22808-73-7|Methyl 4-sulfamoylbenzoate| Ambeed

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Quality Control of [ 22808-73-7 ] Purity: 97% SDS Specification

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Product Details of [ 22808-73-7 ]

CAS No. :	22808-73-7
Formula :	C₈H₉NO₄S
M.W :	215.23
SMILES Code :	O=C(OC)C1=CC=C(S(=O)(N)=O)C=C1
MDL No. :	MFCD03768500
InChI Key :	XLOVNJUCAFIANM-UHFFFAOYSA-N
Pubchem ID :	89847

Safety of [ 22808-73-7 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338

Computational Chemistry of [ 22808-73-7 ] Show Less

Physicochemical Properties

Num. heavy atoms	14
Num. arom. heavy atoms	6
Fraction Csp3	0.12
Num. rotatable bonds	3
Num. H-bond acceptors	5.0
Num. H-bond donors	1.0
Molar Refractivity	48.72
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	94.84 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.31
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	0.64
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.2
Log P_o/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.	0.28
Log P_o/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	-0.14
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.66

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.7
Solubility	4.33 mg/ml ; 0.0201 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.	-2.21
Solubility	1.34 mg/ml ; 0.00621 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	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	-2.05
Solubility	1.93 mg/ml ; 0.00897 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	No
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.	-7.16 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	0.0
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	0.0 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)	1.74

Application In Synthesis of [ 22808-73-7 ]

* 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 [ 22808-73-7 ]

[ 22808-73-7 ] Synthesis Path-Downstream 1~38

1
[ 186581-53-3 ]
[ 138-41-0 ]
[ 22808-73-7 ]

References: [1]Journal of the Chemical Society,1951,p. 1877,1880.
[2]Magnetic Resonance in Chemistry,1989,vol. 27,p. 585 - 591.

2
[ 67-56-1 ]
[ 138-41-0 ]
[ 22808-73-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	With sulfuric acid; for 8h;Reflux;	Commercially available, 73 4-sulfamoylbenzoic acid 5 (10mmol) was refluxed in dried 74 methanol with a catalytic amount of 75 conc. H2SO4 acid for 8h. After completion of the reaction, the mixture was poured into ice cold water and obtained precipitate was filtered and dried to give 11 methyl 4-sulfamoylbenzoate 6. 4.3.2 11 Methyl 4-sulfamoylbenzoate (6) (0035) White crystalline solid; yield 95%; mp: 148-150C; 1H NMR (DMSO-d6,400MHz):delta 3.87 (s, 3H, OCH3), 7.55 (s, 2H, NH2), 7.94 (d, 2H, Ar, J=8.4Hz), 8.12 (d, 2H, Ar, J=8.4Hz); LC-MS: m/z; 216 (M+1).
93%	With sulfuric acid;Reflux;	Concentrated sulfuric acid (1 ml) was added dropwise to a mixture of 4-aminosulfonylbenzoic acid (2.010 g, 10 mmol) in methanol (60 mL) and reacted under reflux until TLC showed the reaction was complete.Then, the solvent was removed under reduced pressure, and the residue was added to an aqueous sodium hydroxide solution to adjust the pH 6-7.The mixture was then stirred and filtered to obtain 2.000 g of white solid with a yield of 93.0%.
92%	With sulfuric acid; at 20℃;Reflux;	4-Sulfamoyl-benzoic acid methyl ester; To a mixture of 5.16 g 4-carboxylbenzenesulfonamide in 150 ml. methanol was added 6.84 ml_ sulfuric acid. The mixture was refluxed overnight and cooled to room temperature. The mixture was evaporated to dryness and the residue was triturated with Et2O. The formed precipitation was filtered off, washed with Et2O and dried to give 5.2 gram (92%) of a white solid. 1H NMR (400 MHz, CDCI3) delta 3.90 (s, 3H), 7.59 (s, 2H), 7.97 (d, J=5.84 Hz, 2H), 8.15 (d, J=5.84 Hz, 2H).

