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Structure of 2734-70-5

Chemical Structure| 2734-70-5

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Product Details of [ 2734-70-5 ]

CAS No. :2734-70-5
Formula : C8H11NO2
M.W : 153.18
SMILES Code : C1=CC=C(C(=C1OC)N)OC
MDL No. :MFCD00053934
Boiling Point : No data available
InChI Key :HQBJSEKQNRSDAZ-UHFFFAOYSA-N
Pubchem ID :95940

Safety of [ 2734-70-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H319
Precautionary Statements:P305+P351+P338

Computational Chemistry of [ 2734-70-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 43.83
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

44.48 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.89
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

0.82
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.29
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

0.87
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

1.09
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.19

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.58
Solubility 4.05 mg/ml ; 0.0264 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.34
Solubility 7.06 mg/ml ; 0.0461 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-2.28
Solubility 0.809 mg/ml ; 0.00528 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.65 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.26

Application In Synthesis of [ 2734-70-5 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 2734-70-5 ]

[ 2734-70-5 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 463-71-8 ]
  • [ 2734-70-5 ]
  • [ 343790-65-8 ]
YieldReaction ConditionsOperation in experiment
92% With sodium hydrogencarbonate; In dichloromethane; water; at 20℃; for 1.16667h;Cooling with ice; To a mixed solution of dichloromethane (500 mL) and water (500 mL) , 2 , 6-dimethoxyaniline (75.8 g, 495 mmol) and sodium hydrogen carbonate (83.1 g, 990 mmol) were added, and thiophosgene (62.6 g, 544 mmol) was added in small portions with stirring under ice cooling. The mixture was stirred for 10 minutes under ice cooling and then stirred at room temperature for 1 hour. An organic layer was separated, and dichloromethane was added to the aqueous layer to extract organic matter. The organic layers were combined, washed with saturated saline, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. Then, n-hexane was added to the obtained solid, and the resulting solid was collected by filtration to obtain the title compound (88.5 g, 454 mmol, 92%) as a white solid. 1H-NMR (400 MHz, CDC13) δ (ppm) : 3.89 (6H, s), 6.54 (2H, d, J = 8.5 Hz), 7.14 (1H, t, J = 8.5 Hz). MS (APCI): m/z 182 [M+H]+.
86% With 2,6-dimethylpyridine; In dichloromethane; at 0℃; for 2h; 2-isothiocyanato-1,3-dimethoxybenzene, Example 1.0. To a solution of <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (500 g, 3.25 mol, 1 eq) in DCM (5.0 L) was added 2,6-lutidine (1.5 L, 13.0 mol, 4 eq). The reaction mixture was cooled to 0 C (internal temperature) and CSC12 (374 mL, 4.88 mol, 1.5 eq) was added drop-wise. The reaction mixture was allowed to stir for 2 h. The solvent was evaporated under reduced pressure and the residue was purified on silica gel to provide the title compound 1.0, 2-isothiocyanato-1,3- dimethoxybenzene as white solid (1.06 g, 2.80 mol, 86%). LCMS (ESI pos. ion) mlz:196 (M+H). ‘H NMR (400 MI-Tz, CDC13) 7.16 (t, J 8.48 Hz, 1H), 6.55 (d, J 8.48 Hz, 2H), 3.90 (s, 6H).
86% With 2,6-dimethylpyridine; In dichloromethane; at 0℃; for 2h; 2-Isothiocyanato-1,3-dimethoxybenzene, Example 10.0 To a solution of <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (500 g, 3.25 mol, 1 eq) in DCM (5.0 L) was added 2,6-Lutidine (1.5 L, 13.0 mol, 4 eq). The reaction mixture was cooled to 0 C. (internal temperature) and CSCl2 (374 mL, 4.88 mol, 1.5 eq) was added drop-wise. The reaction mixture was allowed to stir for 2 h. The solvent was then evaporated under reduced pressure and the material thus obtained was purified by SiO2 column to provide Example 10.0, 2-isothiocyanato-1,3-dimethoxybenzene, as a white solid (1.06 g, 2.80 mol, 86%). LCMS (ESI pos ion) m/z: (M+H)+=196. 1H NMR (400 MHz, CDCl3) δ 7.16 (t, J=8.48 Hz, 1H), 6.55 (d, J=8.48 Hz, 2H), 3.90 (app s, 6H).
