24065-33-6

Basic information

• Product Name: 5-CHLOROTHIOPHENE-2-CARBOXYLIC ACID
• Synonyms: 5-CHLOROTHIOPHENE-2-CARBOXYLIC ACID;5-CHLORO-2-THIOPHENECARBOXYLIC ACID;AKOS B000092;2-Thiophenecarboxylic acid, 5-chloro-;5-chloro-2-thiophenecarboxylicaci;TIMTEC-BB SBB003937;RARECHEM AL BE 0303;5-Chlorothiophene-2-carboxylicacid,98%
• CAS NO: 24065-33-6
• Molecular Formula: C₅H₃ClO₂S
• Molecular Weight: 162.59
• EINECS: -0
• Product Categories: Thiophene&Benzothiophene;Miscellaneous;Halogenated Heterocycles;Heterocyclic Building Blocks;Thiophenes;ThiophenesBuilding Blocks;Heterocycles;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Sulfur & Selenium Compounds;Intermediates;Heterocycle-oher series;Intermediate of Rivaroxaban
• Mol File: 24065-33-6.mol
• Article Data: 18

Chemical Properties

• Melting Point: 154-158 °C(lit.)
• Boiling Point: 287 °C at 760 mmHg
• Flash Point: 127.4 °C
• Appearance: Cream-yellow/Powder
• Density: 1.466 (estimate)
• Vapor Pressure: 0.00119mmHg at 25°C
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 3.32±0.10(Predicted)
• BRN: 118361
• CAS DataBase Reference: 5-CHLOROTHIOPHENE-2-CARBOXYLIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: 5-CHLOROTHIOPHENE-2-CARBOXYLIC ACID(24065-33-6)
• EPA Substance Registry System: 5-CHLOROTHIOPHENE-2-CARBOXYLIC ACID(24065-33-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36-43-36/37/38
• Safety Statements: 26-36-37/39
• WGK Germany: 3
• RTECS: XM8400000
• HazardClass: IRRITANT
• Hazardous Substances Data: 24065-33-6(Hazardous Substances Data)

Usage

Chemical Properties

White to light yellow crystal powder

Uses

Different sources of media describe the Uses of 24065-33-6 differently. You can refer to the following data:
1. A metabolite of Rivaroxaban (R538000).
2. 5-Chlorothiophene-2-carboxylic acid can be used in the synthesis of the following:rivaroxaban, an oxazolidinone derivative used in the treatment of thromboembolic disorders5-chloro-4-nitrothiophene-2-carboxylic acid, which can be used in the synthesis of thieno[2,3-b][1,4]thiapezine-5-ones

InChI:InChI=1/C5H3ClO2S/c6-4-2-1-3(9-4)5(7)8/h1-2H,(H,7,8)/p-1

Synthetic route

5-Chloro-2-thiophenecarboxaldehyde (7283-96-7) → 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

Conditions	Yield
Stage #1: 5-Chloro-2-thiophenecarboxaldehyde With sodium hydroxide at -5 - 0℃; for 2h; Large scale; Stage #2: With chlorine at 15 - 30℃; for 8h; Large scale;	98.8%
With tert.-butylhydroperoxide In dichloromethane at 35 - 40℃; for 4h; Reagent/catalyst; Temperature;	96%
With 1,4-dithio-D,L-threitol; recombinant aldehyde dehydrogenase from bovine lens; water‐forming NADH oxidase from Streptococcus mutans; NAD In aq. phosphate buffer at 40℃; for 4h; pH=8.5; Reagent/catalyst; Green chemistry; Enzymatic reaction; chemoselective reaction;

5-bromo-2-chlorothiophene (2873-18-9) + carbon dioxide (124-38-9) → 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

Conditions	Yield
Stage #1: 5-bromo-2-chlorothiophene With iodine; magnesium In tetrahydrofuran at 22 - 28℃; Inert atmosphere; Stage #2: carbon dioxide With hydrogenchloride In water at -15℃; for 1.5h;	96.7%
Multistep reaction;

5-chloro-2-trichloroacetylthiophene → 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

Conditions	Yield
With N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide In toluene at 20℃; for 2h; Reagent/catalyst; Solvent;	95%

2-acetyl-5-chlorothiophene (6310-09-4) → 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

Conditions	Yield
With sodium chlorite; potassium dihydrogenphosphate In water; acetone at 0 - 30℃; for 22h;	84.9%
With bromine; sodium hydroxide In 1,4-dioxane; water at 0 - 20℃;	76.1%
With sodium hydroxide; potassium permanganate; water