75%	With thionyl chloride; at 0 - 20℃;	To a suspension of 4-(aminosulfonyl)benzoic acid (500 mg, 2.5 mmol) in MeOH (2 ml) at O0C is added thionylchloride (0.2 ml, 7.4 mmol). The reaction mixture is stirred at rt overnight. When TLC confirms the total consumption of the starting acid, the solvent and excess thionyl chloride are removed under reduced pressure to afford 400 mg (75 %) of the title compound, which was used in the next step without any further purification. LC/MS: (ES+):215.9, (ES-):214.1.
	Reflux; Acidic conditions;	Tolylsulfonamide 10 (1.00mM) was first converted to 4-aminosulfonyl benzoic acid by refluxing its aqueous suspension with KMnO4 (3.00mM) to generate the corresponding carboxylic acid followed by refluxing its methanolic solution firstly in acidic condition and then in excess of hydrazine hydrate.37 Yield 74%, lit. mp: 230-232C, Obs. mp: 228-230C.
	With thionyl chloride; at 0 - 40℃; for 2h;	To the solution of 4-sulfamoylbenzoic acid (200 mg, 0.53 mmol) inMeOH (8 mL) added SOCl2 (1348 muL, 1.84 mmol) at 0 C. The mixturewas stirred at 40 C for 2 h, and then concentrated. Ester (214 mg,1.00 mmol) and (Boc)2O (238 mg, 1.09 mmol) were dissolved in DCM(8 mL). Et3N (138 muL, 1 mmol) and DMAP (12.2 mg, 0.1 mmol) wereadded and the mixture was stirred at rt. for 1.5 h. The solution wasconcentrated and purified to afford methyl 4-(N-(tert-butoxycarbonyl)sulfamoyl)benzoate. DIBAL-H (2 mL, 2 mmol) was added slowly tomethyl benzoate (300 mg, 1.00 mmol) in DCM (8 mL) at -78 C and themixture was stirred at -78 C for 2 h. The reaction was quenched by MeOH (2 mL), and then warmed to 0 C and added 10% citric acidunder stirring. The mixture was extracted with DCM, and the organicswere washed, dried, concentrated and purified to afford 4-formylbenzenesulfonamide.Using 4-formylbenzenesulfonamide, thecompound 44 was obtained from 5 by the general procedure as above.To the solution of 44 (95 mg, 0.20 mmol) in DCM (4 mL) added TFA(300 muL, 0.04 mmol). The mixture was stirred at rt. for 1 h. The solutionwas adjusted to pH 7-8 by NaHCO3. The mixture was extracted withEA, and the organics were washed, dried, concentrated and purified toafford 17, 54% yield for five steps, 94.0% HPLC purity.

References: [1]Journal of the American Chemical Society,2006,vol. 128,p. 3273 - 3280.
[2]Journal of Medicinal Chemistry,2010,vol. 53,p. 4555 - 4559.
[3]European Journal of Medicinal Chemistry,2018,vol. 156,p. 430 - 443.
[4]Patent: CN110903262,2020,A .Location in patent: Paragraph 0059-0063.
[5]Patent: WO2009/115515,2009,A1 .Location in patent: Page/Page column 26.
[6]Advanced Synthesis and Catalysis,2020,vol. 362,p. 561 - 571.
[7]Bollettino Chimico Farmaceutico,1997,vol. 136,p. 244 - 249.
[8]Patent: WO2007/23186,2007,A1 .Location in patent: Page/Page column 49.
[9]Tetrahedron,1993,vol. 49,p. 11329 - 11340.
[10],1949,vol. 39,p. 109,112,113.
[11]Kagaku Kenkyusho Hokoku,1950,vol. 26,p. 301,302.
[12]Journal of Medicinal Chemistry,2005,vol. 48,p. 2121 - 2125.
[13]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 3028 - 3036.
[14]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 1873 - 1882.
[15]ACS Medicinal Chemistry Letters,2017,vol. 8,p. 792 - 796.
[16]European Journal of Medicinal Chemistry,2018,vol. 157,p. 28 - 36.
[17]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 1087 - 1098.
[18]European Journal of Medicinal Chemistry,2020,vol. 193.

3
[ 22808-73-7 ]
[ 108-24-7 ]
methyl 4-(N-acetylsulfamoyl)benzoate [ No CAS ]

References: [1]European Journal of Organic Chemistry,2013,p. 5381 - 5386.
[2]Journal of Organic Chemistry,2014,vol. 80,p. 790 - 798.
[3]Journal of Organic Chemistry,2014,vol. 79,p. 8278 - 8287.
[4]Chemical Communications,2019,vol. 55,p. 2027 - 2030.
[5]Kagaku Kenkyusho Hokoku,1950,vol. 26,p. 301,302.

4
[ 110-88-3 ]
[ 22808-73-7 ]
[ 56221-12-6 ]

References: [1]Journal of the Chemical Society. Perkin transactions I,1975,p. 772 - 774.

5
[ 1125-88-8 ]
[ 22808-73-7 ]
[ 155495-85-5 ]

References: [1]Tetrahedron,1993,vol. 49,p. 11329 - 11340.

6
[ 22808-73-7 ]
[ 104-12-1 ]
[ 128924-56-1 ]

References: [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 2393 - 2407.

7
[ 110955-54-9 ]
[ 22808-73-7 ]
[ 67-64-1 ]

References: [1]Journal of Organic Chemistry USSR (English Translation),1987,vol. 23,p. 335 - 342.
Zhurnal Organicheskoi Khimii,1987,vol. 23,p. 375 - 382.

8
[ 22808-73-7 ]
[ 672-65-1 ]
[ 89820-24-6 ]

References: [1]Agricultural and Biological Chemistry,1984,vol. 48,p. 491 - 497.

9
[ 22808-73-7 ]
[ 122-51-0 ]
[ 117662-96-1 ]

References: [1]European Journal of Medicinal Chemistry,1988,vol. 23,p. 97 - 100.

10
[ 22808-73-7 ]
[ 603-35-0 ]
[ 105899-96-5 ]

References: [1]Journal of Organic Chemistry,1987,vol. 52,p. 159 - 163.

11
[ 22808-73-7 ]
[ 111-36-4 ]
[ 88241-94-5 ]

References: [1]Chemical and Pharmaceutical Bulletin,1983,vol. 31,p. 2518 - 2519.

12
[ 22808-73-7 ]
[ 1548-13-6 ]
[ 128924-55-0 ]

References: [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 2393 - 2407.

13
[ 22808-73-7 ]
[ 35264-29-0 ]

Yield	Reaction Conditions	Operation in experiment
90%	With hydrazine hydrate; In 1,4-dioxane; at 100℃; for 8h;	A mixture of <strong>[22808-73-7]methyl 4-sulfamoylbenzoate</strong> 6 (10mmol) and hydrazine hydrate (20mmol) refluxed (100C) in 1,4-dioxane for 8h. Reaction mixture was poured into ice cold water and obtained precipitate was filtered and dried to achieve 4-(hydrazinecarbonyl)benzenesulfonamide in high yield. 4.3.4 13 4-(hydrazinecarbonyl)benzenesulfonamide (7) (0037) White solid; yield 90%; mp: 214-216C; 1H NMR (DMSO-d6,400MHz):delta 4.56 (s, 2H, NH2), 7.47 (s, 2H, NH2), 7.86 (d, 2H, Ar, J=8.4Hz), 7.94 (d, 2H, Ar, J=8.4Hz), 9.95 (s, 1H, NH); LC-MS: m/z; 216 (M+1).
86.4%	With hydrazine hydrate; In methanol; at 50℃;	Hydrazine hydrate (2.33 g, 46.5 mmol) and <strong>[22808-73-7]methyl 4-sulfamoylbenzoate</strong> (2.000 g, 9.3 mmol) were added to methanol (70 ml), and the mixture was stirred at 50 C. until thin layer chromatography showed the reaction was completed.Then, the solvent was removed under reduced pressure, and ethyl acetate (50 ml) was added to the residue. After stirring for 0.5 hours, the mixture was filtered and dried to obtain 1.727 g of white solid with a yield of 86.4%.
	With hydrazine hydrate; In methanol;Reflux;	Tolylsulfonamide 10 (1.00mM) was first converted to 4-aminosulfonyl benzoic acid by refluxing its aqueous suspension with KMnO4 (3.00mM) to generate the corresponding carboxylic acid followed by refluxing its methanolic solution firstly in acidic condition and then in excess of hydrazine hydrate.37 Yield 74%, lit. mp: 230-232C, Obs. mp: 228-230C.

With pyridine; hydrazine hydrate; In ethanol; for 10h;Reflux;

General procedure: To a mixture corresponding ester (9a-n, 5.0 mmol) and hydrazine monohydrate (15.0 mmol) in ethanol, catalytic amount of pyridine (0.5 mL) was added and refluxed for 10 h. The reaction was monitored by TLC. After the completion of the reaction, ethanol was evaporated from the mixture, water was added and extracted using ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and evaporated under vacuum to get the crude mass. Finally, the products 10a-n were purified using column chromatography. (Yield 80-85%).

References: [1]European Journal of Medicinal Chemistry,2018,vol. 156,p. 430 - 443.
[2]Patent: CN110903262,2020,A .Location in patent: Paragraph 0059; 0064-0066.
[3]Journal of the American Chemical Society,2006,vol. 128,p. 3273 - 3280.
[4]Bollettino Chimico Farmaceutico,1997,vol. 136,p. 244 - 249.
[5]Journal of Medicinal Chemistry,2005,vol. 48,p. 2121 - 2125.
[6]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 3028 - 3036.
[7]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 1873 - 1882.
[8]ACS Medicinal Chemistry Letters,2017,vol. 8,p. 792 - 796.
[9]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 2369 - 2374.
[10]European Journal of Medicinal Chemistry,2018,vol. 157,p. 28 - 36.
[11]European Journal of Medicinal Chemistry,2020,vol. 193.

Yield	Reaction Conditions	Operation in experiment
	With ammonium hydroxide; In 1,4-dioxane; water; at 20℃;	General procedure: Toasolutionof2,6- dimethylpyridine-3-sulfonylchloride (500mg,2.4mmol)in1,4-dioxane (5mL)wasaddedammoniawater (2mL),theresultedmixturewasstirredatroomtemperatureforovernight,andthenthesolventwasevaporatedundervacuum,theresiduewaspurifiedbycolumnchromatographyonsilicagel (DCM/methanol30:1)toafford2,6- dimethylpyridine-3-sulfonamide(8.1) (100mg,yield:26)asawhitesolid.m/z:[M+H]+187

15
[ 50-84-0 ]
[ 22808-73-7 ]
4-(2,4-dichloro-benzoylsulfamoyl)-benzoic acid methyl ester [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 5367 - 5380.

16
[ 138-41-0 ]
[ 18107-18-1 ]
[ 22808-73-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	In methanol; hexane; dichloromethane; at 20℃; for 2h;	. To a stirred suspension of 4- [SULFAMOYL-BENZOIC] acid (25.0 g, 0.124 mol) in 4: 1 CH2CI2/MeOH at rt was added 1.0 M TMSCHN2 in hexane (175 mL), and the reaction mixture was allowed to stir for 2 h. The mixture was diluted with 1 N [NAOH] (100 mL) and CH2CI2 (150 mL), and the layers were separated. The organic layer was dried over [NA2SO4,] then filtered, and the solvent was removed under reduced pressure to afford the desired ester (25.2 g, 95%), which was used without further purification. 1H NMR (400 MHz, DMSO-d6) : 8.14 (d, J = 8.1 Hz, 2H), 7.96 (d, J = 8.1 Hz, 2H), 7.58 (s, 2H), 3.90 (s, 3H).
95%		To a stirred suspension of 4-sulfamoyl-benzoic acid (25.0 g, 0.124 mol) in 4:1 CH2CI2/MeOH at rt wasadded 1.0 M TMSCHN2 in hexane (175 ml), and the reaction mixture was20 allowed to stir for 2 h. The mixture was diluted with 1N NaOH (100 ml) andCH2CI2 (150 ml), and the layers were separated. The organic layer was driedover Na2SO4, then filtered, and the solvent was removed under reduced pressure to afford the desired ester (25.2 g, 95%), which was used withoutfurther purification. 1H NMR (400 MHz, DMSO-c/6): 8.14 (d, J = 8.1 Hz, 2H),7.96 (d, J= 8.1 Hz, 2H), 7.58 (s, 2H), 3.90 (s, 3H).
	In methanol; hexane; dichloromethane; for 2h;	A. 4-Sulfamoyl-benzoic acid methyl ester. To a stirred suspension of 4-sulfamoyl-benzoic acid (25.0 g, 0.124 mol) in 4:1 CH2Cl2/MeOH at rt was added 1.0 M TMSCHN2 in hexane (175 mL), and the reaction mixture was allowed to stir for 2 h. The mixture was diluted with 1 N NaOH (100 mL) and CH2Cl2 (150 mL), and the layers were separated. The organic layer was dried over Na2SO4, then filtered, and the solvent was removed under reduced pressure to afford the desired ester (25.2 g, 95%), which was used without further purification. 1H NMR (400 MHz, DMSO-d6): 8.14 (d, J=8.1 Hz, 2H), 7.96 (d, J=8.1 Hz, 2H), 7.58 (s, 2H), 3.90 (s, 3H).

References: [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 5367 - 5380.
[2]Patent: WO2004/7463,2004,A1 .Location in patent: Page 171-172.
[3]Patent: WO2005/5393,2005,A2 .Location in patent: Page/Page column 171-172.
[4]Patent: US2006/4195,2006,A1 .Location in patent: Page/Page column 74-75.

17
[ 22808-73-7 ]
[ 106-96-7 ]
[ 768387-53-7 ]

References: [1]Angewandte Chemie - International Edition,2004,vol. 43,p. 3928 - 3932.

18
[ 648869-31-2 ]
[ 22808-73-7 ]
[ 648869-34-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	With dmap; N-ethyl-N,N-diisopropylamine; bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate; In dichloromethane; at 20℃;	TO A] stirred solution of 4-sulfamoyl-benzoic acid methyl ester (6.01 g, 27.8 [MMOL),] 4- oxo-2-m-tolyl-pentanoic acid (6.35 g, 30.7 mmol), N, N-diisopropylethylamine (12.2 mL, 69.5 [MMOL),] and DMAP (5 mole %) in CH2Cl2 (275 mL) at rt under N2 was added [BROMO-TRIPYRROLIDINO-PHOSPHONIUM] hexafluorophosphate (PyBroP) (18.1 g, 38.9 [MMOL),] and the reaction mixture was allowed to stir overnight. The mixture was diluted with [1 M HCI] (100 mL) and [CH2CI2] (150 mL), and the layers were separated. The organic phase was washed with 1 M HCI (1 x 100 mL), 1N NaOH (1 x 100 mL) and brine [(1] x 100 mL). The organic layer was dried over [NA2SO4,] and then filtered, and the solvent was removed under reduced pressure. Purification on silica gel (0-15% EtOAc in hexane) gave 12.0 g (99%) of desired ester as a white [SOLID.'H] NMR (400 MHz, [CDCI3)] : 8.15 (d, [J=8. 6HZ,] 2H), 7.99 (d, [J=8. 6HZ,] 2H), 7.18 (t, J = 7.6 Hz, 1H), 7.10 (d, J = 7.6 Hz, 1 H), 6.87 (m, 2H), 3.97 (s, 3H), 3.93 (dd. J = 4.3 and 9.5 Hz, 1 H), 3.29 (dd. J = 9.5 and 18.1 Hz, 1 H), 2.60 (dd. J = 4.3 and 18.1 Hz, [1H),] 2.28 (s, 3H), 2.07 (s, 3H).
99%	With dmap; N-ethyl-N,N-diisopropylamine; bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate; In dichloromethane; at 20℃;	To astirred solution of 4-sulfamoyl-benzoic acid methyl ester (6.01 g, 27.8 mmol), 4-oxo-2-/r/-to.yi-pentanoic acid (6.35 g, 30.7 mmol), /V,A/-diisopropylethylamine(12.2 mL, 69.5 mmol), and DMAP (5 mole %) in CH2CI2 (275 ml) at rt under N2was added bromo-tripyrrolidino-phosphonium hexafluorophosphate (PyBroP)10 (18.1 g, 38.9 mmol), and the reaction mixture was allowed to stir overnight.The mixture was diluted with 1M HCI (100 ml) and CH2CI2 (150 ml), and thelayers were separated. The organic phase was washed with 1M HCI (1 x 100mL), 1N NaOH (1 x 100 ml) and brine (1 x 100 rnL). The organic layer wasdried over NajSCU, and then filtered, and the solvent was removed under15 reduced pressure. Purification on silica gel (0-15% EtOAc in hexane) gave12.0 g (99%) of desired ester as a white solid. 1H NMR (400 MHz, CDCI3):8.15 (d, J = 8.6 Hz, 2H), 7.99 (d, J = 8.6 Hz, 2H), 7.18 (t, J = 7.6 Hz, 1H), 7.10(d, J = 7.6 Hz, 1H), 6.87 (m, 2H), 3.97 (s, 3H), 3.93 (dd. J = 4.3 and 9.5 Hz,1H), 3.29 (dd. J = 9.5 and 18.1 Hz, 1H), 2.60 (dd. J = 4.3 and 18.1 Hz, 1H),20 2.28 (s, 3H), 2.07 (s, 3H).
99%	With N-ethyl-N,N-diisopropylamine; bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate;dmap; In dichloromethane; at 20℃;	B. 4-(4-Oxo-2-m-tolyl-pentanoylsulfamoyl)-benzoic acid methyl ester. To a stirred solution of 4-sulfamoyl-benzoic acid methyl ester (6.01 g, 27.8 mmol), 4-oxo-2-m-tolyl-pentanoic acid (6.35 g, 30.7 mmol), N,N-diisopropylethylamine (12.2 mL, 69.5 mmol), and DMAP (5 mole %) in CH2Cl2 (275 mL) at rt under N2 was added bromo-tripyrrolidino-phosphonium hexafluorophosphate (PyBroP) (18.1 g, 38.9 mmol), and the reaction mixture was allowed to stir overnight. The mixture was diluted with 1 M HCl (100 mL) and CH2Cl2 (150 mL), and the layers were separated. The organic phase was washed with 1 M HCl (1100 mL), 1N NaOH (1100 mL) and brine (1*100 mL). The organic layer was dried over Na2SO4, and then filtered, and the solvent was removed under reduced pressure. Purification on silica gel (0-15% EtOAc in hexane) gave. 12.0 g (99%) of desired ester as a white solid. 1H NMR (400 MHz, CDCl3): 8.15 (d, J=8.6 Hz, 2H), 7.99 (d, J=8.6 Hz, 2H), 7.18 (t, J=7.6 Hz, 1H), 7.10 (d, J=7.6 Hz, 1H), 6.87 (m, 2H), 3.97 (s, 3H), 3.93 (dd. J=4.3 and 9.5 Hz, 1H), 3.29 (dd. J=9.5 and 18.1 Hz, 1H), 2.60 (dd. J=4.3 and 18.1 Hz, 1H), 2.28 (s, 3H), 2.07 (s, 3H).

References: [1]Patent: WO2004/7463,2004,A1 .Location in patent: Page 172.
[2]Patent: WO2005/5393,2005,A2 .Location in patent: Page/Page column 172.
[3]Patent: US2006/4195,2006,A1 .Location in patent: Page/Page column 75.
[4]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 77 - 80.

19
[ 22808-73-7 ]
4-(4-oxiranylmethoxy-benzylidene-hydrazinocarbonyl)-benzenesulfonamide [ No CAS ]

References: [1]Journal of the American Chemical Society,2006,vol. 128,p. 3273 - 3280.

20
[ 22808-73-7 ]
C₁₄H₁₃BrN₄O₄S [ No CAS ]