6636-55-1

Basic information

• Product Name: 6-CHLORO-2-PICOLINIC ACID METHYL ESTER
• Synonyms: Methyl 6-Chloropyridine-2-carboxylate, 97+%;METHYL 6-CHLOROPYRIDINE-2-CARBOXYLATE;AKOS BBS-00004651;6-CHLOROPYRIDINE-2-CARBOXYLIC ACID METHYL ESTER;6-CHLORO-2-PICOLINIC ACID METHYL ESTER;methyl 6-chloro-2-pyridinecarboxylate;6-Chloro-2-pyridinecarboxylic acid methyl ester;6-Chloropicolinic acid methyl ester
• CAS NO: 6636-55-1
• Molecular Formula: C₇H₆ClNO₂
• Molecular Weight: 171.58
• EINECS: -0
• Product Categories: Picolinic acid series
• Mol File: 6636-55-1.mol
• Article Data: 15

Chemical Properties

• Melting Point: 93-94°
• Boiling Point: 275.832oC at 760 mmHg
• Flash Point: 120.619oC
• Appearance: Pale yellow/Solid
• Density: 1.295g/cm3
• Vapor Pressure: 0.005mmHg at 25°C
• Refractive Index: 1.531
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• PKA: -1.03±0.10(Predicted)
• Water Solubility: Slightly soluble in water.
• CAS DataBase Reference: 6-CHLORO-2-PICOLINIC ACID METHYL ESTER(CAS DataBase Reference)
• NIST Chemistry Reference: 6-CHLORO-2-PICOLINIC ACID METHYL ESTER(6636-55-1)
• EPA Substance Registry System: 6-CHLORO-2-PICOLINIC ACID METHYL ESTER(6636-55-1)

Safety Data

• HazardClass: IRRITANT
• Hazardous Substances Data: 6636-55-1(Hazardous Substances Data)

Usage

Uses

Methyl 6-chloropyridine-2-carboxylate was coupled with 2-(trimethylstannyl)pyridine to afford methyl 2,2?-bipyridine-6-carboxylate.

Synthesis Reference(s)

Synthetic Communications, 14, p. 77, 1984 DOI: 10.1080/00397918408060867

InChI:InChI=1/C7H6ClNO2/c1-11-7(10)5-3-2-4-6(8)9-5/h2-4H,1H3

Synthetic route

methanol (67-56-1) + 6-chloropicolinic acid (4684-94-0) → methyl 6-chloropicolinate (6636-55-1)

Conditions	Yield
With thionyl chloride at 0 - 50℃; for 6.75h;	100%
Stage #1: methanol; 6-chloropicolinic acid With hydrogenchloride for 15h; Heating / reflux; Stage #2: With sodium hydroxide In water	95%
With hydrogenchloride In water at 80℃; for 48h;
With hydrogenchloride In water at 80℃; for 48h;

6-chloropicolinic acid (4684-94-0) + Methyl trichloroacetate (598-99-2) → methyl 6-chloropicolinate (6636-55-1)

Conditions	Yield
With 18-crown-6 ether; potassium carbonate at 90 - 150℃; for 2h;	83%

2,6-dichloropyridine (2402-78-0) + methanol (67-56-1) + carbon monoxide (201230-82-2) → 2,6-bis(methoxycarbonyl)pyridine (5453-67-8) + methyl 6-chloropicolinate (6636-55-1)

Conditions	Yield
With triethylamine; triphenylphosphine; bis-triphenylphosphine-palladium(II) chloride at 140℃; under 37503 Torr; for 6h; methoxycarbonylation;	A 81% B n/a

methyl 2-hydroxy-6-pyridinecarboxylate (30062-34-1) → methyl 6-chloropicolinate (6636-55-1)

Conditions	Yield
With trichlorophosphate at 110℃; for 14h;	61%

methyl pyridine-2-carboxylate (2459-07-6) + p-nitrophenyl isocyanide (1984-23-2) → methyl 6-chloropicolinate (6636-55-1) + methyl 6-((4-nitrophenyl)carbamoyl)picolinate + 6-(4-nitro-phenylaminooxalyl)-pyridine-2-carboxylic acid methyl ester

Conditions	Yield
Stage #1: methyl pyridine-2-carboxylate With fluorine In dichloromethane at -78 - -50℃; Stage #2: p-nitrophenyl isocyanide In dichloromethane at -50 - 0℃; for 4h;	A 40% B 31% C n/a

6-chloropicolinic acid (4684-94-0) → methyl 6-chloropicolinate (6636-55-1)