86% With 2,6-dimethylpyridine; In dichloromethane; at 0℃; for 2h; To a solution of <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (500 g, 3.25 mol, 1 eq) in DCM (5.0 L) was added 2,6- lutidine (1.5 L, 13.0 mol, 4 eq). The reaction mixture was cooled to 0 C (internal temperature) and CSCl2(374 mL, 4.88 mol, 1.5 eq) was added dropwise. The reaction mixture was then stirred for 2 h. The solvent was evaporated under reduced pressure, and the material thus obtained was purified by silica column to provide the title compound, 2- isothiocyanato-1,3-dimethoxybenzene, Example 465.0 as a white solid (1.06g, 2.80 mol, 86%).1H NMR (400 MHz, CDCl3) δ 7.16 (t, J = 8.48 Hz, 1H), 6.55 (d, J = 8.48 Hz, 2H), 3.90 (m, 6H). LCMS (ESI pos. ion) m/z: (M+H)+196.
86% With 2,6-dimethylpyridine; In dichloromethane; at 0℃; for 2h; To a solution of <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (500 g, 3.25 mol, 1 eq) in DCM (5.0 L) was added 2,6-lutidine (1.5 L, 13.0 mol, 4 eq). The reaction mixture was cooled to 0 C (internal temperature) and CSCl2 (374 mL, 4.88 mol, 1.5 eq) was added drop-wise. The reaction mixture was allowed to stir for 2 h. The solvent was evaporated under reduced pressure and the initial product was purified by SiO2 column to provide the title compound, 2-isothiocyanato-1,3- dimethoxybenzene, Example 1.2 as white solid (1.06g, 2.80 mol, 86%). LCMS (ESI pos. ion) m/z: (M+H)+ = 196. 1H NMR (400 MHz, CDCl3) δ 7.16 (t, J = 8.48 Hz, 1H), 6.55 (d, J = 8.48 Hz, 2H), 3.90 (m, 6H).
86% With 2,6-dimethylpyridine; In dichloromethane; at 0℃; for 2h; To a solution of <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (500 g, 3.25 mol, 1 eq) in DCM (5.0 L) was added 2,6-lutidine (1.5 L, 13.0 mol, 4 eq). The reaction mixture was cooled to 0 C (internal temperature) and CSC12 (374 mL, 4.88 mol, 1.5 eq) was added dropwise. The reaction mixture was then stirred for 2 h. The solvent was evaporated under reduced pressure and the material thus obtained was purified by SiC column to provide the title compound, 2-isothiocyanato-l,3-dimethoxybenzene, Example 82.0 as a white solid (1.06g, 2.80 mol, 86%). LCMS (ESI pos. ion) m/z: (M+H)+ = 196. NMR (400 MHz, CDCI3) δ 7.16 (t, J= 8.48 Hz, 1H), 6.55 (d, J = 8.48 Hz, 2H), 3.90 (m, 6H).
86% With 2,6-dimethylpyridine; In dichloromethane; at 0℃; for 2h;Inert atmosphere; To a solution of <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (500 g, 3.25 mol, 1 eq) in DCM (5.0 L) was added 2,6- lutidine (1.5 L, 13.0 mol, 4 eq). The reaction mixture was cooled to 0 C (internal temperature) and CSC12 (374 mL, 4.88 mol, 1.5 eq) was added dropwise. The reaction mixture was then stirred for 2 h. The solvent was evaporated in vacuo and the initial mass was purified by Si02 column to provide the title compound, Example 372.0, as a white solid (1.06g, 2.80 mol, 86%). LCMS (ESI pos. ion) m/z: (M+1)+ = 196. 1HNMR (400 MHz, CDC13) ö 7.16 (t,J= 8.48 Hz, 1H), 6.55 (d,J= 8.48 Hz, 2H), 3.90 (m, 6H).
53% With sodium hydrogencarbonate; In dichloromethane; water; at 0 - 20℃; for 1.16667h; To a mixture of dichloromethane (50 mL) and water (50 mL) were added 2,6- dimethoxyaniline (4.6 g, 30 mmol, 1 equiv) and sodium bicarbonate (5.0 g, 60 mmol, 2 equiv). Then thiophosgene (2.6 mL, 33 mmol, 1.1 equiv) was added in small portions with stirring at 0C. After addition, the mixture was stirred for 10 mins at 0C and then at room temperature for 1 hour. The organic layer was separated and the aqueous layer was extracted with DCM (2*50 mL). The combined organic extracts were washed with brine (30 mL), dried over anhydrous Na2S04, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (eluted with PE/EtOAc = 200/1) to afford the title compound 2-isothiocyanato-l,3-dimethoxybenzene as an off-white solid (3.1 g, 53% yield). NMR (400 MHz, DMSO-de) d: 7.29 (t, J = 8.0 Hz, 1H), 6.76 (d, J = 8.0 Hz, 2H), 3.86 (s, 6H). LC-MS: m/z 196.1 (M+H)+
With 2,6-dimethylpyridine; In dichloromethane; at 0℃; for 2h; To a solution of <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (500 g, 3.25 mol, 1 eq) in DCM (5.0 L) was added 2,6- lutidine (1.5 L, 13.0 mol, 4 eq). The reaction mixture was cooled to 0 C (internal temperature) and CSC12 (374 mL, 4.88 mol, 1.5 eq) was added drop-wise. The reaction mixture was allowed to stir for 2 h. The solvent was then evaporated in vacuo, and the initial mass was purified by Si02 column to provide 2-isothiocyanato-1,3- dimethoxybenzene, Example 28.0 as white solid. LCMS-ESI (pos.) m/z: (M+H) = 196. 1H NMR (400 MHz, CDC13) ö 7.16 (t, J= 8.48 Hz, 1H), 6.55 (d, J= 8.48 Hz, 2H), 3.90 (app s, 6H).

