53595-65-6|5-Bromothiophene-2-sulfonamide| Ambeed

Structure of 53595-65-6

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Quality Control of [ 53595-65-6 ] Purity: 97% SDS Specification

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Product Details of [ 53595-65-6 ]

CAS No. :	53595-65-6
Formula :	C₄H₄BrNO₂S₂
M.W :	242.11
SMILES Code :	O=S(C1=CC=C(Br)S1)(N)=O
MDL No. :	MFCD00067990
InChI Key :	WXJQQLDICAOBJB-UHFFFAOYSA-N
Pubchem ID :	1241304

Safety of [ 53595-65-6 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P301+P312-P302+P352-P304+P340-P305+P351+P338

Computational Chemistry of [ 53595-65-6 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	5
Fraction Csp3	0.0
Num. rotatable bonds	1
Num. H-bond acceptors	3.0
Num. H-bond donors	1.0
Molar Refractivity	43.01
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	96.78 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.8
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	1.24
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.24
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.	0.01
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	1.55
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.17

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.43
Solubility	0.907 mg/ml ; 0.00375 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.87
Solubility	0.326 mg/ml ; 0.00135 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	-2.09
Solubility	1.96 mg/ml ; 0.00809 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.	-6.9 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	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)	2.91

Application In Synthesis of [ 53595-65-6 ]

* 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 [ 53595-65-6 ]

[ 53595-65-6 ] Synthesis Path-Downstream 1~36

1
[ 55854-46-1 ]
[ 53595-65-6 ]

Yield	Reaction Conditions	Operation in experiment
76.66%	With ammonia; In tetrahydrofuran; at -78℃; for 3h;	To solution of 3, 5-dichlorothiophene-2-sulfonyl chloride (6.2 g, 23.70 mmol) in THF (10 mL), saturated ammonia solution in THF (60 mL) was added at -78 C. The solid precipitated out and evaporated to dryness and the crude triturated with pentane to obtain the title compound, lnt-B-2.15 (4.4 g, 76.66 %). LCMS ESI(-ve) (m/z): 240.0 (M-2).
68%	With ammonia; In 1,4-dioxane; water monomer; at 0℃; for 0.5h;	(143e) 5-Bromothiophene-2-sulfonamide 5-Bromothiophene-2-sulfonyl chloride (0.30 g, 1.2 mmol) was dissolved in 1,4-dioxane (2 mL). The resulting mixture was stirred at 0C, and 28% ammonia water (4 mL) was added thereto. The resulting mixture was stirred at 0C for 30 min. The reaction solvent was evaporated under reduced pressure, and water was added to the residue. After extraction with methylene chloride, the organic layer was washed with water and brine, and then dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to obtain 0.19 g (yield: 68%) of a crude product of the title compound as a white solid. 1H-NMR (400 MHz, CDCl3) δ ppm: 7.42 (1H, m), 7.06 (1H, m), 5.02 (2H, s).
	With ammonia; at 15℃; for 0.2h;	To a solution of 5-bromothiophene-2-sulfonyl chloride (2 g, 7.65 mmol, 1 eq) in ammonia (1.95 g, 115 mmol, 1.92 mL, 15 eq). The mixture was stirred at 15 C for 0.2 hour. TLC (petroleum ether/EtOAc = 3/1) indicated 5-bromothiophene-2-sulfonyl chloride was consumed completely and new spot formed. The reaction mixture was concentrated under reduced pressure to give a residue. The mixture was dissolved in EtOAc (20 mL), and then strried at 20 C for 5 mins. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to give desired 5-bromothiophene-2-sulfonamide (1.5 g, crude) as a white solid.

With ammonia; at 15℃; for 0.2h;

To a solution of 5-bromothiophene-2-sulfonyl chloride (2 g, 7.65 mmol, 1 eq) in ammonia (1.95 g, 115 mmol, 1.92 mL, 15 eq). The mixture was stirred at 15 C for 0.2 hour. TLC (petroleum ether/EtOAc = 3/1) indicated 5-bromothiophene-2-sulfonyl chloride was consumed completely and new spot formed. The reaction mixture was concentrated under reduced pressure to give a residue. The mixture was dissolved in EtOAc (20 mL), and then strried at 20 C for 5 mins. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to give desired 5-bromothiophene-2-sulfonamide (1.5 g, crude) as a white solid.

References: [1]Organic Process Research and Development,2009,vol. 13,p. 255 - 262.
[2]Journal of Medicinal Chemistry,2018,vol. 61,p. 4860 - 4882.
[3]Patent: WO2021/123237,2021,A1 .Location in patent: Page/Page column 217.
[4]Patent: EP1798229,2007,A1 .Location in patent: Page/Page column 144.
[5]Justus Liebigs Annalen der Chemie,1934,vol. 512,p. 136,156.
[6]Patent: WO2022/76383,2022,A1 .Location in patent: Paragraph 00541.
[7]Patent: WO2022/76383,2022,A1 .Location in patent: Paragraph 00541.

2
[ 53595-65-6 ]
[ 371-42-6 ]
[ 63031-85-6 ]

References: [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 959 - 964.

