10177-29-4

Basic information

• Product Name: 4-Chloronicotinic acid
• Synonyms: 4-CHLOROPYRIDINE-3-CARBOXYLIC ACID;4-CHLORO-3-PYRIDINECARBOXYLIC ACID;4-CHLORONICOTINIC ACID;IFLAB-BB F1926-0029;4-Chloro-3-pyridinecarboxylic;4-CHLORONICOTINIC ACID,99%;4-Choronicotinic acid;4-Chloronicotinic acid ,97%
• CAS NO: 10177-29-4
• Molecular Formula: C₆H₄ClNO₂
• Molecular Weight: 157.55
• EINECS: -0
• Product Categories: blocks;Carboxes;Pyridines;Pyridine;Pyridines, Pyrimidines, Purines and Pteredines;pharmacetical;Pyridine series;Carboxylic Acids;CHIRAL CHEMICALS;Carboxylic Acids
• Mol File: 10177-29-4.mol
• Article Data: 15

Chemical Properties

• Melting Point: 139-143 °C
• Boiling Point: 301.9 °C at 760 mmHg
• Flash Point: 136.4 °C
• Appearance: yellow powder
• Density: 1.47 g/cm³
• Vapor Pressure: 0.000454mmHg at 25°C
• Refractive Index: 1.59
• Storage Temp.: Keep Cold
• Solubility: Soluble in organic solvents at 20 deg C
• PKA: 0.78±0.25(Predicted)
• BRN: 9255849
• CAS DataBase Reference: 4-Chloronicotinic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Chloronicotinic acid(10177-29-4)
• EPA Substance Registry System: 4-Chloronicotinic acid(10177-29-4)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• HazardClass: IRRITANT, KEEP COLD
• PackingGroup: III
• Hazardous Substances Data: 10177-29-4(Hazardous Substances Data)

Usage

Chemical Properties

White to light brown solid

Uses

Different sources of media describe the Uses of 10177-29-4 differently. You can refer to the following data:
1. 4-Chloronicotinic Acid is a building block used in a synthesis of benzocanthinones via tributyltin hydride radical induced cyclization. It is also used in a synthesis of heterocyclic analogues of xanthone.
2. Building block used in a synthesis of benzocanthinones via tributyltin hydride radical induced cyclization. Also used in a synthesis of heterocyclic analogues of xanthone.

InChI:InChI=1/C6H4ClNO2/c7-5-1-2-8-3-4(5)6(9)10/h1-3H,(H,9,10)

Synthetic route

4-Chloropyridine (626-61-9) + carbon dioxide (124-38-9) → 4-chloronicotinic acid (10177-29-4)

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran 1.) -78 deg C, 20 min, 2.) 18 h;	96%
Stage #1: 4-Chloropyridine With lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; Inert atmosphere; Stage #2: carbon dioxide In tetrahydrofuran; hexane	80%
Stage #1: 4-Chloropyridine With lithium diisopropyl amide In tetrahydrofuran; hexanes at -78℃; Inert atmosphere; Stage #2: carbon dioxide In tetrahydrofuran; hexanes
Stage #1: 4-Chloropyridine With lithium diisopropyl amide In tetrahydrofuran at -78℃; Stage #2: carbon dioxide In tetrahydrofuran at -78 - 20℃; Product distribution / selectivity;
Stage #1: 4-Chloropyridine With lithium diisopropyl amide In tetrahydrofuran at -78℃; Stage #2: carbon dioxide In tetrahydrofuran at -78℃;

lithium; 4-chloro-nicotinate → 4-chloronicotinic acid (10177-29-4)

Conditions	Yield
With Amberlyst(R) IR-200 In methanol at 20℃; for 0.25h;	75%

4-chloro-3-methylpyridine (1681-36-3) → 4-chloronicotinic acid (10177-29-4)

Conditions	Yield
With potassium permanganate In water at 80 - 90℃; for 4h;	65%

carbon dioxide (124-38-9) → 4-chloronicotinic acid (10177-29-4)

Conditions	Yield
Stage #1: 4-Chloropyridine With lithium diisopropyl amide In tetrahydrofuran; hexanes at -78℃; for 1h; Stage #2: carbon dioxide In tetrahydrofuran; hexanes at -78 - 20℃;	61%
Stage #1: 4-Chloropyridine With lithium diisopropyl amide In tetrahydrofuran; hexanes at -78℃; for 1h; Stage #2: carbon dioxide In tetrahydrofuran; hexanes	61%

carbon dioxide (124-38-9) + 4-chlorpyridine hydrochloride (7379-35-3) → 4-chloronicotinic acid (10177-29-4)