Conditions	Yield
With hydrogenchloride
Multi-step reaction with 2 steps 1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 3 h / 20 °C 2: dichloromethane / 1.58 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 3 h / 20 °C 2: 1.5 h / 20 °C View Scheme

2,6-Dibromopyridine (626-05-1) + methanol (67-56-1) + carbon dioxide (124-38-9) → 2,6-bis(methoxycarbonyl)pyridine (5453-67-8) + methyl 6-chloropicolinate (6636-55-1)

Conditions	Yield
With hydrogenchloride; n-butyllithium Yield given. Multistep reaction. Yields of byproduct given;

6-chloropicolinic acid (4684-94-0) + boron trifluoride methanol complex (16045-88-8, 373-57-9) → methyl 6-chloropicolinate (6636-55-1)

Conditions	Yield
at 110℃; for 0.25h;

1-oxy-pyridine-2-carboxylic acid methyl ester (38195-81-2) → methyl 6-chloropicolinate (6636-55-1) + 4-Chloro-pyridine-2-carboxylic acid methyl ester (24484-93-3)

Conditions	Yield
With trichlorophosphate at 80℃; for 17h; Yield given. Yields of byproduct given;

methyl pyridine-2-carboxylate (2459-07-6) → methyl 6-chloropicolinate (6636-55-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: mCPBA / CH2Cl2 / 48 h / Ambient temperature 2: POCl3 / 17 h / 80 °C View Scheme

methanol (67-56-1) + 6-chloropicolinoyl chloride (80099-98-5) → methyl 6-chloropicolinate (6636-55-1)

Conditions	Yield
In dichloromethane at 20℃; for 1.58333h;
at 20℃; for 1.5h;

methyl 6-chloropicolinate (6636-55-1) + 2-(1-(tert-butyldimethylsilyloxy)-3-(4-(phenoxymethyl)phenyl)propyl)-5-(tributylstannyl)oxazole (1012330-50-5) → methyl 6-(2-(1-(tert-butyldimethylsilyloxy)-3-(4-(phenoxymethyl)phenyl)propyl)oxazol-5-yl)pyridine-2-carboxylate (1012330-64-1)

Conditions	Yield
tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane for 3h; Stille coupling; Heating;	95%

methyl 6-chloropicolinate (6636-55-1) + Diphenylphosphine oxide (4559-70-0) → methyl 6-(diphenylphosphoryl)picolinate

Conditions	Yield
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; potassium carbonate In N,N-dimethyl-formamide at 120℃; for 7h; Schlenk technique; Inert atmosphere;	92%

methyl 6-chloropicolinate (6636-55-1) → 6-chloro-2-pyridinemethanol (33674-97-4)

Conditions	Yield
Stage #1: methyl 6-chloropicolinate With lithium aluminium tetrahydride In tetrahydrofuran at -45 - 0℃; for 1.5h; Stage #2: With sodium hydroxide; water In tetrahydrofuran	91%
With sodium tetrahydroborate In ethanol at 15 - 30℃; for 6h; Inert atmosphere;

oxisoindole (480-91-1) + methyl 6-chloropicolinate (6636-55-1) → methyl 6-(1-oxoisoindolin-2-yl)picolinate

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In 1,4-dioxane at 80℃; Inert atmosphere; Sealed tube;	83%

methyl 6-chloropicolinate (6636-55-1) + 2-(3-(biphenyl-4-yl)-1-(tert-butyldimethylsilyloxy)propyl)-5-(tributylstannyl)oxazole (1012330-00-5) → methyl 6-(2-(3-(biphenyl-4-yl)-1-(tert-butyldimethylsilyloxy)propyl)oxazol-5-yl)picolinate (1012330-16-3)

Conditions	Yield
tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane for 24h; Stille coupling; Heating;	81%

4-ethylpiperazine (5308-25-8) + methyl 6-chloropicolinate (6636-55-1) → methyl 6-[4-(2-{[6-(methoxycarbonyl)pyridin-2-yl]sulfanyl}ethyl)piperazin-1-yl]pyridine-2-carboxylate

Conditions	Yield
With sodiumsulfide nonahydrate; sodium acetate In N,N-dimethyl-formamide at 70℃; for 12h;	78%

methyl 6-chloropicolinate (6636-55-1) + 2-(1-(tert-butyldimethylsilyloxy)-3-(4-phenoxyphenyl)propyl)-5-(tributylstannyl)oxazole (1012330-30-1) → methyl 6-(2-(1-(tert-butyldimethylsilyloxy)-3-(4-phenoxyphenyl)propyl)oxazol-5-yl)pyridine-2-carboxylate (1012330-44-7)