3
[ 53595-65-6 ]
[ 696-63-9 ]
[ 77893-72-2 ]

References: [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 959 - 964.

4
[ 53595-65-6 ]
[ 2037-31-2 ]
[ 63031-86-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; N,N-dimethyl-formamide; at 130 - 150℃; for 0.75h;Microwave irradiation;	INTERMEDIATE 29; This shows the preparation of 5-[(3-chlorophenyl)thio]thiophene-2-sulfonamide,To a solution of 3-chlorobenzenethiol (87 mg) and 5-bromothiophene-2-sulfonamide (121 mg) in DMF (1 mL) was added aqueous 2 N sodium hydroxide solution (100 μL) and water (1 mL). The reaction was heated in a CEM Discover microwave for 15 rain at 130 C, then for a further 30 min at 150 C. The dark solution was partitioned between diethyl ether and water, and the organic phase was dried over sodium sulfate and concentrated in vacuo. The crude residue was purified by RPHPLC (Xterra, 5% to 95% acetonitrile in TFA (0.2% aq.)) to give the title compound 5-[(3- chlorophenyl)thio]thiophene-2-sulfonamide (35 mg).1H NMR (300 MHz, DMSO) δ 7.79 (s, 2H), 7.56 (d, 1H), 7.47 (d, 1H), 7.44 - 7.35 (m, 3H), 7.30 - 7.26 (m, 1H).

References: [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 959 - 964.
[2]Patent: WO2006/75955,2006,A1 .Location in patent: Page/Page column 45.

5
[ 53595-65-6 ]
[ 1122-97-0 ]
[ 63031-87-8 ]

References: [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 959 - 964.

6
[ 53595-65-6 ]
[ 937-00-8 ]
[ 63032-30-4 ]

References: [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 959 - 964.

7
[ 53595-65-6 ]
[ 2557-77-9 ]
[ 63032-19-9 ]

References: [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 959 - 964.

8
[ 53595-65-6 ]
[ 637-89-8 ]
[ 63032-04-2 ]

References: [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 959 - 964.

9
[ 53595-65-6 ]
[ 2182-85-6 ]
[ 63032-20-2 ]

References: [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 959 - 964.

10
[ 53595-65-6 ]
[ 4637-24-5 ]
[ 104438-09-7 ]

Yield	Reaction Conditions	Operation in experiment
	In DMF (N,N-dimethyl-formamide); at 20℃; for 16h;	Add dimethoxymethyl-dimethyl-amine (1.05 mL, 7.66 mmol) to a solution of 5-BROM- thiophene-2-sulfonic acid amide (1.8 g, 7.43 mmol) in DMF (3 mL) at r. t. for 16 h. Pour reaction mixture into saturated sodium chloride, extract with ethylacetate. Wash combined organic layers with water, dry over sodium sulfate and remove solvent to obtain 2.52 g product. MS (m/e): 297.0/299. 0 (M+H).
	In DMF (N,N-dimethyl-formamide); at 20℃;	to a solution of 5-bromo-2-thiophen sulfonamide (0.3 g, 1.24 mmol) in abs. DMF (3 ml) was added N, N-DIMETHYLFORMAMIDE dimethylacetal (0.17 ml, 1.24 mmol), and the reaction mixture was stirred at ambient temperature overnight. Aqueous work-up, extraction with ethyl acetate, drying over sodium sulfate and evaporation gave the crude product as a colorless crystalline solid.

References: [1]Journal of Medicinal Chemistry,1991,vol. 34,p. 3098 - 3105.
[2]Patent: WO2004/63179,2004,A1 .Location in patent: Page 63.
[3]Patent: WO2004/63194,2004,A1 .Location in patent: Page 42.

11
[ 53595-65-6 ]
[ 108-98-5 ]
[ 63031-79-8 ]

References: [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 959 - 964.

12
[ 53595-65-6 ]
[ 106-53-6 ]
[ 63031-82-3 ]

References: [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 959 - 964.

13
[ 53595-65-6 ]
[ 106-45-6 ]
[ 63031-80-1 ]

References: [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 959 - 964.

14
[ 53595-65-6 ]
[ 106-54-7 ]
[ 63031-81-2 ]

References: [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 959 - 964.

15
[ 53595-65-6 ]
[ 2396-68-1 ]
[ 63032-18-8 ]

References: [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 959 - 964.

16
[ 53595-65-6 ]
[ 137-06-4 ]
[ 63031-84-5 ]

References: [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 959 - 964.

17
[ 53595-65-6 ]
[ 1193-02-8 ]
[ 63031-88-9 ]

References: [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 959 - 964.

18
[ 53595-65-6 ]
[ 1126-81-4 ]
[ 63031-83-4 ]

References: [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 959 - 964.