2-thiophenylcarboxylic acid (527-72-0) → 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

Conditions	Yield
With trichloroisocyanuric acid; sulfuric acid at -5 - 5℃; for 4h; Reagent/catalyst; Temperature;	82.2%
With chlorine; acetic acid

2-thienyl chloride (96-43-5) + carbon dioxide (124-38-9) → 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

Conditions	Yield
Stage #1: 2-thienyl chloride With lithium diisopropyl amide In tetrahydrofuran at 20℃; for 0.000833333h; Flow reactor; Stage #2: carbon dioxide In tetrahydrofuran at 20℃; for 0.000138889h; Flow reactor; Stage #3: With water; acetic acid In tetrahydrofuran at 20℃; under 7500.75 Torr; Flow reactor;	77%
With ethylaluminum dichloride In hexane; chlorobenzene at 100℃; under 22502.3 Torr; for 3h; Autoclave; Inert atmosphere; regioselective reaction;	41%
Stage #1: 2-thienyl chloride With n-butyllithium In tetrahydrofuran; hexane at 0℃; Stage #2: carbon dioxide In tetrahydrofuran; hexane Stage #3: With hydrogenchloride In tetrahydrofuran; hexane; water at 0℃;	> 70 %Chromat.

2-thienyl chloride (96-43-5) → 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

Conditions	Yield
With palladium diacetate; sodium persulfate In acetic acid for 7h; Heating;	19.6%
With n-butyllithium; diethyl ether anschliessend Behandeln mit festem Kohlendioxid;

ethyl acetoacetate (141-97-9) + (5-chlorothiophen-2-yl)boronic acid → 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

Conditions	Yield
With copper(l) iodide; potassium carbonate In dimethyl sulfoxide at 100℃; for 24h; Inert atmosphere;	3%

2-thienyl chloride (96-43-5) + diethyl ether (60-29-7) → 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

Conditions	Yield
With sodium amalgam Behandeln der Reaktionsloesung mit festem Kohlendioxid;
With sodium Behandeln der Reaktionsloesung mit festem Kohlendioxid;

2,5-diclorothiophene (3172-52-9) → 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

Conditions	Yield
With n-butyllithium; diethyl ether anschliessend Behandeln mit festem Kohlendioxid;

2-thiophenylcarboxylic acid (527-72-0) → 2,5-diclorothiophene (3172-52-9) + 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

Conditions	Yield
With alkaline aqueous sodium hypochlorite solution anschliessend Erwaermen mit wss. Salzsaeure;

5-chlorothiophene-2-carbonyl chloride (42518-98-9) → 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

Conditions	Yield
With sodium hydroxide

5-chloro-2-thiophenecarboxylic acid N-methylamide (97799-98-9) → 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

Conditions	Yield
With water

5-chloro-[2]thienyl sodium + diethyl ether (60-29-7) + carbon dioxide (124-38-9) → 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

2-thiophenylcarboxylic acid (527-72-0) + water (7732-18-5) + chlorine (7782-50-5) + acetic acid (64-19-7) → 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

2-thiophenylcarboxylic acid (527-72-0) + aqueous sodium hypochlorite → 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

Conditions	Yield
und anschl. mit wss. HCl;

5-chloro-2-acetylthiophene oxime (42520-87-6) → 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / sodium hydroxide / acetone; H2O 2: 35 percent / anhydrous sodium acetate / H2O; methanol / 60 - 70 °C 3: water View Scheme

5-chloro-2-acetylthiophene oxime benzenesulfonate (97799-96-7) → 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 35 percent / anhydrous sodium acetate / H2O; methanol / 60 - 70 °C 2: water View Scheme

5-Chlorothiophene-2-carboxylic acid (24065-33-6) → 5-chlorothiophene-2-carbonyl chloride (42518-98-9)

Conditions	Yield
With thionyl chloride; N,N-dimethyl-formamide In dichloromethane for 16h; Heating / reflux;	100%
With oxalyl dichloride In dichloromethane for 16h; Reflux;	100%
With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 40℃; for 4h; Solvent; Reagent/catalyst; Temperature;	100%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + benzyl 3-amino-tetrahydro-furan-3-carboxylate (1037301-02-2) → 3-[(5-chloro-thiophen-2-yl)-carbonylamino]-tetrahydro-furan-3-carboxylic acid benzyl ester (919098-95-6)

Conditions	Yield
With 4-methyl-morpholine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In N,N-dimethyl-formamide at 20℃; for 20h; Product distribution / selectivity;	100%
With 4-methyl-morpholine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In N,N-dimethyl-formamide at 20℃; for 20h;	100%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) → 4-bromo-5-chlorothiophene-2-carboxylic acid (60729-37-5)

Conditions	Yield
With iron(III) chloride; bromine In acetic acid at 25℃; for 168h; Heating / reflux;	100%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + methyl 2-(aminomethyl)benzoate hydrochloride salt (849020-92-4) → methyl 2-{[(5-chlorothiophen-2-yl)carbonylamino]methyl}benzoate (1057653-07-2)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 28h;	100%

methanol (67-56-1) + 5-Chlorothiophene-2-carboxylic acid (24065-33-6) → methyl 5-chloro-2-thiophenecarboxylate (35475-03-7)

Conditions	Yield
With sulfuric acid at 50 - 55℃; for 12 - 20h;	99%
With sulfuric acid at 50℃; for 20h;	95%
With hydrogenchloride at 60℃; for 16h;	94.1%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + 4-isopropyl-1-methylcyclohex-3-en-1-amine → 5-chloro-N-(4-isopropyl-1-methylcyclohex-3-en-1-yl)thiophene-2-carboxamide

Conditions	Yield
Stage #1: 5-Chlorothiophene-2-carboxylic acid With thionyl chloride; N,N-dimethyl-formamide In dichloromethane Reflux; Stage #2: 4-isopropyl-1-methylcyclohex-3-en-1-amine With triethylamine In dichloromethane; N,N-dimethyl-formamide Reflux;	98.87%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + tert-butyl D-alaninate (16367-69-4, 21691-50-9, 59624-87-2) → (R)-2-[(5-chloro-thiophene-2-carbonyl)-amino]-propionic acid tert-butyl ester (869859-84-7)

Conditions	Yield
With 4-methyl-morpholine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In tetrahydrofuran at 20℃; for 2h;	98%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + (bromomethylcyclohexane) (2550-36-9) → cyclohexyl-methyl 5-chlorothiophene-2-carboxylate (1448433-72-4)

Conditions	Yield
With potassium carbonate at 85℃; for 72h; Inert atmosphere;	97%
With potassium carbonate at 85℃; for 72h; Inert atmosphere;	97%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + 4-{4-[(5S)-5-(amino methyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one hydrochloride (898543-06-1) → Rivaroxaban (366789-02-8)

Conditions	Yield
Stage #1: 5-Chlorothiophene-2-carboxylic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 25℃; for 0.5h; Stage #2: 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholin-3-one hydrochloride In N,N-dimethyl-formamide at 34℃; for 4h;	96.3%
With 4-methyl-morpholine; 2-chloro-4,6-dimethoxy-1 ,3,5-triazine In N,N-dimethyl-formamide at 20℃; for 2.83333h; Reagent/catalyst; Cooling with ice;	95.2%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 24h; pH=8 - 9; Large scale;	94.7%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + (R)-amino-phenyl-acetic acid ethyl ester (39251-40-6) → (2R)-2-[(5-chloro-thiophene-2-carbonyl)-amino]-2 phenyl-acetic acid ethyl ester (869786-01-6)

Conditions	Yield
With 4-methyl-morpholine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In tetrahydrofuran at 20℃; for 2h;	96%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + (9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecan-3-yl)(1,2,3,4-tetrahydroisoquinolin-7-yl)methanone (1240015-37-5) → (5-chlorothiophen-2-yl)(7-(9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecan-3-carbonyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanone (1239951-93-9)

Conditions	Yield
Stage #1: 5-Chlorothiophene-2-carboxylic acid With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In tetrahydrofuran at 25℃; for 0.5h; Inert atmosphere; Stage #2: (9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecan-3-yl)(1,2,3,4-tetrahydroisoquinolin-7-yl)methanone With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 25℃; for 15h;	96%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + tert-butyl glycidyl ether (7580-85-0) → (2-(2-methyl-2-propoxy)-ethyl) 5-chlorothiophene-2-carboxylate (91505-31-6)

Conditions	Yield
Stage #1: 5-Chlorothiophene-2-carboxylic acid With oxalyl dichloride In 1,2-dichloro-ethane; N,N-dimethyl-formamide at 0 - 20℃; for 2h; Stage #2: tert-butyl glycidyl ether With triethylamine In tetrahydrofuran at 0 - 20℃; for 2h;	95.56%

4-[4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]morpholine-3-one (446292-10-0) + 5-Chlorothiophene-2-carboxylic acid (24065-33-6) → Rivaroxaban (366789-02-8)

Conditions	Yield
With 4-methyl-morpholine; hydrogenchloride In water; N,N-dimethyl-formamide at 20℃; for 2.83333h;	95.2%
With ortho-iodophenylboronic acid In dichloromethane at 30℃; for 48h; Reagent/catalyst; Time; Concentration; Temperature; Solvent; Dean-Stark;	85%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 3h;	68.9%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + tert-butyl trans-2-(aminomethyl)cyclohexylcarbamate → tert-butyl [(1RS,2SR)-2-({[(5-chlorothiophen-2-yl)carbonyl]amino}methyl)cyclohexyl]carbamate

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 20℃;	95%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + C15H21N3O4 (1082937-60-7) → C20H22ClN3O5S (1082937-62-9)

Conditions	Yield
With diisopropyl-carbodiimide; dmap In chloroform at 0 - 20℃;	94%
With dmap; diisopropyl-carbodiimide In chloroform at 0 - 20℃;	94%
With dmap; diisopropyl-carbodiimide In chloroform at 0 - 20℃;	94%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one hydrochloride → Rivaroxaban (366789-02-8)

Conditions	Yield
Stage #1: 5-Chlorothiophene-2-carboxylic acid; 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one hydrochloride With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine In ethyl acetate at 10 - 25℃; for 12.5h; Stage #2: With water In ethyl acetate for 1h;	94%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + 4-[5-(naphtho[2,1-b]furan-2-yl)-1,3,4-oxadiazol-2-yl]aniline → 5-chloro-N-(4-(5-(naphtho[2,1-b]furan-2-yl)-1,3,4-oxadiazol-2-yl)phenyl)thiophene-2-carboxamide

Conditions	Yield
Stage #1: 4-[5-(naphtho[2,1-b]furan-2-yl)-1,3,4-oxadiazol-2-yl]aniline With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; Inert atmosphere; Stage #2: 5-Chlorothiophene-2-carboxylic acid In dichloromethane at 20℃; Inert atmosphere;	94%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + tert-butyl 4-(1-amino-3-methylbutyl)piperidine-1-carboxylate → tert-butyl 4-(1-(5-chlorothiophene-2-carboxamido)-3-methylbutyl)piperidine-1-carboxylate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 3h;	94%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + (S)-5-(aminomethyl)-3-(4-iodophenyl)oxazolidin-2-one → (S)-5-chloro-N-((3-(4-iodophenyl)-2-oxooxazolidin-5-yl)methyl)thiophene-2-carboxamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 3h;	93.8%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + (3R,4S)-3-amino-4-[4-(2-oxo-2H-pyridin-1-yl)-benzoylamino]-pyrrolidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester trifluoroacetic acid salt (1364510-82-6) → (3R,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-[4-(2-oxo-2H-pyridin-1-yl)-benzoylamino]-pyrrolidine-1-carboxylic acid 9H-fluoren-9-yl methyl ester (766553-17-7)

Conditions	Yield
With 4-methyl-morpholine; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate In tetrahydrofuran at 20℃;	93%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + 6-(2'-Aminothiazol-4'-yl)-3,4-dihydrocarbostyril → 5-chloro-N-(4-(2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)thiazol-2-yl)thiophene-2-carboxamide

Conditions	Yield
With pyridine; propylphosphonic anhydride In ethyl acetate; acetonitrile at 100℃; Sealed tube;	93%

2-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-1H-isoindole-1,3(2H)-dione (446292-08-6) + 5-Chlorothiophene-2-carboxylic acid (24065-33-6) → Rivaroxaban (366789-02-8)

Conditions	Yield
Stage #1: 2-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-1H-isoindole-1,3(2H)-dione With methylamine In ethanol; water at 60℃; for 3h; Stage #2: 5-Chlorothiophene-2-carboxylic acid With 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride In ethanol; water at 25℃; for 12h; Solvent; Temperature;	92.8%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + (S)-4-(5-(aminomethyl)-2-oxooxazolidin-3-yl)benzonitrile (1082937-34-5) → (S)-5-chloro-N-((3-(4-cyanophenyl)-2-oxooxazolidin-5-yl)methyl)thiophene-2-carboxamide (1027385-05-2)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 20℃; for 12h;	91.2%
With 4-hydroxybenzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; for 15h;	82%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + dimethyl amine (124-40-3) → 5-chloro-N,N-dimethylthiophene-2-carboxamide

Conditions	Yield
Stage #1: 5-Chlorothiophene-2-carboxylic acid With thionyl chloride In N,N-dimethyl-formamide for 3h; Inert atmosphere; Reflux; Stage #2: dimethyl amine With triethylamine In diethyl ether; water at 0℃; for 1h; Inert atmosphere;	91%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + tert-butyl (S)-4-(1-amino-3-methylbutyl)piperidine-1-carboxylate → tert-butyl (S)-4-(1-(5-chlorothiophene-2-carboxamido)-3-methylbutyl)piperidine-1-carboxylate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃;	91%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) + tert-butyl (S)-4-(amino(cyclopropyl)methyl)piperidine-1-carboxylate → tert-butyl (S)-4-((5-chlorothiophene-2-carboxamido)(cyclopropyl)methyl)piperidine-1-carboxylate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃;	91%

5-Chlorothiophene-2-carboxylic acid (24065-33-6) → 2-thienyl chloride (96-43-5)

Conditions	Yield
With triethylsilane; palladium diacetate; 2,2-dimethylpropanoic anhydride; 1,4-di(diphenylphosphino)-butane In toluene at 160℃; for 15h; chemoselective reaction;	91%

Upstream product

• 96-43-5 2-thienyl chloride 
• 60-29-7 diethyl ether 
• 97799-98-9 5-chloro-2-thiophenecarboxylic acid N-methylamide 
• 7283-96-7 5-Chloro-2-thiophenecarboxaldehyde 
• 97799-96-7 5-chloro-2-acetylthiophene oxime benzenesulfonate 
• 3172-52-9 2,5-diclorothiophene 
• 141-97-9 ethyl acetoacetate 
• 162607-18-3 (5-chlorothiophen-2-yl)boronic acid 
• 124-38-9 carbon dioxide 
• 42520-87-6 5-chloro-2-acetylthiophene oxime 
• 527-72-0 2-thiophenylcarboxylic acid 
• 7732-18-5 water 
• 7782-50-5 chlorine 
• 64-19-7 acetic acid 

Downstream Products

• 35475-03-7 methyl 5-chloro-2-thiophenecarboxylate 
• 5751-82-6 ethyl 5‐chlorothiophene‐2‐carboxylate 
• 42518-98-9 5-chlorothiophene-2-carbonyl chloride 
• 811811-33-3 EMD 495235 

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BUMETANIDE DERIVATIVES FOR THE THERAPY OF HYPERHIDROSIS

The present invention relates to bumetanide derivatives of formula (I) as well as pharmaceutical compositions comprising these compounds for use in the treatment or prevention of diseases/disorders involving Na+- K+- 2CI- - cotransporters (NKCCs), and particularly for use in the treatment or prevention of hyperhidrosis.

Method for preparing 5-chlorothiophene-2-carboxylic acid through one-pot synthesis

The invention relates to a method for preparing 5-chlorothiophene-2-carboxylic acid through one-pot synthesis. The method comprises the following steps: leading or adding a chlorinated reagent into 2-thiophenecarboxaldehyde for heat insulation reaction, so as to obtain an intermediate 5-chlorine2-thiophenecarboxaldehyde after the reaction is completed, wherein the intermediate 5-chlorine2-thiophenecarboxaldehyde is directly used for the next reaction without separation; slowly dropping the intermediate 5-chlorine2-thiophenecarboxaldehyde into pre-cooled caustic soda liquid, controlling the reaction temperature to be not higher than 30 DEG C, cooling after the dropping is completed, slowly leading chlorine into the pre-cooled caustic soda liquid for heat insulation reaction after the leading of the chlorine is completed, cooling to 5 DEG C after a center control reaction is completed, adding sodium sulfite for quenching, adding a solvent for extraction and impurities elimination, regulating the pH value of a water phase with concentrated hydrochloric acid, performing suction filtration, recrystallizing a filter cake, and drying, so as to obtain an target compound. According to the method, the defects of the prior art of being high in raw materials, complex in operation and more in three wastes are overcome; the provided method for synthesizing 5-chlorothiophene-2-carboxylic acidis suitable for industrial production.