1-benzhydryl 5-benzyl (Z)-2-(2-[[(benzyloxy)carbonyl]amino]-1,3-thiazol-4-yl)-2-pentenedioate -Drug Synthesis Database

【结构式】

【分子编号】22721

【品名】1-benzhydryl 5-benzyl (Z)-2-(2-[[(benzyloxy)carbonyl]amino]-1,3-thiazol-4-yl)-2-pentenedioate

【CA登记号】

【分子式】C₃₆H₃₀N₂O₆S

【分子量】618.71008

【元素组成】C 69.89% H 4.89% N 4.53% O 15.52% S 5.18%

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：(XX)

Synthesis of intermediate (I): 1c) The bromination of diketene (XIII) followed by reaction with diphenylmethanol gives diphenylmethyl 4-bromoacetoacetate (XIV), which by cyclization with thiourea by means of K2CO3 yields diphenylmethyl 2-(2-aminothiazol-4-yl)acetate (XV). The reaction of (XV) with benzyloxycarbonyl chloride and pyridine affords the protected compound (XVI), which is formylated with diphenyl methyl formiate (XVII) and NaH to afford diphenyl methyl 2-(2-benzyloxycarbonylamino)thiazol-4-yl-3-hydroxyacrylate (XVIII) The Wittig condensation of (XVIII) with benzyl triphenylphosphoranylidene acetate (XIX) gives diphenylmethyl 2-[2-(benzyloxycarbonylamino)thiazol-4-yl]-4-(benzyloxycarbonyl)-2-butenoate (XX), which is selectively hydrolyzed with trifluoroacetic acid and anisole lo acid.

参考文献中间体

合成目标

【1】 Yoshioka, M.; Synthetic studies related to oral beta-lactam antibiotics. Pure Appl Chem 1987, 59, 8, 1041.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10180	Thiourea	62-56-6	CH₄N₂S	详情	详情
(I)	22689	(Z)-5-(benzyloxy)-2-(2-[[(benzyloxy)carbonyl]amino]-1,3-thiazol-4-yl)-5-oxo-2-pentenoic acid		C₂₃H₂₀N₂O₆S	详情	详情
(XIII)	11367	4-Methylene-2-oxetanone; Acetyl ketene	674-82-8	C₄H₄O₂	详情	详情
(XIV)	22715	benzhydryl 4-bromo-3-oxobutanoate		C₁₇H₁₅BrO₃	详情	详情
(XV)	22716	benzhydryl 2-amino-1,3-thiazole-4-carboxylate		C₁₇H₁₄N₂O₂S	详情	详情
(XVI)	22717	benzhydryl 2-[[(benzyloxy)carbonyl]amino]-1,3-thiazole-4-carboxylate		C₂₅H₂₀N₂O₄S	详情	详情
(XVII)	22718	benzhydryl formate		C₁₄H₁₂O₂	详情	详情
(XVIII)	22719	benzhydryl (Z)-2-(2-[[(benzyloxy)carbonyl]amino]-1,3-thiazol-4-yl)-3-hydroxy-2-propenoate		C₂₇H₂₂N₂O₅S	详情	详情
(XIX)	22668	benzyl 2-(triphenylphosphoranylidene)acetate		C₂₇H₂₃O₂P	详情	详情
(XX)	22721	1-benzhydryl 5-benzyl (Z)-2-(2-[[(benzyloxy)carbonyl]amino]-1,3-thiazol-4-yl)-2-pentenedioate		C₃₆H₃₀N₂O₆S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The Wittig condensation of diphenylmethyl 2-[2-(benzyloxycarbonylamino)thiazol-4 yl-2-formyl acetate with benzyloxycarbonylmethylene triphenylphosphorane (II) in toluene or dioxane gives 2-[2-(benzyloxycarbonylamino)thiazol-4-yl]-4 (benzyloxycarbonyl)-2-butenoic acid diphenylmethyl ester (III), which is hydrolyzed partiaily wth trifluoroacetic acid and anisole to the 2-butenoic acid (IV). The condensation of (IV) with 7-beta-amino-3-cephem-4-carboxylic acid benzyl ester (V) by means of dicyclohexylcarbodiimide (DCC) in dichloromethane affords the protected final product (VI), which is finally debenzylated by means of AlCl3 and anisole in methylene chloride.

参考文献中间体

合成目标

【1】 Yoshida, T.; Synthesis and biological properties of 7Beta-[(Z)-2-(2-amino-4-thiazoyl)-4-carboxy-2-butenoylamino]-3-cephem-4-carboxilic acid (7432-S), a new oral cephem antibiotic. J Antibiot 1987, 40, 10, 1468.
【2】 Hamashima, Y. (Shionogi & Co. Ltd.); 7-Carboxyalkenoylamido-3-cephem-4-carboxylic acid derivs.. EP 0136721; ES 8604602; ES 8605278; ES 8700222; GB 2154580; GB 2198727; JP 1985078987; JP 1985163884; JP 1985246388; US 4634697; US 4748170 .
【3】 Castaner, J.; Prous, J.; 7432-S. Drugs Fut 1987, 12, 12, 1117.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	24153	benzhydryl 2-(2-[[(benzyloxy)carbonyl]amino]-1,3-thiazol-4-yl)-3-oxopropanoate	C₂₇H₂₂N₂O₅S	详情	详情
(II)	22668	benzyl 2-(triphenylphosphoranylidene)acetate	C₂₇H₂₃O₂P	详情	详情
(III)	22721	1-benzhydryl 5-benzyl (Z)-2-(2-[[(benzyloxy)carbonyl]amino]-1,3-thiazol-4-yl)-2-pentenedioate	C₃₆H₃₀N₂O₆S	详情	详情
(IV)	22689	(Z)-5-(benzyloxy)-2-(2-[[(benzyloxy)carbonyl]amino]-1,3-thiazol-4-yl)-5-oxo-2-pentenoic acid	C₂₃H₂₀N₂O₆S	详情	详情
(V)	24157	benzyl (6R,7R)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate	C₁₄H₁₄N₂O₃S	详情	详情
(VI)	24158	benzyl (6R,7R)-7-[[(Z)-5-(benzyloxy)-2-(2-[[(benzyloxy)carbonyl]amino]-1,3-thiazol-4-yl)-5-oxo-2-pentenoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate	C₃₇H₃₂N₄O₈S₂	详情	详情

Extended Information