19
[ 53595-65-6 ]
[ 122775-35-3 ]
[ 959144-38-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 100℃;Inert atmosphere; Sealed tube;	Preparative Example 24PREPARATION OF 5-(3,4-DIMETHOXYPHENYL)THIOPHENE-2-SULFONAMIDEA stirred solution of 5-bromothiophene-2-sulfonamide (2 g, 8.26 mmol) and (3,4-dimethoxyphenyl)boronic acid (1.8 g, 9.90 mmol) in 30 mL DMF at room temperature was purged with N2 gas for 10 mins. To this stirred solution was added (Ph3P)4Pd (1.9 g, 1.65 mmol) and saturated Na2CO3/H2O (2.63 g, 3 mmol). The N2 purge was stopped and the reaction mixture was sealed and heated with a preheated oil bath at 100 C. overnight. The reaction mixture was filtered and the filtrate was partitioned between saturated NaHCO3 and EtOAc, the layers were separated, and the aqueous layer was extracted again with EtOAc. The combined organic layers were dried (MgSO4), filtered, and evaporated in vacuo. The resulting material was purified by silica gel chromatography (40% EtOAc in hexane) to provide the product, as a light yellow solid.1H NMR (500 MHz, CD3OD) δ (ppm): 7.56 (d, 1H), 7.30 (d, 1H), 7.24 (m, 2H), 7.00 (d, 1H), 3.90 (d, 6H).
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 20 - 100℃;Sealed tube;	PREPARATIVE EXAMPLE 10 PREPARATION OF 5-(3,4-DIMETHOXYPHENYL)THTOPHENE-2-SULFON AMIDEA stirred solution of 5-bromothiophene-2-suIfonamide (2 g, 8.26 mmol) and (3,4- dimethoxyphenyl)boronic acid (1.8 g, 9.90 mmol) in 30 mL DMF at room temperature was purged with N2 gas for 10 mins. To this stirred solution was added (Ph3P)4Pd (1.9 g, 1.65 mmol) and saturated Na2CO3/H2θ (2.63 g, 3 mmol). The N2 purge was stopped and the reaction mixture was sealed and heated with a preheated oil bath at 1000C overnight. The reaction mixture was filtered and the filtrate was partitioned between saturated NaHCO3 and EtOAc, the layers were separated, and the aqueous layer was extracted again with EtOAc. The combined organic layers were dried (MgSO^), filtered, and evaporated in vacuo. The resulting material was purified by silica gel chromatography (40% EtOAc in hexane) to provide the product, as a light yellow solid.1H NMR (500 MHz, CD3OD) δ (ppm): 7.56 (d, IH), 7.30 (d, IH), 7.24 (m, 2H), 7.00 (d, IH), 3.90 (d,SH).

References: [1]Patent: US2010/279983,2010,A1 .Location in patent: Page/Page column 18.
[2]Patent: WO2007/139729,2007,A1 .Location in patent: Page/Page column 25.

20
[ 53595-65-6 ]
[ 1001076-50-1 ]
C₂₁H₂₇N₃O₃S₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃;	A mixture of intermediate (9) (0.002 mol) and <strong>[53595-65-6]5-bromo-2-thiophenesulfonamide</strong> (0.0025 mol) in dioxane (40 ml) was degassed and a flow of nitrogen was brought over the reaction mixture (3 times). Then CS2CO3 (0.004 mol) was added and the mixture was degassed and nitrogen was brought over the reaction mixture again, (twice). Then Pd2(dba)3 (0.0001 mol) and Xantphos (0.0001 mol) were added and degassing and the nitrogen action were performed (twice). A nitrogen balloon was left on the reaction mixture and the mixture was stirred overnight at 1000C. The mixture was cooled, filtered and the filtrate was evaporated, yielding intermediate (25).
	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane;Inert atmosphere;	Example A.8 Preparation of [0178] [0179] A mixture of intermediate (9) (0.002 mol) and <strong>[53595-65-6]5-bromo-2-thiophenesulfonamide</strong> (0.0025 mol) in dioxane (40 ml) was degassed and a flow of nitrogen was brought over the reaction mixture (3 times). Then Cs2CO3 (0.004 mol) was added and the mixture was degassed and nitrogen was brought over the reaction mixture again. (twice). Then Pd2(dba)3 (0.0001 mol) and Xantphos (0.0001 mol) were added and degassing and the nitrogen action were performed (twice). A nitrogen balloon was left on the reaction mixture and the mixture was stirred overnight at 100 C. The mixture was cooled, filtered and the filtrate was evaporated, yielding intermediate (25).

References: [1]Patent: WO2008/3665,2008,A1 .Location in patent: Page/Page column 31.
[2]Patent: US2013/324529,2013,A1 .Location in patent: Paragraph 0178; 0179.

21
[ 53595-65-6 ]
[ 661-69-8 ]
[ 778646-79-0 ]

Yield	Reaction Conditions	Operation in experiment
28%	With triphenylphosphine;bis(dibenzylideneacetone)-palladium(0); In toluene; at 120℃; for 2h;	To a degassed suspension of 5-bromo-thiophene-2-sulfonic acid amide (500 mg, 2.07 mmol) in 10 ml toluene were added bis (dibenzylideneacetone) palladium (47 mg, 0.083 MMOL), triphenylphosphine (87 mg, 0.33 mmol) and hexamethyldistannane (812 mg, 2.48 MMOL). The mixture was stirred at 120 C for 2 hours. The reaction mixture was filtered through Celite, washed with water, dried and concentrated. The residue was purified by chromatography on silica gel (cyclohexane/EtOAc: 2/1). Yield: 190 mg (28%).