Conditions	Yield
Stage #1: 4-chlorpyridine hydrochloride With sodium carbonate In water Stage #2: With n-butyllithium; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #3: carbon dioxide In tetrahydrofuran at 20℃; for 12h; Inert atmosphere;	57%

4-chloronicotinaldehyde (114077-82-6) → 4-chloronicotinic acid (10177-29-4)

Conditions	Yield
With potassium permanganate In water for 3h; Heating / reflux;	56%
With potassium permanganate In water; acetonitrile

4-hydroxynicotinic acid (609-70-1) → 4-chloronicotinic acid (10177-29-4)

Conditions	Yield
With thionyl chloride anschliessende Hydrolyse;

Nicotinic acid N-oxide (2398-81-4) + phosphorus pentachloride (10026-13-8, 874483-75-7) + trichlorophosphate (10025-87-3, 12599-09-6, 63736-95-8) → 2-chloronicotinic acid (2942-59-8) + 4-chloronicotinic acid (10177-29-4)

nicotinic acid-1-oxide → 2-chloronicotinic acid (2942-59-8) + 4-chloronicotinic acid (10177-29-4)

Conditions	Yield
With phosphorus pentachloride; trichlorophosphate

nicotinic acid (59-67-6) + potassium → 4-chloronicotinic acid (10177-29-4) + Nα-Fmoc-Nim-tert-butyloxycarbonyl-L-tryptophan 4-hydroxymethylphenoxy resin

Conditions	Yield
Multi-step reaction with 2 steps 1.1: BuLi; 2,2,6,6-tetramethylpiperidine / tetrahydrofuran; hexane / 0.67 h / -75 - -55 °C 1.2: 79 percent / hexachloroethane / tetrahydrofuran; hexane / -55 - 20 °C 2.1: 75 percent / Amberlyst(R) IR-200 / methanol / 0.25 h / 20 °C View Scheme

3-picoline-N-oxide (1003-73-2) → 4-chloronicotinic acid (10177-29-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 51 percent / HNO3, H2SO4 / 2 h 2: 97 percent / HCl, PCl3 / CHCl3 / 0.33 h / Heating 3: 65 percent / KMnO4 / H2O / 4 h / 80 - 90 °C View Scheme

3-methyl-4-nitropyridine N-oxide (1074-98-2) → 4-chloronicotinic acid (10177-29-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 97 percent / HCl, PCl3 / CHCl3 / 0.33 h / Heating 2: 65 percent / KMnO4 / H2O / 4 h / 80 - 90 °C View Scheme

nicotinic acid (59-67-6) → 4-chloronicotinic acid (10177-29-4)

Conditions	Yield
Stage #1: nicotinic acid With n-butyllithium; 2,2,6,6-tetramethylpiperidinyl-lithium In tetrahydrofuran at -78℃; Stage #2: With hexachloroethane In tetrahydrofuran at -78 - 20℃; Product distribution / selectivity;

4-chlorpyridine hydrochloride (7379-35-3) → 4-chloronicotinic acid (10177-29-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide 2: lithium diisopropyl amide / hexane; tetrahydrofuran / -78 °C / Inert atmosphere View Scheme

2,5-dichlorbenzenethiol (5858-18-4) + 4-chloronicotinic acid (10177-29-4) → C12H7Cl2NO2S*ClH

Conditions	Yield
In acetone for 3h; Heating / reflux;	100%

4-chloronicotinic acid (10177-29-4) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → methyl 4-chloronicotinate (63592-85-8)

Conditions	Yield
With oxalyl dichloride In dichloromethane at 20℃; for 3h; Inert atmosphere;	99.16%

4-chloronicotinic acid (10177-29-4) → 4-chloronicotinoyl chloride (100791-00-2)

Conditions	Yield
With thionyl chloride at 80℃; for 1.5h;	98.5%
With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 3h;
With thionyl chloride for 1.5h; Reflux;

methanol (67-56-1) + 4-chloronicotinic acid (10177-29-4) → methyl 4-chloronicotinate (63592-85-8)

