indicated by consumption of the methyl 4-(bromomethyl)benzoate by TLC (9:1 heptane:ethyl acetate). Next, a separatory funnel was used to separate the two phases. The organic phase was separated and set aside and the aqueous phase was extracted twice with 20 mL portions of dichloromethane. The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. This crude concentrated residue was dissolved in a mixture of 40 mL dichloromethane and 15 mL tetrahydrofuran. With rapid stirring, 15 mL of 6 M hydrochloric acid was added slowly dropwise and the mixture was allowed to stir at room temperature for 30 minutes. Next the reaction mixture was quenched with saturated sodium bicarbonate. A separatory funnel was used to separate the two phases. The organic phase was separated and set aside and the aqueous phase was extracted twice with 20 mL portions of dichloromethane. The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo over 10 g of silica gel. The dried solid was purified via flash column chromatography using ethyl acetate and heptane (1:20) to yield 4.51 g of Compound (8) (54% yield) confirmed by NMR, and the compound stored at or below 0° C. The overall reaction is illustrated in Reaction Scheme 2.
	Stage #1: Methyl 4-(bromomethyl)benzoate; [(p-methylphenyl)sulfonylmethyl]isonitrile With N,N,N-tributyl-1-butanaminium iodide; sodium hydroxide In dichloromethane; water monomer at 20℃; for 3h; Inert atmosphere; Stage #2: With hydrogenchloride In water monomer

Reference： [1]Messore, Antonella; Madia, Valentina Noemi; Pescatori, Luca; Saccoliti, Francesco; Tudino, Valeria; De Leo, Alessandro; Bortolami, Martina; De Vita, Daniela; Scipione, Luigi; Pepi, Federico; Costi, Roberta; Rivara, Silvia; Scalvini, Laura; Mor, Marco; Ferrara, Fabiana Fosca; Pavoni, Emiliano; Roscilli, Giuseppe; Cassinelli, Giuliana; Milazzo, Ferdinando M.; Battistuzzi, Gianfranco; Di Santo, Roberto; Giannini, Giuseppe [Journal of Medicinal Chemistry, 2018, vol. 61, # 23, p. 10834 - 10859]
[2]Potter, Robert G.; Hughes, Thomas S. [Journal of Organic Chemistry, 2008, vol. 73, # 8, p. 2995 - 3004]
[3]Current Patent Assignee: DALIAN UNIVERSITY - CN110015960, 2019, A Location in patent: Paragraph 0018-0020
[4]Current Patent Assignee: DOW INC - US10894848, 2021, B2 Location in patent: Page/Page column 26
[5]Cai, Xuekang; Cheng, Longhuai; Dong, Yalun; Huang, Haojie; Jiang, Chenyang; Kang, Xueying; Sang, Yueqian; Sun, Lu; Wen, Xin; Xi, Zhen; Yi, Long [Journal of the American Chemical Society, 2022, vol. 144, # 9, p. 3957 - 3967]

73
[ 68223-64-3 ]
[ 36635-61-7 ]
4-fluorocyclohexancarbonitrile [ No CAS ]
4-fluorocyclohexancarbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane; <i>tert</i>-butyl alcohol at 20℃; for 3.5h; Title compound not separated from byproducts.;

Reference： [1]Goss, Rebecca J. M.; Lanceron, Simon E.; Wise, Nicola J.; Moss, Steven J. [Organic and Biomolecular Chemistry, 2006, vol. 4, # 22, p. 4071 - 4073]

74
[ 69550-28-3 ]
[ 36635-61-7 ]
((CH₃)3C)3PAuC(OCH₃)NCH₂SO₂C₆H₄CH₃ [ No CAS ]

Reference： [1]Gazzetta Chimica Italiana,1982,vol. 112,p. 539 - 542

75
ammonium hexafluorophosphate [ No CAS ]
[ 52490-94-5 ]
[ 36635-61-7 ]
[ 819800-18-5 ]

Reference： [1]Polyhedron,2004,vol. 23,p. 2695 - 2707

76
[ 38622-91-2 ]
[ 459-57-4 ]
[ 128101-19-9 ]