  • 2
  • [ 6665-97-0 ]
  • [ 2734-70-5 ]
YieldReaction ConditionsOperation in experiment
98% With iron(0); glacial acetic acid; In ethanol; water monomer; at 90℃; To a solution of 78 (170 mg, 0.93 mmol) in AcOH (5 mL), EtOH (5 mL) and H2O (2.5 mL) was added iron powder (311 mg, 325 mesh, 5.57 mmol) portion wise. The mixture was then heated at 90 C. under N2 overnight. After cooling to room temperature, the mixture was poured onto ice, basified using solid Na2CO3 and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to yield 79 as a pale yellow solid (139 mg, 98%). MS (APCD): m/z 154 (100%, [M+H]+) which was used in the next step without further purification.
80% With palladium 10% on activated carbon; hydrogen; In ethanol; at 20 - 30℃; under 7500.75 Torr;Autoclave; In a 150-ml autoclave, 2,6-dimethoxynitrobenzene (10 g, 55 mmol) was added in that order,30ml absolute ethanol,0.2 g of 10% Pd / C catalyst,Into high purity hydrogen to 1.0MPa,Reaction at room temperature.When the hydrogen pressure gauge is not falling as the end of the reaction.Filtration, the filtrate spin dry,A white solid 6.7g, 80% yield.
60% With hydrogenchloride; dichloro-λ2-stannane dihydrate; In diethyl ether; at 20℃; for 30.0h; To conc. hydrochloric acid (15 mL) was added dihydrated tin chloride (69.6 g, 308 mmol) at rt. In another flask, compound 50 (5.6 g, 30.6 mmol) was solubilized in ethyl ether (60 mL). The resulting mixture was added by small portions to dissolved tin chloride in hydrochloric acid. The reaction was run to completion over 12 hours at rt. The mixture was then poured into cold water and basified to pH = 9 with aqueous sodium hydroxide and stirred at rt for 3 hours. The final suspension was filtered on Celite. After dilution of the filtrate with ethyl acetate and washing with water, the organic layer was dried over MgSO4 and concentrated under reduced pressure. The off-white solid obtained 51 (2.81 g, 60%) presented the same physico-chemical properties as the commercial product. TLC Rf (EtOAc) = 0.83; 1H NMR (CDCl3, 400 MHz) δ (ppm) 3.81 (s, 2H, NH2), 3.86 (s, 6H, 2OCH3), 6.53 (d, J = 8.2 Hz, 2H, ArH), 6.69 (t, J = 8.2 Hz, 1H, ArH).
With iron(0); glacial acetic acid; In ethanol; water monomer; at 90℃;Inert atmosphere; 2,6-Dimethoxy-phenylamine (79): To a solution of 78 (170 mg, 0.93 mmol) in AcOH (5 mL), EtOH (5 mL) and H2O (2.5 mL) was added iron powder (311 mg, 325 mesh, 5.57 mmol) portion wise. The mixture was then heated at 90 C. under N2 overnight. After cooling to room temperature, the mixture was poured onto ice, basified using solid Na2CO3 and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to yield 79 as a pale yellow solid (139 mg, 98%). MS (APCI): m/z 154 (100%, [M+H]+) which was used in the next step without further purification.