References: [1]Patent: WO2004/89913,2004,A1 .Location in patent: Page 53; 54.

22
[ 53595-65-6 ]
[ 1074-36-8 ]
[ 900814-30-4 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 30; This shows the preparation of 4-[5-(aminosulfonyl)-2-thienyl]thio}benzoic acid.To a solution of 5-bromothiophene-2-sulfonamide (242 mg) and 4-mercaptobenzoic acid (154 mg) in DMF (1 mL) was added aqueous 2 N sodium hydroxide solution (1 mL). The reaction mixture was heated in a CEM Discover microwave at 150C for 25 min. After this time it was allowed to cool, then it was diluted with water (20 mL) and acidified with 10 % v/v aqueous hydrochloric acid. The fine precipitate that formed was difficult to filter so the EPO <DP n="47"/>majority of the liquid was decanted from the solid, and the gelatinous residue concentrated to dryness in vacuo to give the title compound 4-[5-(aminosulfonyl)-2- thienyl]thio}benzoic acid (280mg).1H NMR (300 MHz, DMSO) δ 13.03 (s, 1H), 7.91 (d, 2H), 7.85 (s, 2H), 7.59 (d, 1H), 7.50 (d, 1H), 7.34 (d, 2H).
	With sodium hydroxide; In water; N,N-dimethyl-formamide; at 150℃; for 0.416667h;Microwave;	This shows the preparation of 4-[5-(aminosulfonyl)-2-thienyl]thio}benzoic acid.I0 To a solution of 5-bromothiophene-2-sulfonamide (242 mg) and 4-mercaptobenzoic acid (154 mg) in DMF (1 mL) was added aqueous 2 N sodium.hydroxide solution (1 mL). The reaction mixture was heated in a CEM Discover microwave at 1500C for 25 min. After this time it was allowed to cool, then it was diluted with water (20 mL) and acidified with 10% v/v aqueous hydrochloric acid. The fine precipitate that formed was difficult to filter is so the majority of the liquid was decanted from the solid, and the gelatinous residue concentrated to dryness in vacuo to give the title compound 4-[5-(aminosulfonyl)-2- thienyl]thio}benzoic acid (280 mg).1HNMR (300 MHz, DMSO) δ 13.03 (s, IH), 7.91 (d, 2H), 7.85 (s, 2H), 7.59 (d, IH), 7.50 (d, IH), 7.34 (d, 2H).

References: [1]Patent: WO2006/75955,2006,A1 .Location in patent: Page/Page column 45-46.
[2]Patent: WO2006/85815,2006,A1 .Location in patent: Page/Page column 42.

23
[ 53595-65-6 ]
[ 4637-24-5 ]
[ 900814-14-4 ]

Yield	Reaction Conditions	Operation in experiment
93%	In acetonitrile; at 20℃; for 24h;	To a solution of 5-bromothiophene-2-sulfonamide (1) (7.00 g, 28.91 mmol) in acetonitrile (50 mL) N,N-dimethylformamide dimethyl acetal (5.50 mL, 41.34 mmol) was added. The mixture was stirred at room temperature for 24 h. Solvent evaporation in vacuum afforded 2 (7.98 g, 93%) as light yellow solid. Mp 104-105 C. IR (KBr, cm-1) νmax: 1631 (N=C), 1331 (S=O), 1142 (S=O), 1127 (S=O); 1H NMR (400 MHz, DMSO-d6) δ: 2.94 (s, 3H), 3.16 (s, 3H), 7.27 (d, J = 3.9 Hz, 1H), 7.36 (d, J = 3.9 Hz, 1H), 8.21 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 35.3, 41.1, 117.1, 130.6, 131.0, 145.7, 160.0.
	In acetonitrile; for 20h;	INTERMEDIATE 11; This shows the preparation of 5-bromo-N-[(1E)-(dimethylamino)methylene]-thiophene-2- sulfonamide.To a stirred solution of 5-bromthiophene-2-sulfonamide (2 g) in acetonitrile (20 mL) was added DMF-DMA (2.24 mL) dropwise. After 20 h the mixture was concentrated in vacuo, and the waxy solid slurried in water and collected by filtration. The solid was washed with EPO <DP n="37"/>water and air dried to give the title compound 5-bromo-N-[(1E)-(dimethylamino) methylene]thiophene-2-sulfonamide (2.3 g).1H NMR (400 MHz, DMSO) δ 8.21 (s, 1H), 7.35 (d, 1H), 7.26 (d, 1H), 3.16 (s, 3H), 2.93 (s, 3H).
	In acetonitrile; for 20h;	This shows the preparation of 5-bromo-Λ/-[(lE)-(dimethylamino)methylene]-thiophene-2- sulfonamide. EPO <DP n="41"/>To a stirred solution of 5-bromothiophene-2-sulfonamide (2 g) in acetonitrile (20 mL) was added DMF-DMA (2.24 mL) dropwise. After 20 h the mixture was concentrated in vacuo, and the waxy solid slurried in water and collected by filtration. The solid was washed with water and air dried to give the title compound 5-bromo-iV-[(lE)-(dimethylamino) methylene]thiophene-2-sulfonamide (2.3 g).1H NMR (400 MHz, DMSO) δ 8.21 (s, IH), 7.35 (d, IH), 7.26 (d, IH), 3.16 (s, 3H), 2.93 (s, 3H).