Yield	Reaction Conditions	Operation in experiment
89%	With potassium carbonate; In methanol; at 100℃; for 2h;Sealed tube;	General procedure: an aldehyde (1 mmol), TosMIC (1 mmol), and K2CO3 (2 mmol) were added and sealed in a microwave reaction vessel. Three milliliters of methanol was added as a solvent and the reaction mixture was left to react for two hours in the microwave at 100 C. The crude mixture was evaporated and subjected to column chromatography (petroleum ether/ethyl acetate) affording the title compounds.
84%	With potassium carbonate; In methanol; at 90℃; for 0.116667h;Inert atmosphere; Microwave irradiation; Sealed tube;	General procedure: Aryl aldehyde (1.21 mmol), TosMIC (1.33 mmol) and K2CO3 (2.41 mmol) were placed in a 10 ml microwave reaction vesselequipped with a magnetic stirrer. An inert atmosphere was then createdby degassing through evacuating and refilling with argon three times,followed by addition of anhydrous MeOH (5 ml). The resulting cappedreaction mixture was then microwave irradiated at a set temperature of90 C and a power of 120 Watts for 7 min. Upon reaction completion(consumption of TosMIC), the solvent was evaporated in vacuo. Thecrude material was purified by flash column chromatography [elutionwith ethyl acetate and hexane ratio (1:4)] to afford 5-aryl-1,3-oxazolederivatives.
	With potassium carbonate; In methanol; for 2h;Heating / reflux;	To 4-fluorobenzaldehyde (1.50 g, 12 mmol) and tosylmethyl isocyanide (2.384, 1 eq.) in 15 mL of MeOH was added K2CO3 (3.34 g, 2 eq.), and the mixture was heated to gentle reflux for 2 h. Cooling, pouring onto crashed ice/NH4Cl, twofold extraction with AcOEt, washing with water and brine, drying over magnesium sulfate, and evaporation of the solvents, followed by flash chromatography (SiO2, hexane/AcOEt=85/15), yielded 1.83 g of the title compound as light yellow crystals.MS (EI): 163.1 [M]+.

Reference： [1]Zeitschrift fur Naturforschung, B: Chemical Sciences,2017,vol. 72,p. 923 - 926
[2]Molecules,2019,vol. 24
[3]Bioorganic and Medicinal Chemistry,2020,vol. 28
[4]Patent: US2008/306116,2008,A1 .Location in patent: Page/Page column 23
[5]Chemistry - A European Journal,2014,vol. 20,p. 7241 - 7244
[6]European Journal of Organic Chemistry,2014,vol. 2014,p. 7586 - 7589

77
[ 2987-06-6 ]
[ 36635-61-7 ]
[ 95233-32-2 ]

Yield	Reaction Conditions	Operation in experiment
69%	With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane; <i>tert</i>-butyl alcohol at 0 - 20℃; for 5.16667h;	214.A To a solution of 4-(benzyloxy)cyclohexanone (2.94 g, 14.39 mmol, prepared according to procures described in Goodman et al., U.S. Patent Application Publication No. 2006/0292073 A1) in 1,2-dimethoxyethane (14.39 mL, Aldrich) was added tosylmethyl isocyanide (5.62 g, 28.8 mmol, Aldrich) in one portion. The resulting mixture was cooled to 0° C. and potassium t-butoxide solution (3.82 mL, 3.82 mmol, 1.0 M in 2-methyl-2-propanol, Aldrich) was added dropwise. The reaction mixture was stirred at 0° C. for 10 min and at room temperature for 5 hrs and then quenched with 1N HCl (45 mL). The aqueous layer was extracted further with EtOAc (3×). The combined organic extracts were washed with brine, dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (0-40% EtOAc/hexanes) to give a cis and trans mixture of 4-(benzyloxy)cyclohexanecarbonitrile (2.14 g, 69%) as a light orange oil. MS (EST) 216 (M+H).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US2009/23702, 2009, A1 Location in patent: Page/Page column 111

78
[ 626-62-0 ]
[ 36635-61-7 ]
[ 1048971-67-0 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: [(p-methylphenyl)sulfonylmethyl]isonitrile With sodium hydride In diethyl ether; dimethyl sulfoxide at 0 - 20℃; for 0.416667h; Stage #2: Cyclohexyl iodide In diethyl ether; dimethyl sulfoxide at 20℃; for 2h;	1.a NaH (0.8 g, 20.0 mmol, 60% dispersion in oil, 2.0 equiv.) was added to a solution of toluenesulphonylmethyl isocyanide (1.95 g, 10.0 mmol, 1.0 equiv.) in DMSO (10 mL) and Et2O (10 mL) over 5 minutes at 0 C and the reaction mixture was stirred while warming to r.t. for 20 minutes. Cyclohexyl iodide (1.55 mL, 12 mmol, 1.2 equiv) was added dropwise over 3 minutes and the resulting mixture was stirred at r.t. for 2 h. The reaction mixture was then diluted with ethyl acetate (250 mL), and the separated organic layer was washed with water (60 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (20% EtOAc/hexane) to give the product as a white solid: 1H NMR (400MHz, CDCl3) ? 7.88 (d, J= 8.3 Hz, 2 H), 7.43 (d, J = 8.3 Hz, 2 H), 4.30 (d, J= 3.5 Hz, 1 H), 2.50 (s, 3 H), 2.42 (m, 1 H), 2.15 (1 H), 1.85-1.71 (m, 4 H), 1.44-1.19 (m, 5 H).