Conditions	Yield
tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane for 18h; Stille coupling; Heating;	77%

methyl 6-chloropicolinate (6636-55-1) + sodium thiomethoxide (5188-07-8) → methyl 6-(methylthio)picolinate (74470-41-0)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 0.5h;	72%

methyl 6-chloropicolinate (6636-55-1) + 2-(3-(biphenyl-4-yl)propyl)-5-(tributylstannyl)oxazole (1012331-08-6) → C25H22N2O3 (1012329-80-4)

Conditions	Yield
tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane for 24h; Stille coupling; Heating;	66%

methyl 6-chloropicolinate (6636-55-1) → 6-chloro-pyridine-2-carboxylic acid hydrazide (98142-19-9)

Conditions	Yield
With hydrazine hydrate In methanol at 20℃; for 0.333333h;	65%
With ethanol; hydrazine

methyl 6-chloropicolinate (6636-55-1) + 2-trimethylstannylpyridine (13737-05-8) → 2,2'-dipyridyl-6-carboximidic acid methyl ester (203573-76-6)

Conditions	Yield
bis-triphenylphosphine-palladium(II) chloride In N,N-dimethyl-formamide at 130℃; for 12h; Condensation;	61%

methyl 6-chloropicolinate (6636-55-1) + t-butoxycarbonylhydrazine (870-46-2) → methyl 6-[1-(tert-butoxycarbonyl)hydrazino]pyridine-2-carboxylate

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In toluene at 100℃; Inert atmosphere;	57%

2-(tert-butoxycarbonylamino)-3-phenylpropionic acid (4530-18-1) + methyl 6-chloropicolinate (6636-55-1) → methyl 6-[1-(tert-butoxycarbonylamino)-2-phenyl-ethyl]pyridine-2-carboxylate

Conditions	Yield
With (1,2-dimethoxyethane)dichloronickel(II); [4,4’-bis(1,1-dimethylethyl)-2,2’-bipyridine-N1,N1‘]bis [3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate; caesium carbonate; 4,4'-di-tert-butyl-2,2'-bipyridine In N,N-dimethyl-formamide at 25 - 27℃; for 21h; Reagent/catalyst; Inert atmosphere; Irradiation;	57%

methyl 6-chloropicolinate (6636-55-1) → methyl 6-(5-methyl-2-phenyl-4-oxazolyl)methoxy-2-pyridinecarboxylate

Conditions	Yield
Stage #1: [5-methyl-2-phenyl-1,3-oxazol-4-yl]methanol With sodium hydride In tetrahydrofuran at 1 - 30℃; Stage #2: methyl 6-chloropicolinate In tetrahydrofuran at 1 - 40℃; for 5h;	51%

[5-methyl-2-phenyl-1,3-oxazol-4-yl]methanol (70502-03-3) + methyl 6-chloropicolinate (6636-55-1) → methyl 6-(5-methyl-2-phenyl-4-oxazolyl)methoxy-2-pyridinecarboxylate

Conditions	Yield
Stage #1: [5-methyl-2-phenyl-1,3-oxazol-4-yl]methanol With sodium hydride In tetrahydrofuran at 0 - 20℃; for 0.25h; Stage #2: methyl 6-chloropicolinate In tetrahydrofuran at 40℃; for 5h;	51%

methyl 6-chloropicolinate (6636-55-1) + 2-fluoropyrazine (4949-13-7) → (6-chloropyridin-2-yl)(3-fluoropyrazin-2-yl)methanone (1321427-42-2)

Conditions	Yield
Stage #1: 2-fluoropyrazine With 2,2,6,6-tetramethyl-piperidine; n-butyllithium In tetrahydrofuran at -78 - 0℃; Inert atmosphere; Stage #2: methyl 6-chloropicolinate In tetrahydrofuran at -78 - -70℃;	46%

methyl 6-chloropicolinate (6636-55-1) + d(4)-methanol (811-98-3) → ([2H3]methyl)-6-([2H3]methoxy)picolinate

Conditions	Yield
With potassium tert-butylate at 20 - 50℃; for 43h;	41.6%

methyl 6-chloropicolinate (6636-55-1) + acetonitrile (75-05-8) → 3-(6-chloro-pyridin-2-yl)-3-oxo-propionitrile (1316122-47-0)

Conditions	Yield
With sodium hydride In toluene; mineral oil at 65℃; for 24h; Inert atmosphere;	40%
With sodium hydride In toluene; mineral oil at 65℃; for 24h; Inert atmosphere;	40%

methyl 6-chloropicolinate (6636-55-1) + butan-1-ol (71-36-3) → 6-n-butoxy-2-pyridinecarboxylic acid (83282-26-2)

Conditions	Yield
Stage #1: methyl 6-chloropicolinate; butan-1-ol With sodium hexamethyldisilazane at 130℃; for 48h; Heating / reflux; Stage #2: With hydrogenchloride; water at 0℃;

1-[(tert-butyldimethylsilyl)oxy]-1-(oxazol-2-yl)-7-phenylheptane (808134-96-5) + methyl 6-chloropicolinate (6636-55-1) → methyl 6-(2-(1-(tert-butyldimethylsilyloxy)-7-phenylheptyl)oxazol-5-yl)picolinate (935265-52-4)

Conditions	Yield
Stage #1: 1-[(tert-butyldimethylsilyl)oxy]-1-(oxazol-2-yl)-7-phenylheptane With tert.-butyl lithium Stage #2: With tributyltin chloride Stage #3: methyl 6-chloropicolinate; tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane for 24h; Stille coupling; Heating; Further stages.;	975 mg

Upstream product

• 4684-94-0 6-chloropicolinic acid 
• 626-05-1 2,6-Dibromopyridine 
• 67-56-1 methanol 
• 124-38-9 carbon dioxide 
• 38195-81-2 1-oxy-pyridine-2-carboxylic acid methyl ester 
• 2402-78-0 2,6-dichloropyridine 
• 201230-82-2 carbon monoxide 
• 2459-07-6 methyl pyridine-2-carboxylate 
• 1984-23-2 p-nitrophenyl isocyanide 
• 80099-98-5 6-chloropicolinoyl chloride 
• 30062-34-1 methyl 6-hydroxypyridine-2-carboxylate 
• 16045-88-8 boron trifluoride methanol complex 
• 598-99-2 Methyl trichloroacetate 

Downstream Products

• 98142-19-9 6-chloropyridine-2-carbohydrazide 
• 203573-76-6 2,2'-dipyridyl-6-carboximidic acid methyl ester 
• 602280-11-5 methyl 6-[(1-benzyl-1H-indazol-3-yl)oxy]-2-pyridinecarboxylate 
• 1012330-64-1 methyl 6-(2-(1-(tert-butyldimethylsilyloxy)-3-(4-(phenoxymethyl)phenyl)propyl)oxazol-5-yl)pyridine-2-carboxylate 
• 1012329-80-4 C₂₅H₂₂N₂O₃ 
• 136227-55-9 methyl-6-(3-α,α,α-trifluoromethylphenoxy)-picolinate 
• 63763-79-1 2-chloro-6-(bromomethyl)pyridine 
• 105243-77-4 (6-(methylamino)pyrid-2-yl)methanol 
• 40472-97-7 2-(6-chloro-pyridin-2-yl)-propan-2-ol 

Relevant articles and documents

Gas chromatographic assay and disposition of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, in healthy volunteers

Quantitative determinations of plasma concentrations of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, and its urinary metabolite, 6-chloro-2-pyridinecarboxylic acid (metabolite 1), were obtained using GC with a 63Ni electron-capture detector. 6-Chloro-2-pyridylmethyl nitrate was extracted from plasma with n-pentane. Metabolite 1 was extracted from acidic urine with ethylacetate, back extracted with 0.1 M NaHCO3, and methylated with boron trifluoride methanol reagent. The internal standard for metabolite 1 determination was prepared by propylation of metabolite 1 with boron trifluoride n-propanol reagent. The formation of the esters was confirmed by the GC-MS results. These methods proved to be sensitive and reproducible. A single dose of 6-chloro-2-pyridylmethyl nitrate (5, 10, 20, 40, or 60 mg) was given perorally to healthy volunteers. From the data, a large interindividual variability in the apparent plasma clearance was apparent (85.5 ± 123 L/min; CV 144%). However, metabolite 1 was the main metabolite in human urine, and the interindividual variation was slight (CV 13%).

CXCR4 Receptor Antagonists

Disclosed are compounds that are antagonists of the CXCR4 receptor.

CXCR4 RECEPTOR ANTAGONISTS

The compounds of formula (I) are antagonists of the CXCR4 receptor Wherein R1, X, Y and R2 are as defined in the claims.