Conditions	Yield
Stage #1: 4-chloronicotinic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 0.75h; Stage #2: methanol In dichloromethane at 0℃;	98%
Stage #1: 4-chloronicotinic acid With thionyl chloride Reflux; Stage #2: methanol In dichloromethane at 0℃; Alkaline conditions;	83%
Stage #1: 4-chloronicotinic acid With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 3h; Stage #2: methanol In dichloromethane; N,N-dimethyl-formamide for 0.5h;	50%
Stage #1: 4-chloronicotinic acid With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 2h; Stage #2: methanol In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 0.5h;
Stage #1: 4-chloronicotinic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 2h; Stage #2: methanol In dichloromethane at 0 - 20℃; for 0.5h;

5-chloro-2-methylthiophenol (18858-06-5) + 4-chloronicotinic acid (10177-29-4) → 4-[(2-methyl-5-chlorophenyl)thio]pyridine-3-carboxylic acid hydrochloride

Conditions	Yield
In acetone for 3h; Substitution; Heating;	95%

4-chloronicotinic acid (10177-29-4) + benzyl alcohol (100-51-6) → benzyl-4-chloropyridin-3-yl carbamate (1033418-69-7)

Conditions	Yield
With diphenyl phosphoryl azide; triethylamine In acetonitrile at 120℃;	95%

ethanol (64-17-5) + 4-chloronicotinic acid (10177-29-4) → ethyl 4-chloronicotinate (37831-62-2)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 0℃; for 4h;	94%
Stage #1: 4-chloronicotinic acid With thionyl chloride for 1.5h; Heating / reflux; Stage #2: ethanol With N-ethyl-N,N-diisopropylamine In ethanol at 0 - 20℃; for 4h;	94%
Stage #1: 4-chloronicotinic acid With thionyl chloride at 80℃; for 1.5h; Stage #2: ethanol With N-ethyl-N,N-diisopropylamine at 0 - 20℃; for 4h;	74.7%

2-nitro-5-chlorothiophenol (14371-79-0) + 4-chloronicotinic acid (10177-29-4) → 4-(2-nitro-5-chlorothiophenoxy)pyridine-3-carboxylic acid hydrochloride

Conditions	Yield
In acetone for 1h; Heating;	92%

3-chlorophenylthiol (2037-31-2) + 4-chloronicotinic acid (10177-29-4) → C12H8ClNO2S*ClH

Conditions	Yield
In acetone for 3h; Heating / reflux; Under N2;	91%

N-(3,4,5-trimethoxybenzyl)cyclopropanamine (14471-17-1) + 4-chloronicotinic acid (10177-29-4) → 4-chloro-N-cyclopropyl-N-(3,4,5-trimethoxybenzyl)nicotinamide

Conditions	Yield
Stage #1: 4-chloronicotinic acid With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 1.5h; Stage #2: N-(3,4,5-trimethoxybenzyl)cyclopropanamine With triethylamine In dichloromethane at 0℃; for 1h;	91%

4-chloronicotinic acid (10177-29-4) + methyl 2,3-deoxy-3-(azido)-4,6-O-isopropylidene-β-D-glucosamine (334002-51-6) → N-((4aR,6R,7R,8R,8aS)-8-Azido-6-methoxy-2,2-dimethyl-hexahydro-pyrano[3,2-d][1,3]dioxin-7-yl)-4-chloro-nicotinamide (334002-76-5)

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃;	89%
With dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃;	33%

2-bromo-5-fluorobenzene-1-thiol (55389-14-5) + 4-chloronicotinic acid (10177-29-4) → C12H7BrFNO2S*ClH

Conditions	Yield
In acetone for 3h; Heating / reflux; Under N2;	87%

2-isopropyliodobenzene (19099-54-8) + 4-chloronicotinic acid (10177-29-4) + bicyclo[2.2.1]hepta-2,5-diene (121-46-0) → 7-isopropylbenzo[f]isoquinoline

Conditions	Yield
With palladium diacetate; caesium carbonate; tricyclohexylphosphine In 1,4-dioxane at 130℃; for 18h; Schlenk technique; Sealed tube; Inert atmosphere;	86%

4-((2-methyl-6-(trifluoromethyl)pyrimidin-4-yl)oxy)aniline + 4-chloronicotinic acid (10177-29-4) → 4-chloro-N-(4-((2-methyl-6-(trifluoromethyl)pyrimidin-4yl)oxy)phenyl)nicotinamide