Reference： [1]Current Patent Assignee: AMGEN INC - WO2008/156601, 2008, A1 Location in patent: Page/Page column 68

79
[ 36635-61-7 ]
[ 130333-46-9 ]
[ 1091618-42-6 ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium carbonate In methanol for 22h; Reflux;

Reference： [1]Location in patent: experimental part Chen, Liqiang; Wilson, Daniel J.; Labello, Nicholas P.; Jayaram, Hiremagalur N.; Pankiewicz, Krzysztof W. [Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 20, p. 9340 - 9345]

80
ethyl 4,4,4-trifluorobut-2-enoate [ No CAS ]
[ 36635-61-7 ]
[ 120732-04-9 ]

Yield	Reaction Conditions	Operation in experiment
80%	With potassium <i>tert</i>-butylate In tetrahydrofuran at 0 - 20℃; for 1.16667h;	Synthesis of 4-(trifluoromethyl)-1H-pyrrole derivatives 7a-e (General method) General procedure: A solution of 3,3,3-trifluoropropenederivative 1a- (2.00 mmol) and TOSMIC (6)(0.41 g 2.10 mmol) in anhydrous THF (5 ml) was addedwith vigorous stirring at 0° to a solution of t-BuOK (0.47 g,4.20 mmol) in dry THF (5 ml) at such a rate as to not letthe temperature of the reaction mixture rise above 5°. Themixture was kept at 0-5° for 10 min and stirred foranother 1 h at room temperature. Saturated aqueous NaCl(5 ml) was added, and the resulting mixture was extractedwith EtOAc (3×7 ml). The combined organic extracts werewashed with H2O (10 ml), dried over Na2SO4. The solventwas evaporated to dryness, and the solid residue waspurified by crystallization.Ethyl 4-(trifluoromethyl)-1-pyrrole-3-carboxylate(7a). Yield 0.35 g (80%), mp 161-163° (C2H4Cl2)(mp 163-164°14). 1H NMR spectrum (CDCl3), δ, ppm(J, Hz): 1.36 (3, t, 3J = 7.1, O23); 4.32 (2, q,3J = 7.1, O23); 7.24-7.26 (1, m, CH); 7.49-7.51(1, m, CH); 9.10 (1, br. s, NH). 13C NMR spectrum(CDCl3), δ, ppm (J, Hz): 14.0 (OCH2CH3); 61.2(OCH2CH3); 114.5 (q, 2JCF = 37.1, C-4); 115.5 (q, 3JCF = 1.8,C-3); 120.8 (q, JCF = 6.3, C-5); 122.9 (q, JCF = 266.0, CF3);126.3 (C-2). 19F NMR spectrum (CDCl3), δ, ppm: -58.2(3F, s, CF3). Mass spectrum (LC/MS), m/z: 206 [M-H]-.Found, %: C 46.49; H 3.86; N 6.80. C8H8F3NO2.Calculated, %: C 46.38; H 3.89; N 6.76
	With sodium hydride In dimethyl sulfoxide

Reference： [1]Markitanov, Yuriy N.; Timoshenko, Vadim M.; Rusanov, Eduard B.; Shermolovich, Yuriy G. [Chemistry of Heterocyclic Compounds, 2021, vol. 57, # 3, p. 253 - 260][Khim. Geterotsikl. Soedin., 2021, vol. 57, # 3, p. 253 - 260,8]
[2]Location in patent: scheme or table Walter, Harald [Zeitschrift fur Naturforschung, B: Chemical Sciences, 2008, vol. 63, # 4, p. 351 - 362]

81
[ 98-03-3 ]
[ 36635-61-7 ]
[ 95-54-5 ]
[ 40353-41-1 ]
[ 70380-70-0 ]

Yield	Reaction Conditions	Operation in experiment
1: 47% 2: 40%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 80℃; for 4h;

