3-(tert-butylsulfanyl)-2-pyridinecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】45486

【品名】3-(tert-butylsulfanyl)-2-pyridinecarboxylic acid

【CA登记号】178811-41-1

【分子式】C₁₀H₁₃NO₂S

【分子量】211.28476

【元素组成】C 56.85% H 6.2% N 6.63% O 15.14% S 15.18%

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：(X)

Borane reduction of 3-tert-butylthiopyridine-2-carboxylic acid (X) provided alcohol (XI), which was chlorinated to (XII) with SOCl2 and subsequently displaced with N-Boc-2-mercaptoethylamine (XIII), yielding thioether (XIV). Acid deprotection of the tert-butyl groups of (XIV), followed by air oxidation in the presence of FeCl3, produced the dimeric disulfide (XV). This was reprotected with Boc2O to afford the biscarbamate (XVI). Disulfide (XVI) was reduced in situ with PPh3 to the corresponding thiol, which was coupled with the cephem mesylate (IX) to produce adduct (XVII). The title compound was finally obtained by cleavage of the protecting groups of (XVII) by means of trifluoroacetic acid.

参考文献中间体

合成目标

【1】 Griffith, D.; Blais, J.; Hevker, S.; Price, M.; Huie, K.; Halas, S.; Cho, A.; Dudley, M.; Lee, V.; Ludwikow, M.; Chen, S.; Chemberland, S.; Glinka, T.; Discovery of novel anti-MRSA cephalosporin RWJ-333441 (MC-04,546). Relationships between structure, antibacterial activity, serum stability, pharmacokinetics and efficacy in a series of (3-heteroarylthio)cephems. 40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000, Toronto) 2000, Abst F-1071.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IX)	45485	benzhydryl (6R,7R)-7-([2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]-2-[(trityloxy)imino]acetyl]amino)-3-[(methylsulfonyl)oxy]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₄₆H₃₈N₆O₁₀S₃	详情	详情
(X)	45486	3-(tert-butylsulfanyl)-2-pyridinecarboxylic acid	178811-41-1	C₁₀H₁₃NO₂S	详情	详情
(XI)	45487	[3-(tert-butylsulfanyl)-2-pyridinyl]methanol		C₁₀H₁₅NOS	详情	详情
(XII)	45488	3-(tert-butylsulfanyl)-2-(chloromethyl)pyridine; tert-butyl 2-(chloromethyl)-3-pyridinyl sulfide		C₁₀H₁₄ClNS	详情	详情
(XIII)	33079	tert-butyl 2-sulfanylethylcarbamate		C₇H₁₅NO₂S	详情	详情
(XIV)	45489	tert-butyl 2-([[3-(tert-butylsulfanyl)-2-pyridinyl]methyl]sulfanyl)ethylcarbamate		C₁₇H₂₈N₂O₂S₂	详情	详情
(XV)	45490	2-[([3-[(2-[[(2-aminoethyl)sulfanyl]methyl]-3-pyridinyl)disulfanyl]-2-pyridinyl]methyl)sulfanyl]ethylamine; 2-[([3-[(2-[[(2-aminoethyl)sulfanyl]methyl]-3-pyridinyl)disulfanyl]-2-pyridinyl]methyl)sulfanyl]-1-ethanamine		C₁₆H₂₂N₄S₄	详情	详情
(XVI)	45491	tert-butyl 2-([[3-([2-[([2-[(tert-butoxycarbonyl)amino]ethyl]sulfanyl)methyl]-3-pyridinyl]disulfanyl)-2-pyridinyl]methyl]sulfanyl)ethylcarbamate		C₂₆H₃₈N₄O₄S₄	详情	详情
(XVII)	45492	benzhydryl (6R,7R)-3-([2-[([2-[(tert-butoxycarbonyl)amino]ethyl]sulfanyl)methyl]-3-pyridinyl]sulfanyl)-7-([2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]-2-[(trityloxy)imino]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₅₈H₅₄N₈O₉S₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

Borane reduction of 3-tert-butylthiopyridine-2-carboxylic acid (X) provided alcohol (XI), which was chlorinated to (XII) with SOCl2 and subsequently displaced with N-Boc-2-mercaptoethylamine (XIII), yielding thioether (XIV). Acid deprotection of the tert-butyl groups of (XIV), followed by air oxidation in the presence of FeCl3, produced the dimeric disulfide (XV). This was acylated with the protected aspartate pentafluorophenyl ester (XVI) to afford the diamide (XVII). Disulfide (XVII) was reduced in situ with PPh3 to the corresponding thiol, which was coupled with the cephem mesylate (IX) to produce adduct (XVIII). The title compound was finally obtained by cleavage of the protecting groups of (XVIII) by means of trifluoroacetic acid.

