bromo(chloro)methane -Drug Synthesis Database

【结构式】

【分子编号】19740

【品名】bromo(chloro)methane

【CA登记号】74-97-5

【分子式】CH₂BrCl

【分子量】129.38358

【元素组成】C 9.28% H 1.56% Br 61.76% Cl 27.4%

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：

2) The condensation of 1,2,3-triazol-4-thiol (X) with bromochloromethane by means of NaH gives 4-(chloromethylsulfanyl)-1,2,3-triazole (XI) with is treated with NaI in hot acetone to afford 4-(iodomethylsulfanyl)-1,2,3-triazole (XII). The reaction of (XII) with the silver mercaptide of the 7beta-[2-[2-(tert-butoxycarbonylamino)thiazol-4-yl]-2(Z)-(triphenylmethoxyimino)acetamido]-3-sulfanyl-3-cephem-4-carboxylic acid diphenylmethyl ester 1beta-oxide (XIII) in HMPT yields the condensation product (XV), which is then treated with PCl3 in DMF to eliminate the 1beta-oxide oxygen, affording the protected compound (XVI), which is deprotected with AlCl3 in anisole, as before.

参考文献中间体

合成目标

【1】 Mealy, N.; Castaner, J.; S-1090. Drugs Fut 1996, 21, 3, 254.
【2】 Kubota, T.; Kume, M. (Shionogi & Co. Ltd.); Thioalkylthio cephalosporin derivs. EP 0467647; JP 1992234346; JP 1993059066; US 5214037 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	19740	bromo(chloro)methane	74-97-5	CH₂BrCl	详情	详情
(X)	15898	1H-1,2,3-triazole-4-thiol; 1H-1,2,3-triazol-4-ylhydrosulfide		C₂H₃N₃S	详情	详情
(XI)	15899	4-[(chloromethyl)sulfanyl]-1H-1,2,3-triazole; chloromethyl 1H-1,2,3-triazol-4-yl sulfide		C₃H₄ClN₃S	详情	详情
(XII)	15900	iodomethyl 1H-1,2,3-triazol-4-yl sulfide; 4-[(iodomethyl)sulfanyl]-1H-1,2,3-triazole		C₃H₄IN₃S	详情	详情
(XIII)	15901	7beta-[2-[2-(tert-butoxycarbonylamino)thiazol-4-yl]-2(Z) -(triphenylmethoxyimino)acetamido]-3-sulfanyl-3-cephem-4-carboxylic acid dibenzyl ester 1beta-oxide; (6R,7R)-7-[2-[2-(Tert-butoxycarbonylamino)thiazol-4-yl]-2-(triphenylmethoxyimino)acetamido]-3-sulfanyl-3-cephem-4-carboxylic acid dibenzyl ester 1-oxide silver salt		C₄₉H₄₂AgN₅O₈S₃	详情	详情
(XIV)	15902	benzhydryl (6R,7R)-7-([2-[2-[(tert-butoxycarbonyl)amino]-1,3-thiazol-4-yl]-2-[(trityloxy)imino]acetyl]amino)-5,8-dioxo-3-sulfanyl-5lambda(4)-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₄₉H₄₃N₅O₈S₃	详情	详情
(XV)	15903	benzhydryl (6R,7R)-7-([2-[2-[(tert-butoxycarbonyl)amino]-1,3-thiazol-4-yl]-2-[(trityloxy)imino]acetyl]amino)-5,8-dioxo-3-[[(1H-1,2,3-triazol-4-ylsulfanyl)methyl]sulfanyl]-5lambda(4)-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₅₂H₄₆N₈O₈S₄	详情	详情
(XVI)	15904	benzhydryl (6R,7R)-7-([2-[2-[(tert-butoxycarbonyl)amino]-1,3-thiazol-4-yl]-2-[(trityloxy)imino]acetyl]amino)-8-oxo-3-[[(1H-1,2,3-triazol-4-ylsulfanyl)methyl]sulfanyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₅₂H₄₆N₈O₇S₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XV)

Palinavir can also be obtained as follows: The controlled oxidation of 2(S)-(dibenzylamino)-3-phenyl-1-propanol (XIII) with pyridine-SO3 complex in DMSO gives the corresponding aldehyde (XIV), which is condensed with bromochloromethane (XV) by means of Li in THF followed by hydrolysis with HCl yielding regioselectively the 1-chloro-2-butanol (XVI). The debenzylation of (XVI) by hydrogenation over Pd/C affords the free amine (XVII), which is treated with tert-butoxycarbonyl anhydride/triethylamine and dehydrochlorinated with KOH in methanol to give the desired chiral epoxide (V).

参考文献中间体

合成目标

【1】 Beaulieu, P.L.; et al.; Practical, stereoselective synthesis of palinavir, a potent HIV protease inhibitor. J Org Chem 1997, 62, 11, 3440.
【2】 Gillard, J.; et al.; Preparation of (2S,4R)-4-hydroxypipecolic acid and derivatives. J Org Chem 1996, 61, 6, 2226.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	19730	tert-butyl (1S)-1-[(2S)oxiranyl]-2-phenylethylcarbamate	98737-29-2	C₁₅H₂₁NO₃	详情	详情
(XIII)	19738	(2S)-2-[bis(4-methylphenyl)amino]-3-phenyl-1-propanol		C₂₃H₂₅NO	详情	详情
(XIV)	19739	(2S)-2-[bis(4-methylphenyl)amino]-3-phenylpropanal		C₂₃H₂₃NO	详情	详情
(XV)	19740	bromo(chloro)methane	74-97-5	CH₂BrCl	详情	详情
(XVI)	19741	(2S,3S)-3-[bis(4-methylphenyl)amino]-1-chloro-4-phenyl-2-butanol		C₂₄H₂₆ClNO	详情	详情
(XVII)	19742	(2S,3S)-3-amino-1-chloro-4-phenyl-2-butanol		C₁₀H₁₄ClNO	详情	详情

Extended Information