In water; acetonitrile;

Step A Preparation of N,N-Dimethyl-N'-(5-bromothiophene-2-sulfonyl)formamidine To a stirred mixture of 5-bromothiophene-2-sulfonamide (24.2 g, 0.10 mol) in acetonitrile (100 ml) was added dimethylformamide dimethyl acetal (14 ml) in acetonitrile (125 ml) dropwise over 0.5 hour. After an additional 0.5 hour the solvent was removed in vacuo. The residue was treated with water and the solid that precipitated was collected and dried, 28.7 g., m.p. 103-105 C. Recrystallization from 1-chlorobutane gave material with m.p. 104-106 C. Anal. Calc'd. for C7 H9 BrN2 O2 S2 (297.21): C, 28.29; H, 3.05; N, 9.43. Found: C, 28.07; H, 3.03; N, 9.53.

References: [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 5130 - 5138.
[2]Patent: WO2006/75955,2006,A1 .Location in patent: Page/Page column 35-36.
[3]Patent: WO2006/85815,2006,A1 .Location in patent: Page/Page column 39-40.
[4]Patent: US4721794,1988,A .

24
[ 6320-03-2 ]
[ 53595-65-6 ]
[ 63031-97-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; N,N-dimethyl-formamide; at 130 - 150℃; for 0.416667h;Microwave irradiation;	EXAMPLE 19; This example illustrates the preparation of N-({5-[(2-chlorophenyl)thio]-2- thienyl}sulfonyl)-2-(3-methyl-1-phenyl-1H-pyrazol-5-yl)acetamide. EPO <DP n="65"/>To a solution of 2-chlorothiophenol (87 mg) and 5-bromothiophene-2-sulfonamide (121 mg) in DMF (1 mL) was added 2 N aqueous sodium hydroxide (100μL) and water (1 mL). The reaction mixture was heated in a CEM Discover microwave at 130 C for 5 min, then 150 C for 20 min. The mixture was partitioned between diethyl ether and water, and the organic phase was dried over sodium sulfate, filtered, and concentrated in vacuo. The resultant oil was purified by RPHPLC (Xterra, 5% to 95% acetonitrile in TFA (0.2% aq.)> to give a small amount of 5-[(2-chlorophenyl)thio]thiophene-2-sulfonamide (22 mg) that was dissolved in DCM (2 mL). To this solution was added Intermediate 2 (15 mg), EDCI (17 mg) and DMAP (3 mg). The reaction mixture was stirred for 3 h, then concentrated in vacuo and the residue purified by RPHPLC (Xterra, 5% to 95% acetonitrile in TFA (0.2% aq.)) to give the title compound N-( {5-[(2-chlorophenyl)thio]-2-thienyl} sulfonyl)-2-(3 - methyl- 1 -phenyl-1H-pyrazol-5-yl)acetamide (17 mg). 1H NMR (300 MHz, DMSQ) δ 7.70 (d, 1H), 7.59 (dd, 1H), 7.46 (d, 1H), 7.41 - 7.25 (m, 7H), 7.16 (d, 1H), 6.08 (s, 1H), 3.73 (s, 2H), 2.17 (s, 3H); APCI-MS: m/z 502, 504 [M- H]-.

References: [1]Patent: WO2006/75955,2006,A1 .Location in patent: Page/Page column 63-64.

25
[ 900814-05-3 ]
[ 53595-65-6 ]
N-[(5-bromo-2-thienyl)sulfonyl]-2-(3-methyl-1-phenyl-1H-pyrazol-5-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; In dichloromethane; at 20℃; for 24h;	EXAMPLE 18; This example illustrates the preparation of N-[(5-bromo-2-thienyl)sulfonyl]-2-(3-methyl- 1 -phenyl- 1H-pyrazol-5-yl)acetamide.To a stirred solution of 5-bromothiophene-2-sulfonamide (2.42 g) and Intermediate 2 (2.16 g) in DCM (50 mL) was added EDCI (2.49 g) and DMAP (2 mg). The reaction was stirred for 4 h at RT and more EDCI (500 mg) and DMAP (10 mg) were added. The reaction was stirred for 20 h then partitioned between DCM and 0.5% v/v aqueous hydrochloric acid. The organic phase was dried over sodium sulfate and concentrated in vacuo to give a foam. Ethyl acetate was added until the foam had just dissolved, and iso-hexane added dropwise until a solid began to form. Trituration yielded the title compound N-[(5-bromo-2- thienyl)sulfonyl]-2-(3-methyl-1-phenyl-1H-pyrazol-5-yl)acetamide (2.4 g). 1H NMR (300 MHz, DMSQ) δ 7.53 (d, 1H), 7.43 - 7.31 (m, 4H), 7.30 - 7.25 (m, 2H), 6.09 (s, 1H), 3.76 (s, 2H), 2.18 (s, 3H); APCI-MS: m/z 438, 440 [M-H]-.