Reference： [1]Location in patent: scheme or table Neochoritis, Constantinos; Stephanidou-Stephanatou, Julia; Tsoleridis, Constantinos A. [Synlett, 2009, # 2, p. 302 - 305]

82
[ 36635-61-7 ]
[ 101466-85-7 ]
[ 1093858-33-3 ]

Yield	Reaction Conditions	Operation in experiment
21%	Stage #1: [(p-methylphenyl)sulfonylmethyl]isonitrile With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.0833333h; Stage #2: With trimethyltin(IV)chloride In tetrahydrofuran; hexane at -78℃; Stage #3: ethyl 4-trifluoromethylcinnamate Further stages;

Reference： [1]Sanchez-Garcia, David; Borrell, Jose I.; Nonell, Santi [Organic Letters, 2009, vol. 11, # 1, p. 77 - 79]

83
[ 36635-61-7 ]
[ 75-26-3 ]
[ 58379-84-3 ]

Yield	Reaction Conditions	Operation in experiment
80%	With potassium carbonate; 1-n-butyl-3-methylimidazolim bromide at 20℃; for 24h;

Reference： [1]Location in patent: experimental part Wu, Bo; Wen, Jun; Zhang, Ji; Li, Jing; Xiang, Yong-Zhe; Yu, Xiao-Qi [Synlett, 2009, # 3, p. 500 - 504]

84
[ 36635-61-7 ]
[ 189287-30-7 ]
methyl 4-trifluoromethyl-3-pyrrolecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With sodium hydride In diethyl ether; dimethyl sulfoxide for 0.5h;	14.a In a 50 mL round bottomed flask was added sodium hydride (3.24 mmol, 78 mg) in Et2O (5 mL). A mixture of p-toluenesulfonylmethylisocyanide (3.24 mmol, 634 mg) and (E)-methyl-4,4,4-trifluoromethylbut-2-enoate (3.24 mmol, 500 mg) were added in a 2:1 mixture of Et2O/DMSO (15 mL:7.5 mL). This became slightly warm and was stirred for 30 min. H2O (10 mL) was added and the reaction mixture extracted with Et2O (3×20 mL). The combined Et2O layers were washed with brine, dried over MgSO4, filtered and the solvent removed under reduced pressure to give crude product (590 mg) as a yellow/orange solid. Purification by flash silica chromatography column (eluent 1:4 EtOAc:heptane) gave desired product (154 mg, 0.797 mmol, 25%)1H NMR (400 MHz, MeOD): δ 3.79 (s, 3H), 7.20 (s, 1H), 7.50 (s, 1H).
24.6%	With sodium hydride In diethyl ether; dimethyl sulfoxide for 0.5h;	33.a In a round-bottomed flask was added sodium hydride (3.24 mmol, 78 mg) in Et2O (5 ml_). A mixture of p-toluenesulfonylmethyl isocyanide (3.24 mmol, 634 mg) and (E)-methyl 4,4,4-trifluorobut-2-enoate (3.24 mmol, 500 mg) were added in a 2:1 mixture of Et2O/DMSO (22.5 ml_). The reaction mixture was stirred for a further 30 min then quenched with H2O (1OmL) and extracted with Et2O (x3). The Et2O layers were combined and washed with brine, dried over MgSO4, filtered and the solvent removed to give a yellow/orange solid. Purification by flash chromatography (1 :4 EtOAc:Hept) the desired product (154 mg, 0.80 mmol, 24.6 %). 1H NMR (400 MHz, CD3OD) δ 3.79 (s, 3H) 7.20 (s, 1 H) 7.50 (s, 1 H).

Reference： [1]Current Patent Assignee: ORGANON & CO; MERCK & CO INC - US2009/131455, 2009, A1 Location in patent: Page/Page column 12
[2]Current Patent Assignee: MERCK & CO INC - WO2009/147167, 2009, A1 Location in patent: Page/Page column 49