参考文献中间体

合成目标

【1】 Hecker, S.J.; et al.; Prodrugs of anti-MRSA cephalosporin RWJ-333441 (MC-04,546) with improved aqueous solubility. 40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000, Toronto) 2000, Abst F-1076.
【2】 Griffith, D.; Blais, J.; Hevker, S.; Price, M.; Huie, K.; Halas, S.; Cho, A.; Dudley, M.; Lee, V.; Ludwikow, M.; Chen, S.; Chemberland, S.; Glinka, T.; Discovery of novel anti-MRSA cephalosporin RWJ-333441 (MC-04,546). Relationships between structure, antibacterial activity, serum stability, pharmacokinetics and efficacy in a series of (3-heteroarylthio)cephems. 40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000, Toronto) 2000, Abst F-1071.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IX)	45485	benzhydryl (6R,7R)-7-([2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]-2-[(trityloxy)imino]acetyl]amino)-3-[(methylsulfonyl)oxy]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₄₆H₃₈N₆O₁₀S₃	详情	详情
(X)	45486	3-(tert-butylsulfanyl)-2-pyridinecarboxylic acid	178811-41-1	C₁₀H₁₃NO₂S	详情	详情
(XI)	45487	[3-(tert-butylsulfanyl)-2-pyridinyl]methanol		C₁₀H₁₅NOS	详情	详情
(XII)	45488	3-(tert-butylsulfanyl)-2-(chloromethyl)pyridine; tert-butyl 2-(chloromethyl)-3-pyridinyl sulfide		C₁₀H₁₄ClNS	详情	详情
(XIII)	33079	tert-butyl 2-sulfanylethylcarbamate		C₇H₁₅NO₂S	详情	详情
(XIV)	45489	tert-butyl 2-([[3-(tert-butylsulfanyl)-2-pyridinyl]methyl]sulfanyl)ethylcarbamate		C₁₇H₂₈N₂O₂S₂	详情	详情
(XV)	45490	2-[([3-[(2-[[(2-aminoethyl)sulfanyl]methyl]-3-pyridinyl)disulfanyl]-2-pyridinyl]methyl)sulfanyl]ethylamine; 2-[([3-[(2-[[(2-aminoethyl)sulfanyl]methyl]-3-pyridinyl)disulfanyl]-2-pyridinyl]methyl)sulfanyl]-1-ethanamine		C₁₆H₂₂N₄S₄	详情	详情
(XVI)	45493	4-(tert-butyl) 1-(2,3,4,5,6-pentafluorophenyl) (2S)-2-[(tert-butoxycarbonyl)amino]butanedioate		C₁₉H₂₂F₅NO₆	详情	详情
(XVII)	45494	tert-butyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-([2-[([3-[(2-[(7S)-7-[2-(tert-butoxy)-2-oxoethyl]-11,11-dimethyl-6,9-dioxo-10-oxa-2-thia-5,8-diazadodec-1-yl]-3-pyridinyl)disulfanyl]-2-pyridinyl]methyl)sulfanyl]ethyl]amino)-4-oxobutanoate		C₄₂H₆₄N₆O₁₀S₄	详情	详情
(XVIII)	45495	benzhydryl (6R,7R)-3-[(2-[(7S)-7-[2-(tert-butoxy)-2-oxoethyl]-11,11-dimethyl-6,9-dioxo-10-oxa-2-thia-5,8-diazadodec-1-yl]-3-pyridinyl)sulfanyl]-7-([2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]-2-[(trityloxy)imino]acetyl]amino)-8-oxo-5-thia-1		C₆₆H₆₇N₉O₁₂S₄	详情	详情

Extended Information