  • 3
  • [ 2734-70-5 ]
  • [ 108-24-7 ]
  • [ 131157-26-1 ]
YieldReaction ConditionsOperation in experiment
60% In dichloromethane; at 20℃; for 24h;Inert atmosphere; Acetic anhydride (2.97 mL, 31.45 mmol) was added to a solution of aniline 51 (2.19 g, 14.3 mmol) in dry dichloromethane (50 mL) under inert atmosphere. The reaction was stirred at room temperature for 24 hours. Upon completion, the reaction mixture was washed with a saturated solution of sodium carbonate, the organic layer dried over MgSO4 and the solvent removed under reduced pressure. The acetanilide 52 was obtained as a white solid (1.67 g, 60%) after crystallization from Et2O; mp (Et2O) 128-130 C; TLC Rf (EtOAc) = 0.37; 1H NMR (CDCl3, 400 MHz) δ (ppm) 2.20 (large s, 3H, NHCOCH3), 3.84 (s, 6H, 2OCH3), 6.42 (large s, 1H, NHCOCH3), 6.59 (d, J = 8.4 Hz, 2H, ArH), 7.20 (t, J = 8.2 Hz, 1H, ArH). 13C NMR (CDCl3, 100 MHz) δ 23.3 (CH3), 55.9 (2CH3), 104.3 (2CH), 107.4 (C), 127.8 (CH), 155.6 (2C), 172.9 (C). IR ν cm-1: 1104, 1253, 1437, 1474, 1537, 1590, 1651, 3184, 3256. Calcd. for C10H13O3N: C, 61.53; H, 6.71; N, 7.17. Found: C, 61.36; H, 6.94; N, 7.01.
  • 4
  • [ 573-54-6 ]
  • [ 2734-70-5 ]
  • [ 103942-80-9 ]
  • 7
  • [ 2734-70-5 ]
  • [ 598-21-0 ]
  • 2-bromo-<i>N</i>-(2,6-dimethoxy-phenyl)-acetamide [ No CAS ]
  • 8
  • [ 2734-70-5 ]
  • N-(2,6-dimethoxyphenyl)-2-(2-methoxybenzyl)-3-oxoisoindoline-1-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
17% To a solution of 2-(2-methoxybenzyl)-3-oxoisoindoline-l-carboxylic acid (59mg, 0.2 mmol), and NEt3 (84 μL, 0.3 mmol) in DMF (2 mL), N,N,N',N'-tetramethyl- fluoroformamidinium hexafluuorophosphate (79mg, 0.3 mmol) was added, and the mixture was stirred at room temperature for 30min. 2,6-Dimethoxyaniline (46 mg, 0.3 mmol) was added in one portion, and the reaction mixture was heated at 50 0C for 45 min. The mixture was cooled down to room temperature, filtered, and purified by preparative HPLC to yield the title compound (15 mg, 17%).
  • 10
  • [ 263854-44-0 ]
  • [ 2734-70-5 ]
  • [ 263849-96-3 ]
YieldReaction ConditionsOperation in experiment
55% With N-ethyl-N,N-diisopropylamine; HATU; In DMF (N,N-dimethyl-formamide); Thymol (1.0 eq, 33.3mmol) and methyl 5-(chloromethyl)-2-furoate (1.0 eq, 33.3mmol) were dissolved in nitromethane (120mL, 0.2M). Aluminum trichloride (1.0 eq, 33.3mmol) dissolved in 25mL nitromethane was added to the above solution under nitrogen and heated to slow reflux over 10 min. The heat was turned off and left under nitrogen overnight. The reaction was quenched with 100mL of water and exctracted with dichloromethane. The crude mixture was evaporated to dryness and loaded onto plug chromatography column (1g crude/100g silica gel ratio). The column was eluted with 7 and 11% ethyl acetate/hexanes to yield the desired product (2.9 g, 30%). The ester was hydrolyzed to acid by lithium hydroxide in THF/MeOH/H2O (35/25/25). To a solution containing the 5-(4-hydorxy-5-isopropyl-2-methylbenzyl)-2-furoic acid (1.0eq, 3.6 mmol, 0.5M), and <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (1.0eq, 3.6mmol) were dissolved in DMF. To this mixture, HATU (1.0 eq, 3.6 mmol) and di-isopropyl ethyl amine (1.0 eq, 3.6 mmol) were added and stirred overnight. The mixture was heated for 10min at 45C. The solution was placed into ethyl acetate (3x volume) and washed with water. The organic layer was evaporated to syrup and eluted on plug column chromatography (1:100 g crude/g silicagel) with 30 and 50 % ethyl acetate/hexane to yield: N-(2,6-dimethoxyphenyl)-5-(4-hydroxy-5-isopropyl-2-methylbenzyl)-2furamide (820 mgs, 55% yield). 1HNMR (CDCl3) 7.22ppm (1H, t, J=8.68 Hz), 7.08ppm (1H, d, J=3.40 Hz), 6.99ppm (1H,s), 6.64ppm (2H, d, J=8.68 Hz), 6.61ppm (1H, s), 5.97 ppm (1H, d, J=3.40 Hz), 3.95ppm, (2H,s), 3.85ppm, (6H,s), 3.17ppm, (1H,pentet, J=6.8 Hz) 2.23ppm, (3H,s), 1.25 ppm(3H,s), and 1.23ppm (3H, s).
  • 11
  • [ 1466-76-8 ]
  • [ 2734-70-5 ]
YieldReaction ConditionsOperation in experiment
With 4-methyl-morpholine; diphenylphosphoranyl azide; hydrogen; copper(I) iodide; benzyl alcohol;palladium; In methanol; 1,2-dichloro-ethane; Example 16A 2,6-Dimethoxyaniline To a stirred solution of 2,6-dimethoxybenzoic acid (2.00 g, 11.0 mmol) in 1,2-dichloroethane (45 mL) at ambient temperature was successively added N-methylmorpholine (1.45 mL, 13.2 mmol) and diphenylphosphoryl azide (2,60 mL, 12.1 mmol). After heating the mixture for 2 hours at 75 C., cuprous iodide (150 mg) and benzyl alcohol (2.27 mL, 22.0 mmol) were added and heating was continued overnight. Solvents were removed in vacuo and the residue was chromatographed on silica gel, eluding with 4:1 hexane-ethyl acetate to give the intermediate carbamate (1.50 g, 48 % yield) as a white, crystalline solid. The solid was dissolved in methanol (15 mL) and added to a flask purged with nitrogen containing 10% palladium-on-charcoal (500 mg). The mixture was placed under a balloon of hydrogen and stirred 4 hours at ambient temperature. The mixture was filtered through a pad of Celite and solvents were removed in vacuo to give the title compound (800 mg, 48% yield).
  • 12
  • [ 42310-45-2 ]
  • [ 16462-27-4 ]
  • [ 2734-70-5 ]