85
[ 36635-61-7 ]
[ 29421-75-8 ]
[ 1112457-33-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In methanol at 80℃; for 1h;	9 Example 9: 2,6-difluoro-N-(5-(2-methyl-5-(oxazol-5-yl)thiophen-3-yl)pyrazin-2- yl)benzamide (D)To a solution of 4-bromo-5-methylthiophene-2-carbaldehyde (A, 10.5 mmol) and p- tosylmethyl isocyanide (11 mmol) in methanol (80 mL) was added potassium carbonate (13 mmol) and the mixture was heated to 8O0C for 1 h. The solvent was removed in vacuo and diluted in DCM (100 mL) and water (100 mL). The organic layer dried, concentrated and purified by flash chromatography to give 5-(4-bromo-5-methylthiophen-2-yl)oxazole (B, 1.83 g) as yellowish solids. The above solids (80 mg) and 5-(tributylstannyl)pyrazin-2-amine (97 mg) was dissolved in THF (5 mL), tetrakis(triphenylphosphino)palladium(0) (5 mg) was added and the mixture was heated in microwave reactor at 16O0C for Ih. The solvent was removed and residue was purified by column chromatography to give 5-(2-methyl-5-(oxazol-5-yl)thiophen-3- yl)pyrazin-2 -amine (C, 16 mg) as white solids. This solids was treated with 1 eq. of 2,6- difluorobenzoyl chloride in DCM (5 mL) and pyridine (0.1 mL) at rt for 3h. Removal of solvents and purification of residue by flash chromatography gave 2,6-difluoro-N-(5-(2- methyl-5-(oxazol-5-yl)thiophen-3-yl)pyrazin-2-yl)benzamide (D, 12 mg) as white solids. 1H- NMR (CD3OD) ? 9.5 (br, IH), 8.65 (s, IH), 8.18 (s, IH), 7.70 (s, IH), 7.5 (m, 2H), 7.32 (s, IH), 7.1 (t, 2H, J=8), 2.75 (s, 3H) ppm; ESMS calcd for C19H12F2N4O2S: 398.1; found: 399.1 (M + H+).

Reference： [1]Current Patent Assignee: SYNTA PHARMACEUTICALS CORP. - WO2009/17818, 2009, A1 Location in patent: Page/Page column 54-55

86
[ 1012868-70-0 ]
[ 36635-61-7 ]
potassium 5-(4-fluoro-3-trifluoroboratophenyl)-4-(toluene-4-sulfonyl)-4,5-dihydrooxazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With polystyrene-bound 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 3h;

Reference： [1]Molander, Gary A.; Febo-Ayala, Wilma; Jean-Gerard, Ludivine [Organic Letters, 2009, vol. 11, # 17, p. 3830 - 3833]

87
[ 1025113-78-3 ]
[ 36635-61-7 ]
potassium 5-(2-trifluoroboratothiophen-5-yl)-4-(toluene-4-sulfonyl)-4,5-dihydrooxazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With polystyrene-bound 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 12h;

Reference： [1]Molander, Gary A.; Febo-Ayala, Wilma; Jean-Gerard, Ludivine [Organic Letters, 2009, vol. 11, # 17, p. 3830 - 3833]

88
[ 36635-61-7 ]
[ 399-25-7 ]
[ 541-41-3 ]
[ 1173094-27-3 ]
[ 1173094-30-8 ]

Reference： [1]Synthesis,2009,p. 1485 - 1493

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	36635-61-7	MDL No. :	MFCD00000005
Formula :	C₉H₉NO₂S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	CFOAUYCPAUGDFF-UHFFFAOYSA-N
M.W :	195.24	Pubchem ID :	161915
Synonyms :

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.22
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	48.82
TPSA :	42.52 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.56 cm/s

[ CAS No. 36635-61-7 ] {[proInfo.proName]}

Quality Control of [ 36635-61-7 ]

Related Doc. of [ 36635-61-7 ]

Product Details of [ 36635-61-7 ]

Calculated chemistry of [ 36635-61-7 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 36635-61-7 ]

Application In Synthesis of [ 36635-61-7 ]

[ 36635-61-7 ] Synthesis Path-Downstream 1~88

Similar Product of
[ 36635-61-7 ]

Related Functional Groups of
[ 36635-61-7 ]

Aryls

Sulfones

Isocyanides

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	1.31
Log Po/w (WLOGP) :	2.73
Log Po/w (MLOGP) :	1.2
Log Po/w (SILICOS-IT) :	0.52
Consensus Log Po/w :	1.15

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-2.09
Solubility :	1.6 mg/ml ; 0.00822 mol/l
Class :	Soluble
Log S (Ali) :	-1.8
Solubility :	3.07 mg/ml ; 0.0157 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-3.21
Solubility :	0.121 mg/ml ; 0.000619 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.21

Signal Word:	Danger	Class:	6.1
Precautionary Statements:	P261-P280-P301+P310-P311	UN#:	2811
Hazard Statements:	H301+H311+H331	Packing Group:	Ⅲ
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling