2-chloro-3-pyridinesulfonyl chloride -Drug Synthesis Database

【结构式】

【分子编号】64113

【品名】2-chloro-3-pyridinesulfonyl chloride

【CA登记号】

【分子式】C₅H₃Cl₂NO₂S

【分子量】212.05576

【元素组成】C 28.32% H 1.43% Cl 33.44% N 6.61% O 15.09% S 15.12%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VI)

Bromination of 2-amino-5-methylpyrazine (I) with Br2 in CHCl3 affords the bromopyrazine (II). Subsequent bromide displacement in (II) by means of sodium methoxide gives rise to the methoxypyrazine (III). The amino group of (III) is then protected by acylation with isobutyl chloroformate, to produce carbamate (IV). Diazotization of 3-amino-2-chloropyridine (V), followed by treatment with sulfur dioxide in the presence of CuCl furnishes sulfonyl chloride (VI). Carbamate (IV) is then acylated by means of NaH and sulfonyl chloride (VI) in DMF to furnish the N-sulfonyl carbamate (VII). Esterification of 4-carboxyphenylboronic acid (VIII) with H2SO4 in MeOH gives 4-(methoxycarbonyl)phenylboronic acid (IX). Mitsunobu coupling between boronic acid (IX) and chloropyridine (VII) furnishes adduct (X). Methyl ester (X) is converted into hydrazide (XI) by treatment with hydrazine hydrate in refluxing methanol. Then, cyclization of the acyl hydrazide (XI) with boiling triethyl orthoformate gives rise to the target oxadiazole derivative.

参考文献中间体

合成目标

【1】 Bradbury, R.H.; Butlin, R.J.; James, R. (AstraZeneca plc); N-Heteroaryl-pyridinesulfonamide derivs. and their use as endothelin antagonists. EP 0832082; JP 1999509175; US 6060475; US 6258817; WO 9640681 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	64109	5-methyl-2-pyrazinamine; 5-methyl-2-pyrazinylamine		C₅H₇N₃	详情	详情
(II)	64110	3-bromo-5-methyl-2-pyrazinamine; 3-bromo-5-methyl-2-pyrazinylamine		C₅H₆BrN₃	详情	详情
(III)	64111	5-methyl-3-(methyloxy)-2-pyrazinamine; 5-methyl-3-(methyloxy)-2-pyrazinylamine		C₆H₉N₃O	详情	详情
(IV)	64112	2-methylpropyl 5-methyl-3-(methyloxy)-2-pyrazinylcarbamate		C₁₁H₁₇N₃O₃	详情	详情
(V)	11160	2-Chloro-3-pyridinamine; 2-Chloro-3-pyridinylamine; 3-Amino-2-chloropyridine; 2-Chloro-3-aminopyridine	6298-19-7	C₅H₅ClN₂	详情	详情
(VI)	64113	2-chloro-3-pyridinesulfonyl chloride		C₅H₃Cl₂NO₂S	详情	详情
(VII)	64115	2-methylpropyl (2-chloro-3-pyridinyl)sulfonyl[5-methyl-3-(methyloxy)-2-pyrazinyl]carbamate		C₁₆H₁₉ClN₄O₅S	详情	详情
(VIII)	32841	4-(dihydroxyboryl)benzoic acid；4-Boronobenzoic acid；4-carboxyphenylboronic acid;4-(Dihydroxyboryl)benzoic acid	14047-29-1	C₇H₇BO₄	详情	详情
(IX)	64114	4-[(methyloxy)carbonyl]phenylboronic acid		C₈H₉BO₄	详情	详情
(X)	64116	methyl 4-{3-[([5-methyl-3-(methyloxy)-2-pyrazinyl]{[(2-methylpropyl)oxy]carbonyl}amino)sulfonyl]-2-pyridinyl}benzoate		C₂₄H₂₆N₄O₇S	详情	详情
(XI)	64117	2-[4-(hydrazinocarbonyl)phenyl]-N-[5-methyl-3-(methyloxy)-2-pyrazinyl]-3-pyridinesulfonamide		C₁₈H₁₈N₆O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XV)

Bromination of 2-amino-5-methylpyrazine (X) with Br2 in CHCl3 affords the bromopyrazine (XI), which by subsequent bromide displacement by means of sodium methoxide in refluxing methanol gives the methoxypyrazine (XII). Then, the amino group of (XII) is protected by acylation with isobutyl chloroformate (XIII) in the presence of pyridine in CH2Cl2 to provide carbamate (XIV), which finally, after being pretreated with NaH, is sulfonylated with 2-chloropyridine-3-sulfonyl chloride (XV) in DMF. Compound (XV) is prepared from 3-amino-2-chloropyridine (XVI) by diazotization and subsequent treatment with sulfur dioxide in the presence of CuCl in AcOH .

参考文献中间体

合成目标

【1】 Bradbury, R.H., Butlin, R.J., James, R. (AstraZeneca plc). N-Heteroarylpyridinesulfonamide derivatives and their use as endothelin antagonists. EP 0832082, JP 1999509175, US 6060475, US 6258817, WO 1996040681.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	69329	isobutyl (2-chloropyridin-3-yl)sulfonyl(3-methoxy-5-methyl-4,5-dihydropyrazin-2-yl)carbamate		C₁₆H₂₁ClN₄O₅S	详情	详情
(X)	64109	5-methyl-2-pyrazinamine; 5-methyl-2-pyrazinylamine		C₅H₇N₃	详情	详情
(XI)	64110	3-bromo-5-methyl-2-pyrazinamine; 3-bromo-5-methyl-2-pyrazinylamine		C₅H₆BrN₃	详情	详情
(XII)	64111	5-methyl-3-(methyloxy)-2-pyrazinamine; 5-methyl-3-(methyloxy)-2-pyrazinylamine		C₆H₉N₃O	详情	详情
(XIII)	13423	1-[(Chlorocarbonyl)oxy]-2-methylpropane; Isobutyl chloroformate;isobutyl carbonochloridate	543-27-1	C₅H₉ClO₂	详情	详情
(XIV)	64112	2-methylpropyl 5-methyl-3-(methyloxy)-2-pyrazinylcarbamate		C₁₁H₁₇N₃O₃	详情	详情
(XV)	64113	2-chloro-3-pyridinesulfonyl chloride		C₅H₃Cl₂NO₂S	详情	详情
(XVI)	11160	2-Chloro-3-pyridinamine; 2-Chloro-3-pyridinylamine; 3-Amino-2-chloropyridine; 2-Chloro-3-aminopyridine	6298-19-7	C₅H₅ClN₂	详情	详情

Extended Information