  • [ 56066-19-4 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; acetic acid; In water; EXAMPLE 11 Preparation of 2,4-Diamino-5-(4-amino-3,5-dimethoxybenzyl)pyrimidine A mixture of 2,4-diamino-5-hydroxymethylpyrimidine (4.30 g, 30.0 mmol), prepared from 2,4-diamino-5-cyanopyrimidine as described in U.K. Pat. No. 1 413 472, <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (5.05 g, 33.0 mmol), acetic acid (60 mL), and concentrated hydrochloric acid (4.2 mL) was refluxed for 41/2 hours, cooled, and filtered to give the hydrochloride salt of the title compound (7.13 g, 76.2%). The salt was dissolved in water and the solution made basic with concentrated ammonium hydroxide. The resulting precipitate was filtered, washed with water, and dried to give the title compound (5.18 g, 62.7%). Calculated for C13 H17 N5 O2: C, 56.72; H, 6.22; N, 25.44. Found: C, 56.63; H, 6.29; N, 25.39.
  • 13
  • [ 2734-70-5 ]
  • [ 23957-21-3 ]
YieldReaction ConditionsOperation in experiment
79% With bromine; In chloroform; at 0 - 21℃; for 14h; This reaction was not performed under inert conditions.A solution of bromine (1.00 mL, 3.12 g, 1.95 mmol, 1.00 equiv) in chloroform (50 mL) was added to asolution of <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (3.06 g, 2.00 mmol, 1.03 equiv) in chloroform (50 mL) at 0C over thecourse of 1 h. Afterwards, the solution was warmed up to 21 C and stirred for additional 14 h. Then,NaOH (2 M) was added to adjust the pH to 11. The water phase was extracted with ethyl acetate (3 ×100 mL). The combined organic phases were washed with water (100 mL), brine (100 mL), dried overMgSO4 and filtered. The crude product was purified by column chromatography (eluent: nhexane/DCM 95:5) to yield S4 as a colorless solid (3.66 g, 1.58 mmol, 79%, Lit.:[14] 77%)
70% With bromine; In dichloromethane; at 4 - 20℃; To a stirred solution of <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (9.0 g, 58.7 mmol, 1.0 eq) in 350 mL of anhydrous DCM was dropwise added over 30 min a Br2solution in 50 mL of anhydrous DCM at 4 C. An additional 200 mL was added to the slurry to achieve a semi-homogeneous solution. The reaction mixture was stirred overnight at room temperature. The dark brown mixture was cooled to 4 C and basified by addition of 1.0 M NaOH solution (ca.100 mL) to pH = 10-11. The mixture was diluted with 200 mL of DCM and the layers are separated. The aqueous layer was extracted with DCM (200 mL total). The combined DCM layers were washed with water, brine, and dried over Na2SO4. After concentration in vacuo, the crude product was obtained as a slightly reddish solid. The residue was dissolved in DCM (8 mL) and loaded onto a 220 g HP silica gel Gold RediSep column and purified via ISCO (gradient elution: 5 - 95% EA in hexanes), pure fractions combined, and the solvent evaporated in vacuo. The solid was triturated with DCM and hexanes and filtered. The off-while solid was dried in vacuo giving the title compound R26 as an off-white230.99; found 231.9 and 234.0 (M+H).1H NMR (500 MHz; CDCl3) t 6.66 (s, 2H), 3.84 (s, 6H)
70% With bromine; In dichloromethane; at 4 - 20℃; To a stirred solution of <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (9.0 g, 58.7 mmol, 1.0 eq) in 350 mL of anhydrous DCM was dropwise added over 30 min a Bn solution in 50 mL of anhydrous DCM at 4 C. An additional 200 mL was added to the slurry to achieve a semi-homogeneous solution. The reaction mixture was stirred overnight at room temperature. The dark brown mixture was cooled to 4 C and basified by addition of 1.0 M NaOH solution ( ca . 100 mL) to pH = 10-11. The mixture was diluted with 200 mL of DCM and the layers are separated. The aqueous layer was extracted with DCM (200 mL total). The combined DCM layers were washed with water, brine, and dried over NaiSCri. After concentration in vacuo , the crude product was obtained as a slightly reddish solid. The residue was dissolved in DCM (8 mL) and loaded onto a 220 g HP silica gel Gold RediSep column and purified via ISCO (gradient elution: 5 - 95% EA in hexanes), pure fractions combined, and the solvent evaporated in vacuo. The solid was triturated with DCM and hexanes and filtered. The off-while solid was dried in vacuo giving the title compound 26 as an off-white solid (9.4 g, 70%). MS (ESI, pos.): calc’d for CxHioBrNCb, 230.99; found 231.9 and 234.0 (M+H). ‘H NMR (500 MHz; CDCT) S 6.66 (s, 2H), 3.84 (s, 6H).
54.8% Example 10: [(2R,5R)-17,20-Dimethoxy-3,12-dioxo-2-(l-oxo-l,2-dihydro- isoquinolin-7-ylamino)-13-oxa-4,ll-diaza-tricyclo[14.2.2.1 ' jhenicosa- l(19),6,8,10(21),16(20),17-hexaen-5-yl]-acetic acid ethyl ester; <n="132"/>[00281] A solution of bromine (6.6 mL, 127 mmol) in CH2Cl2 (100 mL) was added dropwise to a solution of <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (19.5 g, 127 mmol) in CH2Cl2 (1273 mL) at 0 0C over 5 h. The reaction mixture was stirred for an additional 30 min and then NaOH (1.0 M, 500 mL) was added. The phases were separated and the organic phase was washed with H2O (1x250 mL), brine (1x250 mL), dried over Na2SO4 and concentrated. The crude brown oil was purified by column chromatography (0 to 50% EtOAc in hexanes) to yield 1OA (20 g, 69.8 mmol, 54.8 % yield) as a white solid.