References: [1]Patent: WO2006/75955,2006,A1 .Location in patent: Page/Page column 63.

26
(1S,2R)-4-(2-Hydroxy-1-methyl-4-pyridin-3-yl-butoxy)benzeneboronic acid [ No CAS ]
[ 53595-65-6 ]
[ 497-19-8 ]
(1S,2R)-5-[4-(2-Hydroxy-1-methyl-4-pyridin-3-yl-butoxy)-phenyl]-thiophene-2-sulfonic acid amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	tetrakis(triphenylphosphine)palladium (0); In ethanol;	b (1S,2R)-5-[4-(2-Hydroxy-1-methyl-4-pyridin-3-yl-butoxy)-phenyl]-thiophene-2-sulfonic acid amide 2M Aqueous sodium carbonate (0.75 ml), (1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid (Example 21a)), 0.19 g), and tetrakis(triphenylphosphine)palladium(0) (0.025 g) were added to a solution of 5-bromothiophene-2-sulfonic acid amide (0.242 g) in ethanol (2 ml). The mixture was heated at 90 C. for 2 hours. The mixture was cooled to room temperature and the solvents were evaporated under reduced pressure. The reaction mixture was triturated with acetone (10 ml) and filtered through a short silica gel column. The column was eluted with acetone and the resulting filtrate evaporated to give the title compound as a solid (0.064 g). m.p. 184-186 C. MS (APCI) 419 (M+H)+ 1 H NMR (DMSO) 8.44 (1H, s); 8.38 (1H, d); 7.67-7.58(5H, m); 7.49 (1H, d); 7.36 (1H, d); 7.29 (1H, dd); 6.98 (2H, d); 5.01 (1H, d); 4.35 (1H, p); 3.58-52 (1H, m); 2.85-2.73(1H, m); 2.69-2.59 (1H, m); 1.86-1.80 (1H, m); 1.69-1.61 (1H, m); 1.23 (3H, d).

References: [1]Patent: US6143751,2000,A .

27
[ 53595-65-6 ]
(2R)-4-[2-(tert-butyldimethylsilanyloxy)-4-pyridin-3-ylbutan-2-thioxy]benzeneboronic acid [ No CAS ]
[ 497-19-8 ]
(2R)-5(4-(2-Hydroxy-4-pyridin-3-yl-butanthio)phenyl)thiophene-2-sulfonic acid amide hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride;tetrakis(triphenylphosphine)palladium (0); In methanol; ethanol; dichloromethane; acetone;	d (2R)-5(4-(2-Hydroxy-4-pyridin-3-yl-butanthio)phenyl)thiophene-2-sulfonic acid amide hydrochloride 2M Aqueous sodium carbonate (0.24 ml), (2R)-4-[2-(tert-butyldimethylsilanyloxy)-4-pyridin-3-ylbutan-2-thioxy]benzeneboronic acid (Example 41c), 0.10 g), and tetrakis(triphenylphosphine)palladium(0) (0.01 g) were added to a solution of 5-bromothiophene-2-sulfonic acid amide (0.087 g) in ethanol (3 ml). The mixture was heated at 90 C. for 4 hours. The mixture was cooled to room temperature and solvents were evaporated under reduced pressure. The reaction mixture was triturated with acetone (10 ml) and filtered through a short silica gel column. The column was eluted with a further 10 ml of acetone. The filtrate was evaporated before purification by normal-phase HPLC, eluding with a gradient of 0-10% ethanol in dichloromethane. The colourless oil obtained was dissolved in methanol (3 ml), concentrated hydrochloric acid (0.2 ml) was added and the solution stirred at room temperature for 2 hours. The mixture was diluted with ether (10 ml) and the product was filtered off to give the title compound as a solid (0.075 g). m.p. 208-211 C. MS (APCI) 421 ((M-HCl)+H)+ 1 H NMR (DMSO) 8.76(1H, d); 8.70(1H, d); 8.33 (1H, d); 7.87 (1H, dd); 7.73 (2H, s); 7.62 (2H, d); 7.51 (2H, dd); 7.38 (2H, d); 3.65-3.60 (1H, m); 3.08 (2H, d); 2.99-2.84 (2H, m); 1.98-1.93 (1H, m); 1.82-1.73 (1H, m).

References: [1]Patent: US6143751,2000,A .

28
[ 53595-65-6 ]
[ 99768-12-4 ]
4-(5-Sulfamoyl-thiophen-2-yl)-benzoic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; ethanol; at 80 - 90℃; for 8 - 48h;	General Procedure A: Suzuki type coupling AA mixture of the aryl halide (1 eq,), the boronic acid or boronic ester (1.1-1.2 eq.), tetrakis (triphenylphosphine) palladium (0) (0.05-0.leq.), and 2M Na2C03 (2.2 eq.) in 0-20 %EtOH/ dioxane (degassed by vacuum, then N2 purge) is stirred 8-48 hours at 80-90 C.Reaction is allowed to cool, diluted with an organic solvent, eg. CH2CI2 or EtOAc,washed with aq. NaHC03 and brine, dried (Na2SC>4) and concentrated in vacuo. Thecrude mixture is purified by chromatography to give the desired product.; General Procedure C: Methyl Ester HydrolysisA mixture of the methyl ester and lithium hydroxide monohydrate is stirred in 10-25 %aqueous dioxane or 10-25 % aqueous tetrahydrofuran for 4-96 hours until the methylester is consumed. The reaction mixture is concentrated and dried in vacuo. Thecarboxylic acid lithium salt is used without further purification or is converted to thecarboxylic acid by adding H2O, washing with diethylether, adjusting the aqueous layerpH to ~ 2.0 with 1 N HC1, then filtering and drying the free acid in vacuo.; Intermediate Preparation 6 4-(5-Sulfamoyl-thiophen-2-yl)-benzoic acid, lithium saltThe title intermediate is prepared in a manner substantially analogous General Procedure A, followed by General Procedure C using of the 5-Bromo-thiophene-2-sulfonic acid amide (CAS 53595-65-6) and 4-methoxycarbonylphenyl boronic acid to give the desired intermediate. (180 mg,) MS (ES-) 282.0 (M-H)"

References: [1]Patent: WO2006/23462,2006,A1 .Location in patent: Page/Page column 46-47; 50-51.

29
[ 53595-65-6 ]
[ 39161-84-7 ]
[ 63032-09-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In N-methyl-acetamide; water;	Step A: Preparation of 5-(4-carboxymethylphenylthio)thiophene-2-sulfonamide 4-Mercaptophenylacetic acid (2.3 g) was dissolved in dimethylformamide under a nitrogen atmosphere and 1.8 g of potassium hydroxide dissolved in a minimum amount of water was added. 5-bromothiophene-2-sulfonamide (3.3 g) dissolved in dimethylformamide was added and the mixture heated at 120 C. for 2 hours. After cooling to room temperature water was added to the reaction mixture, the pH was adjusted to 8.6 and the mixture was extracted with ethyl acetate. The aqueous phase was separated and acidified, causing a solid to precipitate. The solid was collected by filtration and dried under vacuum to a weight of 3.25 g.
	With potassium hydroxide; In N-methyl-acetamide; water;	Step A: Preparation of 5-(4-carboxymethylphenylthio)thiophene-2-sulfonamide 4-Mercaptophenylacetic acid (2.3 g) was dissolved in dimethylformamide under a nitrogen atmosphere and 1.8 g of potassium hydroxide dissolved in a minimum amount of water was added. 5-bromothiophene-2-sulfonamide (3.3 g) dissolved in dimethylformamide was added and the mixture heated at 120C for 2 hours. After cooling to room temperature water was added to the reaction mixture, the pH was adjusted to 8.6 and the mixture was extracted with ethyl acetate. The aqueous phase was separated and acidified, causing a solid to precipitate. The solid was collected by filtration and dried under vacuum to a weight of 3.25 g.

References: [1]Patent: US4847289,1989,A .
[2]Patent: EP295049,1991,B1 .

30
[ 53595-65-6 ]
[ 6163-58-2 ]
[ 10473-14-0 ]
5-(2-methyl-3-oxobutyl)-thiophene-2-sulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
4.1%	With sodium hydrogencarbonate;palladium diacetate; In 1-methyl-pyrrolidin-2-one;	Preparation 10 5-(2-methyl-3-oxobutyl)-thiophene-2-sulfonamide 5-bromothiophene-2-sulfonamide (5.2 g, 21.5 mmol) and 3-methyl-3-buten-2-ol (2.8 g, 32.2 mmol) were dissolved in N-methylpyrrolidinone (40 mL) and treated with catalytic palladium diacetate (96 mg, 0.43 mmol), tris-(o-tolyl)-phosphine (262 mg, 0.86 mmol), and NaHCO3(2.2 g, 25.8 mmol). The mixture was stirred at 160C for 48 hours. TLC indicated the reaction was ca. 50% completed at that time. The solution was cooled to ambient temperature and partitioned between H2O/ethyl acetate, dried (MgSO4) and concentrated in vacuoto a dark brown oil. The residue was applied to a silica chromatography column and eluted with 2:3 hexane/ethyl acetate to yield 220 mg of a pale brown oil (4.1%).

References: [1]Patent: EP764632,1997,A2 .

31
[ 53595-65-6 ]
[ 879487-60-2 ]
[ 879487-61-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium phosphate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; water; at 90℃; for 4h;	(143f) 5-[2-Fluoro-5-(3-(6-methylpyridin-2-yl)-1-[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazol-4-yl)phenyl]thiophene-2-sulfonamide 2-(4-[4-Fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazol-3-yl)-6-methylpyridine (0.37 g, 0.70 mmol) obtained in Example (143d) and 5-bromothiophene-2-sulfonamide (0.19 g, 0.77 mmol) obtained in Example (143e) were dissolved in 1,2-dimethoxyethane (8 mL), and water (3 mL), tripotassium phosphate n-hydrate (0.30 g, 1.4 mmol), and dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II)-methylene chloride complex (0.057 g, 0.070 mmol) were added thereto. The resulting mixture was stirred under a nitrogen atmosphere at 90C for 4 hr. The reaction solution was cooled to room temperature, and water was added thereto. After extraction with ethyl acetate, the organic layer was washed with water and brine, and then dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (Biotage, eluding solvent: hexane/ethyl acetate) to obtain 0.36 g (yield: 95%) of the title compound as a light yellow solid. 1H-NMR (400 MHz, CDCl3) δ ppm: 7.74 (1H, s), 7.65 (1H, m), 7.60-7.56 (2H, m), 7.40 (1H, d, J = 7.8 Hz), 7.34 (1H, m), 7.27 (1H, m), 7.13-7.08 (2H, m), 5.53 (2H, s), 5.21 (2H, s), 3.71 (2H, t, J = 7.8 Hz), 2.50 (3H, s), 1.25 (9H, s), 0.97 (2H, t, J = 7.8 Hz), 0.00 (9H, s). MS(ESI) m/z: 545 (M+H)+

References: [1]Patent: EP1798229,2007,A1 .Location in patent: Page/Page column 144.

32
[ 53595-65-6 ]
[ 89-75-8 ]
[ 519055-62-0 ]

References: [1]Organic Process Research and Development,2009,vol. 13,p. 255 - 262.
[2]Organic Letters,2018,vol. 20,p. 6302 - 6305.

33
[ 53595-65-6 ]
[ 1272674-69-7 ]
[ 1272672-96-4 ]

Yield	Reaction Conditions	Operation in experiment
34.1%	With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 120℃; for 0.25h;microwave reactor;	Ethyl 5-chloro-3-[(cyanoacetyl)amino]-1-[4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2- yl)phenyl]-1 H-pyrrole-2-carboxylate (Intermediate 76) (150 mg, 0.328 mmol), 5- bromo-2-thiophenesulfonamide (159 mg, 0.655 mmol), cesium carbonate (320 mg, 0.983 mmol) and Pd(PPh3)4 (3.79 mg, 3.28 μηηοΙ) were mixed in a sealed tube with 1 ,4-dioxane (4 ml_), water (1 ml_). The reaction vessel was sealed and heated in a microwave reactor to 120 C for (3x5 min). The reaction mixture was then filtered and the resulting solid was triturated successively in 1 N HCI and CH3CN to give 5-[4-(2- chloro-6-cyano-7-hydroxy-5-oxo-4,5-dihydro-1 H-pyrrolo[3,2-b]pyridin-1 -yl)phenyl]-2- thiophenesulfonamide (50 mg, 0.1 12 mmol, 34.1 % yield) as a cream powder. HRMS: calculated for C18H10CIN4O4S2 (M-H)" : 444.9832; found: 444.9839. Rt: 2.03 min.

References: [1]Patent: WO2011/29855,2011,A1 .Location in patent: Page/Page column 142.

34
[ 53595-65-6 ]
[ 33513-42-7 ]
[ 104438-09-7 ]

References: [1]Organic Letters,2011,vol. 13,p. 6152 - 6155.
[2]Organic and Biomolecular Chemistry,2013,vol. 11,p. 2460 - 2465.

35
[ 53595-65-6 ]
[ 99769-19-4 ]
[ 1176724-02-9 ]

Yield	Reaction Conditions	Operation in experiment
53%	With potassium phosphate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; N,N-dimethyl-formamide; at 85℃;Inert atmosphere;	(1) 1,1'-Bis(diphenylphosphino)ferrocene-palladium(II) dichloride-dichloromethane complex (272 mg, 0.33 mmol), 3-methoxycarbonylphenylboronic acid (898 mg, 4.99 mmol), and tripotassium phosphate (1.41 g, 6.64 mmol) were added to a solution of commercially available 5-bromothiophene-2-sulfonamide (805 mg, 3.33 mmol) in mixture of 1,4-dioxane (10 mL) and DMF (1 mL), followed by stirring at 85C overnight in an argon atmosphere. The reaction solution was concentrated. A saturated aqueous solution of sodium chloride was added to the residue, followed by extraction with methylene chloride and drying over anhydrous sodium sulfate. The solvent was distilled off, and methanol was added to the residue. The precipitated solid was filtered off. The residue obtained by distilling the solvent off was subjected to purification by silica gel column chromatography to obtain 3-(5-sulfamoyl-2-thienyl)benzoic acid methyl ester (529 mg, 1.78 mmol) (yield: 53%). ES-MS (m/z): 296 (M-H)-.

References: [1]Patent: EP2520575,2012,A1 .Location in patent: Page/Page column 68.

36
[ 871231-45-7 ]
[ 53595-65-6 ]
[ 1620108-50-0 ]

References: [1]Journal of Organic Chemistry,2014,vol. 79,p. 7243 - 7249.

Historical Records

Technical Information

• Alkyl Halide Occurrence • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Chan-Lam Coupling Reaction • General Reactivity • Grignard Reaction • Hiyama Cross-Coupling Reaction • Hydride Reductions • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Leuckart-Wallach Reaction • Mannich Reaction • Petasis Reaction • Preparation of Amines • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Dihalides • Specialized Acylation Reagents-Vilsmeier Reagent • Stille Coupling • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Ugi Reaction

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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

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

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CAS No.: 53595-65-6

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CAS No.: 53595-65-6

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