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;	85.2%

diazomethane (186581-53-3, 908094-01-9) + 4-chloronicotinic acid (10177-29-4) → methyl 4-chloronicotinate (63592-85-8)

Conditions	Yield
	85%

4-chloronicotinic acid (10177-29-4) + phenylacetonitrile (140-29-4) → 4-[α-cyano(phenyl)methyl]nicotinic acid (1345044-42-9)

Conditions	Yield
Stage #1: 4-chloronicotinic acid; phenylacetonitrile With potassium tert-butylate In 1-methyl-pyrrolidin-2-one at 110℃; for 0.0666667h; Sealed vessel; Microwave irradiation; Inert atmosphere; Stage #2: With hydrogenchloride In water at 0℃; pH=3;	85%
With potassium tert-butylate In 1-methyl-pyrrolidin-2-one at 130℃; for 0.5h;

4-chloronicotinic acid (10177-29-4) + phenylboronic acid (98-80-6) → 4-phenyl-3-pyridinecarboxylic acid (103863-14-5)

Conditions	Yield
With sodium carbonate In ethanol; water at 70℃; for 8h; Catalytic behavior; Suzuki-Miyaura Coupling;	85%
With palladium diacetate; potassium carbonate; triphenylphosphine In 1,4-dioxane; water Reflux; Inert atmosphere;

4-(2-AMINOETHYL)MORPHOLINE (2038-03-1) + 4-chloronicotinic acid (10177-29-4) → 4-chloro-N-(2-morpholinoethyl)nicotinamide (1221489-82-2)

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane Reflux;	84%

4-(3-Aminopropyl)morpholine (123-00-2) + 4-chloronicotinic acid (10177-29-4) → 4-chloro-N-(3-morpholinopropyl)nicotinamide (1202770-39-5)

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane Reflux;	84%

4-chloronicotinic acid (10177-29-4) + methylamine (74-89-5) → 4-(methylamino)nicotinic acid (1075-09-8)

Conditions	Yield
In water at 165℃; for 4h; Microwave irradiation; Biotage Initiator;	83%
In 1,4-dioxane; water at 100℃; for 0.833333h; Microwave irradiation;	74%
In 1,4-dioxane; water at 100℃; for 0.833333h; Microwave irradiation;	74%

4-chloronicotinic acid (10177-29-4) + p-Chlorothiophenol (106-54-7) → 4-(4-chlorophenylthio)nicotinic acid (32896-67-6)

Conditions	Yield
In N,N-dimethyl-formamide at 140 - 145℃; for 4.5h;	81%

4-chloronicotinic acid (10177-29-4) → 4-hydroxynicotinic acid (609-70-1)

Conditions	Yield
With water Heating;	80%
With water	80%

4-chloronicotinic acid (10177-29-4) → 4-hydrazino-nicotinic acid (3323-91-9)

Conditions	Yield
Stage #1: 4-chloronicotinic acid With hydrazine hydrate at 100℃; for 4h; Stage #2: With hydrogenchloride In water pH=5;	78%
With hydrazine hydrate at 100℃; for 4h;

4-chloronicotinic acid (10177-29-4) → 1,4-dihydro-4-oxopyridine-3-carboxylic acid (72676-96-1)

Conditions	Yield
With water for 2h; Reflux;	75%
With water for 2h; Reflux;

4-chloronicotinic acid (10177-29-4) + carbostyril 124 (19840-99-4) → 4-((4-methyl-2-oxo-1,2-dihydroquinolin-7-yl)amino)nicotinic acid

Conditions	Yield
With tin; copper; potassium carbonate Reflux;	73%

morpholine (110-91-8) + 4-chloronicotinic acid (10177-29-4) → potassium 4-morpholinonicotinate

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 120℃; for 12h;	71%
With potassium carbonate In dimethyl sulfoxide at 120℃; for 12h;	71%

2-isopropyliodobenzene (19099-54-8) + 4-chloronicotinic acid (10177-29-4) + diphenyl acetylene (501-65-5) → 7-isopropyl-5,6-diphenylbenzo[f]isoquinoline

Conditions	Yield
With norborn-2-ene; palladium diacetate; potassium carbonate; tris-(o-tolyl)phosphine In N,N-dimethyl-formamide at 130℃; for 20h; Schlenk technique; Inert atmosphere; Sealed tube; regioselective reaction;	69%

Upstream product

• 609-70-1 4-hydroxynicotinic acid 
• 626-61-9 4-Chloropyridine 
• 124-38-9 carbon dioxide 
• 1681-36-3 4-chloro-3-methylpyridine 
• 1074-98-2 3-methyl-4-nitropyridine N-oxide 
• 59-67-6 nicotinic acid 
• 7379-35-3 4-chlorpyridine hydrochloride 
• 114077-82-6 4-chloronicotinaldehyde 
• 1003-73-2 3-picoline-N-oxide 
• 2398-81-4 Nicotinic acid N-oxide 
• 10026-13-8 phosphorus pentachloride 
• 10025-87-3 trichlorophosphate 

Downstream Products

• 80706-26-9 tert-butyl 4-chloronicotinate 
• 119293-22-0 ethyl 3-hydroxyfuro<3,2-c>pyridine-2-carboxylate 
• 67600-18-4 5,10-Dihydro-11H-pyrido<4,3-b>-1,5-benzodiazepin-11-one 
• 63592-85-8 methyl 4-chloronicotinate 
• 10561-89-4 1-methyl-4-oxo-1,4-dihydropyridine-3-carboxylic acid 
• 3268-73-3 1H-Pyrazol<3,4-c>pyridin-3(2H)-on 
• 1581288-72-3 2,3-diamino-4-phenyl-2,7-naphthyridin-1(2H)-one 
• 1581288-74-5 2-(4-hydroxy-3-methoxyphenyl)-10-phenyl-[1,2,4]triazolo[1,5-b][2,7]naphthyridin-5(3H)-one 
• 1581288-75-6 2-(4-methylphenyl)-10-phenyl-[1,2,4]triazolo[1,5-b][2,7]naphthyridin-5(3H)-one 
• 1581288-77-8 2-(3-hydroxy-4-methoxyphenyl)-10-phenyl-[1,2,4]triazolo[1,5-b][2,7]naphthyridin-5(3H)-one 
• 1581288-80-3 2-(4-methoxyphenyl)-10-phenyl-[1,2,4]triazolo[1,5-b][2,7]naphthyridin-5(3H)-one 

Relevant articles and documents

A Parallel Synthesis Approach to the Identification of Novel Diheteroarylamide-Based Compounds Blocking HIV Replication: Potential Inhibitors of HIV-1 Pre-mRNA Alternative Splicing

A 256-compound library was evaluated in an anti-HIV screen to identify structural "mimics"of the fused tetracyclic indole compound 1 (IDC16) that conserve its anti-HIV activity without associated cytotoxicity. Four diheteroarylamide-type compounds, containing a common 5-nitroisobenzothiazole motif, were identified as active. In subsequent screens, the most potent compound 9 (1C8) was active against wild-type HIV-1IIIB (subtype B, X4-tropic) and HIV-1 97USSN54 (subtype A, R5-tropic) with EC50's of 0.6 and 0.9 μM, respectively. Compound 9 also inhibited HIV strains resistant to drugs targeting HIV reverse transcriptase, protease, integrase, and coreceptor CCR5 with EC50's ranging from 0.9 to 1.5 μM. The CC50 value obtained in a cytotoxicity assay for compound 9 was >100 μM, corresponding to a therapeutic index (CC50/EC50) of approximately 100. Further comparison studies revealed that, whereas the anti-HIV activity for compound 9 and the parent molecule 1 are similar, the cytotoxic effect for compound 9 was, as planned, markedly suppressed.

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CHEMICAL MOLECULES THAT INHIBIT THE SLICING MECHANISM FOR TREATING DISEASES RESULTING FROM SPLICING ANOMALIES

The present invention relates to a compound of one of the formulas I to XXI; a pharmaceutical composition comprising at least one such compound; and the use of at least one such compound in preparing a drug to treat, in a subject, a genetic disease resulting from at least one splicing anomaly.

CHEMICAL MOLECULES THAT INHIBIT THE SLICING MECHANISM FOR TREATING DISEASES RESULTING FROM SPLICING ANOMALIES

The present invention relates to a compound of one of the formulas I to XXI; a pharmaceutical composition comprising at least one such compound; and the use of at least one such compound in preparing a drug to treat, in a subject, a genetic disease resulting from at least one splicing anomaly.