  • 14
  • 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid [ No CAS ]
  • [ 2734-70-5 ]
  • [ 124-40-3 ]
  • 2-[7-chloro-6-{(dimethylamino)methyl}-2-oxo-4-phenyl-2H-chromen-3-yl]-N-(2,6-dimethoxyphenyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% A solution of 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid (0.13 g) in THF (3 ml) was combined with DMF (1 drop) and oxalyl chloride (56 ml), and stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure, and the resultant residue was dissolved in THF (2 ml), and added dropwise to a solution of <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (46 ml) and triethylamine (86 ml) in THF (2 ml) at 0 C. After stirring for 1 hour, the reaction solution was combined with water, and the solution was extracted with ethyl acetate. The extract was washed with a 1 N solution of hydrochloric acid followed by a saturated aqueous solution of sodium chloride, a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, and after drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The resultant residue was dissolved in THF (2 ml), combined with a solution of dimethylamine (200 mg) in THF (1 ml), and stirred overnight. The reaction solution was concentrated under reduced pressure, and the resultant residue was dissolved in ethyl acetate (30 ml), and then washed with a saturated aqueous solution of sodium chloride. After drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The resultant residue was purified by a silica gel column chromatography (eluent: chloroform-methanol-aqueous ammonia=30:1:0.1), and further purified by recrystallization from ethyl acetate to obtain the title compound (81 mg, yield: 50%). [0667] Melting point: 221-223 C. [0668] NMR (CDCl3) δ: 2.17 (6H, s), 3.41 (2H, s), 3.48 (2H, brs), 3.79 (6H, brs), 6.54 (2H, d, J=8 Hz), 7.08 (1H, brs), 7.15 (1H, t, J=8 Hz), 7.35-7.60 (8H, m). [0669] IR(KBr): 1732, 1661, 1560, 1478 cm-1. [0670] Analysis for C28H27N2O5Cl [0671] Calcd (%): C:66.33H:5.37 N:5.53 [0672] Found (%): C:66.17H:5.38 N:5.22
  • 15
  • [ 389081-19-0 ]
  • [ 2734-70-5 ]
  • N-(2,6-dimethoxyphenyl)-2-(2-oxo-4-phenyl-2,6,7,8-tetrahydrocyclopenta[g]chromen-3-yl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% A solution of (2-oxo-4-phenyl-2,6,7,8-tetrahydrocyclopenta[g]chromen-3-yl)acetic acid (150 mg) in THF (10 ml) was combined with dimethylformamide (DMF, 1 drop) and oxalyl chloride (0.06 ml), and stirred at room temperature for 30 minutes. The reaction solution was concentrated under reduced pressure, and the resultant residue was dissolved in THF (10 ml), and added dropwise to a solution of <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (79 mg) and triethylamine (0.1 ml) in THF (5 ml). After stirring at room temperature for 1 hour, the solvent was distilled off under reduced pressure, and the resultant residue was combined with water, and extracted with ethyl acetate. The extract was washed with diluted hydrochloric acid followed by a 1 N solution of sodium hydroxide and water, dried over magnesium sulfate, and then concentrated. The resultant residue was purified by recrystallization from ethyl acetate-THF to obtain the title compound (146 mg, yield: 64%). [0644] Melting point: 213-215 C. [0645] NMR (CDCl3) δ: 2.09 (2H, m), 2.81 (2H, t, J=7 Hz), 2.99 (2H, t, J=7 Hz), 3.46 (2H, br) 3.78 (6H, s), 6.54 (2H, d, J=8 Hz), 6.85 (1H, s), 7.14 (1H, t, J=8 Hz), 7.26 (1H, s), 7.43 (2H, m), 7.50 (1H, m). [0646] IR(KBr): 1707, 1686, 1508 cm-1. [0647] Analysis for C28H25NO5.0.2H2O [0648] Calcd (%): C:73.25H:5.58 N:3.05 [0649] Found (%): C:73.04H:5.79 N:3.14
  • 16
  • 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid [ No CAS ]
  • [ 2734-70-5 ]
  • [ 127-09-3 ]
  • [7-chloro-3-{2-(2,6-dimethoxyanilino)-2-oxoethyl}-2-oxo-4-phenyl-2H-chromen-6-yl]methyl acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
36% A solution of 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid (0.13 g) in THF (3 ml) was combined with DMF (1 drop) and oxalyl chloride (56 ml), and stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure, and the resultant residue was dissolved in THF (2 ml), and added dropwise to a solution of <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (46 ml) and triethylamine (86 ml) in THF (2 ml) at 0 C. After stirring for 1 hour, the reaction solution was combined with water, and the product was extracted with ethyl acetate. The extract was washed with a 1 N solution of hydrochloric acid followed by a saturated aqueous solution of sodium chloride, a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, and after drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The resultant residue was dissolved in DMF (2 ml), combined with anhydrous sodium acetate (150 mg), and stirred at 60 C. for 3 hours. The reaction solution was combined with water, and the product was extracted with ethyl acetate, and the extract was washed with a saturated aqueous solution of sodium chloride. After drying over magnesium sulfate, the solvent was distilled off under reduced pressure, and the resultant residue was purified by recrystallization from THF to obtain the title compound (61 mg, yield: 36%). [0685] Melting point: 229-231 C. [0686] NMR (CDCl3) δ: 1.99 (3H, s), 3.50 (2H, brs), 3.78 (6H, brs), 5.09 (2H, s), 6.55 (2H, d, J=8 Hz), 7.06 (1H, brs), 7.16 (1H, t, J=8 Hz), 7.25-7.60 (8H, m). [0687] IR(KBr): 1737, 1732, 1477, 1260 cm-1. [0688] Analysis for C28H24NO7Cl [0689] Calcd (%): C:64.43H:4.63 N:2.68 [0690] Found (%): C:64.45H:4.95 N:2.64
  • 17
  • [ 391688-50-9 ]
  • [ 2734-70-5 ]
  • N-(2,6-Dimethoxyphenyl)-N'-[3-(2-methylphenyl)-6,7-dihydro-5H-indeno[5,6-b]furan-2-yl]urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% A solution of 3-(2-methylphenyl)-6,7-dihydro-5H-indeno[5,6-b]furan-2-carboxylic acid (3 g), triethylamine (2.2 ml) and DPPA (2.9 ml) in benzene (200 ml) was stirred at room temperature for 1 hour, and then heated under reflux for 1 hour. After cooling to room temperature, to the reaction solution <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (1.6 g) was added and then heated under reflux for 1 hour. The reaction solution was combined with water and chloroform, and the organic layer was washed with diluted hydrochloric acid followed by a saturated aqueous solution of sodium hydrogen carbonate and water, and after drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The resultant residue was purified by a silica gel column chromatography (eluent: chloroform), and further purified by recrystallization from THF-chloroform to obtain the title compound as a colorless crystal (2.4 g, 53%). [0735] Melting point: 270 C. (decomp.). [0736] NMR (CDCl3) δ: 2.11 (2H, m), 2.27 (3H, m), 2.90 (2H, t, J=7 Hz), 2.99 (2H, t, J=7 Hz), 3.71 (6H, s), 6.54 (1H, s), 6.56 (2H, d, J=8 Hz), 6.86 (1 h, bs), 7.06 (1H, s), 7.15 (1H, t, J=8 Hz), 7.33 (5H, m). [0737] IR(KBr): 3241, 1659, 1557 cm-1. [0738] Analysis for C27H26N2O4 [0739] Calcd (%): C:78.28H:5.92 N:6.33 [0740] Found (%): C:73.15H:6.00 N:6.29
  • 18
  • [ 51410-99-2 ]
  • [ 2734-70-5 ]
YieldReaction ConditionsOperation in experiment
93% To a mixture of N-hydroxy-2,6-dimethoxybenzamide (1a) (0.237 g, 1.2 mmol), K2CO3 (0.166 g, 1.2 mmol), and DMSO (0.5 mL) was added acetic anhydride (1.1 mL,0.012 mmol) and heated to 50 C. After stirring at that temperature for 10 min, the reaction mixture was cooled to 0 C and then treated with 2 M HCl (ca. 2mL). After the mixture became the clear solution, 2 M NaOH (ca. 2 mL) was added and extracted with Et2O (15 mL x 3). The combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/Et2O, 1:1) to yield 2,6-dimethoxyaniline (2a) (0.171 g, 93%) as a white crystalline solid.
  • 19
  • [ 2734-70-5 ]
  • [ 3163-15-3 ]
YieldReaction ConditionsOperation in experiment
Step 1. 2-aminobenzene-1,3-diol1.0 M of Boron tribromide in DCM (12 mL, 12 mmol) was added slowly drop-wise to a solution of <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (Alfa Aesar, 0.5 g, 3 mmol) in DCM (5 mL) at -45 C. under nitrogen. The mixture was stirred, with warming to RT, for 3 days. The mixture was cooled in an ice bath and water was added drop-wise. Saturated sodium bicarbonate solution was added to adjust pH to 5-6 and the aqueous phase was extracted with DCM. The aqueous layer, which contained product, was evaporated to afford a solid mixture. The solid was slurried in ethanol and the solids were filtered off. The ethanol solution was used in the next step. 1H NMR (400 MHz, CD3OD): δ 6.68 (t, 1H), 6.37 (d, 2H).
  • 20
  • [ 2734-70-5 ]
  • [ 115483-26-6 ]
YieldReaction ConditionsOperation in experiment
General procedure: To a solution of aniline (0.93 g,10 mmol) in 10% HCl (50 mL) cooled in an ice-bath was added NaNO2 (0.74 g,10.7 mmol). The mixture was stirred at 0 C for 0.5 h and followed by the addition of NaN3 (0.72 g,11 mmol). The mixture was stirred at 0 C for 0.5 h and the aqueous layer was extracted by EtOAc (3×50 mL). The organic layer was dried over MgSO4 overnight. After filtration, EtOAc was evaporated to give 20a as yellow oil (1.09 g, yield 92%), which was used directly in the next reaction without further purification. Compounds 20b-20z and 20aa were prepared from compounds19b-19z and 19aa in a similar manner as described for compound 20a, respectively.
  • 21
  • [ 2734-70-5 ]
  • trans-[tert-butyl N-benzyl-3-(3,4-methylenedioxyphenyl)aziridine-2-carboxylate] [ No CAS ]
  • (±)-tert-butyl 2-benzylamino-3-[(2,6-dimethoxyphenyl)-amino]-3-(3,4-methylenedioxyphenyl)propanoate [ No CAS ]
  • 22
  • 1,3-diphenyl-3-hydroxypropene [ No CAS ]
  • [ 2734-70-5 ]
  • C23H23NO2 [ No CAS ]
  • 23
  • [ 2734-70-5 ]
  • [ 212780-49-9 ]
  • dibenzyl 3-(2,6-dimethoxyphenylcarbamoyl)propylphosphonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: To a 0.5 M solution of the acid 9/10 in dichloromethane under nitrogen atmosphere, was added oxalyl chloride (2 eq.) and a few drops of DMF at room temperature. After effervescence subsided, the mixture was heated to reflux at 45 C for 2 h. It was then cooled to room temperature, concentrated in vacuo, co-evaporated three times with toluene and then re-dissolved in dichloromethane. The aniline (2 eq.) was then added at 0 C, followed by DIPEA (3 eq.) and the mixture stirred overnight at room temperature. The reaction was quenched by addition of NaHCO3 and the aqueous layer was extracted three times with dichloromethane. The combined organic layer was washed once with brine, dried over Na2SO4 and concentrated in vacuo. Purification by silica gel chromatography using a toluene/acetone or dichloromethane/methanol solvent system gave access to the pure protected amides (30%-75% yields).
  • 24
  • [ 23112-96-1 ]
  • [ 2734-70-5 ]
YieldReaction ConditionsOperation in experiment
96% With sodium hydroxide; hydroxylamine-O-sulfonic acid; In water; acetonitrile; for 1h;Sonication; General procedure: Reactions facilitated by sonication were performed on a 1.0 mmol scale. Arylboronic acid 3 (1.0 equiv) and MeCN (5.0 mL) were added to a 25 mL microwave vial equipped with a stir bar, followed by HSA (1.5 equiv) and aq 1 M NaOH (5 equiv). The mixture was capped and set to stir for 5 min, then placed in an ultrasonic cleaner for 30 min (35 kHz, 90 W), at which time the vial was removed and a small aliquot was taken for reaction monitoring via HPLC analysis. The mixture was then placed back in the sonication bath for 30 min. This process was repeated until the reaction had gone to completion, or the reaction failed to progress, as monitored by HPLC. The reaction mixture was diluted with H2O (30 mL) and extracted with EtOAc (2 × 30mL). The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes) to afford the desired amine product 2.
  • 25
  • [ 500-99-2 ]
  • [ 2734-70-5 ]
  • 2,6,2',6'-tetramethoxy-(4-hydroxy)azobenzene [ No CAS ]
  • 26
  • [ 79-37-8 ]
  • [ 2734-70-5 ]
  • C18H20N2O6 [ No CAS ]
  • 27
  • [ 2734-70-5 ]
  • [ 88323-40-4 ]
  • N-(2,6-dimethoxyphenyl)-N'-isopropyl-[1,1'-biphenyl]-2,2'-dicarboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Under argon condition [26], p-TsCl (p-toluenesulfonyl, 1.2 mmol) in 2 mL dichloromethane was injected to the 2 mL dichloromethane mixture of compounds 1-9 (1 mmol) and 4-dimethylaminopyridine (2.4 mmol) at reflux temperature. The aromatic amine or heteroaromatic amine (1.2 mmol) was injected to the reaction mixture 2 h later. The mixture was stirred for another 2 h. After removing solvent in vacuo, the residue was quenched with EtOAc and water, neutralized with sat. NaHCO3 solvent, the EtOAc layer was dried over anhydrous Na2SO4 and concentrated. The residue was chromatographed on silica gel (EtOAc-petroleum ether) to give target compounds. The structures of compounds 1a-9s were showed in the Supporting information.
  • 28
  • [ 50-00-0 ]
  • (+)-pentamethyl-η5-cyclopentadienyl (1-methyl-η5-cyclopenta[b]pyridinyl-3-carbaldehyde)iron [ No CAS ]
  • [ 2734-70-5 ]
  • (+)-ferrocenyl-2,6-dimethoxyphenylimidazolium chloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% A 2 dram vial equipped with a stir bar is charged with formaldehyde (37%, 69.7 mg, 0.859 mmol), THF (4.5 mL), and <strong>[2734-70-5]2,6-dimethoxyaniline</strong> (79.0 mg, 0.515 mmol). The mixture is stirred at ambient temperature for 30 minutes and then HCl (3.0 M in EtOH, 0.329 mL, 0.988 mmol) is added and the mixture is stirred for 30 minutes. (+)-Pentamethyl-η5-cyclopentadienyl(1-methyl-η5-cyclopenta[b]pyridinyl-3-carbaldehyde)iron (3) (150 mg, 0.429 mmol) is then added, and the reaction is allowed to stir at ambient temperature for ˜3 hours while monitoring by TLC analysis (90:10:1, DCM:MeOH:AcOH, Rf˜0.25). The crude residue is purified by flash chromatography on neutral alumina (acetone to 5:1, acetone:EtOH), and then the residue is washed with 5:1 Et2O:EtOAc to afford the NHC as an orange solid (4c') (148 mg, 65%). Analytical data: 1H NMR (500 MHz, Methanol-d4) δ 11.85 (s, 1H), 7.42 (t, J=8.3 Hz, 1H), 7.28 (s, 1H), 6.80 (s, 1H), 6.72 (d, J=8.4 Hz, 2H), 6.32 (s, 1H), 4.11 (d, J=2.3 Hz, 1H), 3.96 (d, J=2.5 Hz, 1H), 3.89 (s, 6H), 2.34 (s, 3H), 1.68 (s, 19H); 13C NMR (126 MHz, CDCl3) δ 154.98, 139.56, 134.01, 132.11, 129.40, 115.50, 113.29, 105.53, 104.93, 89.72, 81.45, 76.65, 73.29, 65.61, 65.03, 56.84, 19.45, 9.83. IR (neat) ν 3022, 2898, 2362, 1624, 1603, 1541, 1258, 1115, 1029, 779 cm-1. LRMS (EI): Mass calcd for C29H33FeN2O2 [M]+, 497.2; found 497.3.
  • 29
  • [ 2734-70-5 ]
  • [ 606-18-8 ]
  • C15H15N3O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; General procedure: To a mixture of benzoic acids 4 (7) (4 mmol),1-ethyl-3-(3-dimethyllaminopropyl) carbodiimide hydrochloride (4.8 mmol) and N-hydroxybenzotrizole (0.48 mmol) wereadded amines (4.8 mmol) at room temperature. The reaction mixture was stirredfor overnight and washed with water successively. The organic layer was driedover anhydrous sodium sulfate. Then the solvent was removed in vacuo to affordcrude compounds 5 (8).
  • 30
  • [ 2734-70-5 ]
  • [ 372-09-8 ]
  • 1,5-bis(2,6-dimethoxyphenyl)-3-cyanoformazan [ No CAS ]
  • 31
  • [ 2734-70-5 ]
  • rac-(2R,3R)-1-(benzo[d][1,3]dioxol-5-yl)-2,3-dimethylpentane-1,4-dione [ No CAS ]
  • 5-(benzo[d][1,3]dioxol-5-yl)-1-(2,6-dimethoxyphenyl)-3,4-dimethyl-1H-pyrrole-2-carbaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
15 mg With oxygen; sodium acetate; acetic acid; at 80℃; for 48h; General procedure: To a solution of diketone (1 mmol) and NaOAc (1.1 mmol) in acetic acid (15 mL) was added dropwise amine (1.1 mmol) dropwise and the resultant mixture was stirred vigorously at 80 C, open to air, for the time stated. Alternatively the reaction was stirred under an atmosphere of nitrogen if specifically stated. The mixture was cooled to room temperature and neutralized to pH 7 using NaOH solution. Ethyl acetate (15 mL) was added, the organic layer separated and the aqueous phase further extracted with ethyl acetate (3×15 mL). The combined organic extracts were dried (MgSO4) and the solvent removed in vacuo. The crude product was then purified by flash chromatography to yield the pyrrole product.
  • 32
  • [ 201230-82-2 ]
  • [ 2734-70-5 ]
  • [ 536-74-3 ]
  • 1-(2,6-dimethoxyphenyl)-3-phenylpyrrolidine-2,5-dione [ No CAS ]
  • 33
  • [ 5779-95-3 ]
  • [ 2734-70-5 ]
  • α,α-bis(4-amino-3,5-dimethoxyphenyl)-1-(3,5-dimethylphenyl)methane [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With hydrogenchloride; In water; at 35 - 50℃; for 6h;Inert atmosphere; Reflux; Equipped with a mechanical stirrer, a condenser and a nitrogen gas through the mouth of the three-necked flask, were added 61.28g (0.40mol) 2,6- dimethoxy aniline and 135.00mL distilled water, stir under a nitrogen atmosphere.40.50mL slowly added dropwise concentrated hydrochloric acid (37% mass fraction), the temperature of the system was maintained at 35 , then portionwise added 28.14g (0.21mol) 3,5- dimethylbenzaldehyde.System under reflux with vigorous stirring After 6h, the reaction system temperature was lowered to 50 , added in portions with stirring 16.40g sodium hydroxide powder.The solution was subjected to steam distillation, after suction filtration to obtain a solid powder.A solid powder with hot water, and dried dioxane was recrystallized, and dried to give α, α- bis (4-amino-3,5-dimethoxyphenyl) -1- (3 ', 5'-A phenyl) methane solid powder 77.56g (92% yield)
  • 34
  • [ 2734-70-5 ]
  • [ 102368-13-8 ]
  • 3-isothiocyanato-2,4-dimethoxypyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% In dichloromethane; at 20℃; for 16.6667h; [015581 3-isothiocyanato-2,4-dimethoxypyridine, Example 771.1. A 2L round bottom flask was charged with 1,1”-thiocarbonyldi-2(1H)-pyridone (47.0 g, 202 mmol) and dissolved in dry DCM (405 mL). To that solution was added 2,6- dimethoxyaniline (31 g, 202 mmol) dissolved in DCM (405 mL) via an addition funnel at RT over 40 minutes. After 16 hours, the reaction was concentrated in vacuo and purified on silica gel (0-20% EtOAc in heptanes) to give 2-isothiocyanato-1,3-dimethoxybenzene (32 g, 164 mmol, 81 % yield). LCMS-ESI (POS.) mlz: 197.1 (M+H)t
  • 35
  • [ 3222-47-7 ]
  • [ 2734-70-5 ]
  • N-(2,6-dimethoxyphenyl)-6-methylnicotinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% [0729j N-(2,6-dimethoxyphenyl)-6-methylnicotinamide, Example 370.1. To a stirred solution of 6-methylnicotinic acid (3.1 g, 22.8 mmol) and TEA (9.5 mL, 68.5 mmol) in DMF (76 mL) was added HATU (9.6 g, 25.1 mmol). After 3 mi 2,6- dimethoxyaniline (3.5 g, 22.9 mmol) was added. The resulting mixture was stirred at RT until LCMS analysis indicated that the reaction was complete. The reaction mixture was quenched using a mixture of saturated aqueous sodium bicarbonate and brine, then was extracted with EtOAc (4X). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: 25-100% EtOAc/hexanes) to provide 370.1 (4.2 g, 68% yield) as atan solid. LCMS-ESI (POS), mlz: 273.2 (M+H).
 

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