benzhydryl (7R)-3-hydroxy-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】22729

【品名】benzhydryl (7R)-3-hydroxy-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

【CA登记号】

【分子式】C₂₈H₂₄N₂O₅S

【分子量】500.57504

【元素组成】C 67.18% H 4.83% N 5.6% O 15.98% S 6.41%

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：(XXVIII)

Synthesis of intermediate (II): 2) The esterification of penicillin G (XXI) with diphenylmetbanol and pyridine gives the corresponding ester (XXII), which is oxidized with H2O2 and formic acid to the sulfoxide (XXIII). The reaction of (XXIII) with trimethyl phosphite in refluxing toluene yields the bicyclic thiazoline (XXIV), which is ozonolyzed with O3 in methanol dichloromethane affording the enol (XXV). The condensation of (XXV) with morpholine by means of p-toluenesulfonyl chloride in THF gives the enamine (XXVI), which by bromination with Br2 in pyridine and hydrolysis with H2SO4 in aqueous methanol is converted to diphenylmethyl 7beta-(phenylacetylamino)-3-hydroxy 3-cephem 4-carboxylate (XXVIII) through the intermediate (XXVII).

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	分子式	供应商	用于合成
(XXI)	22722	(2S)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid	C₁₆H₁₈N₂O₄S	详情	详情
(XXII)	22723	benzhydryl (2S)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate	C₂₉H₂₈N₂O₄S	详情	详情
(XXIII)	22724	benzhydryl (2S)-3,3-dimethyl-4,7-dioxo-6-[(2-phenylacetyl)amino]-4lambda(4)-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate	C₂₉H₂₈N₂O₅S	详情	详情
(XXIV)	22725	benzhydryl 2-(3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3.2.0]hept-2-en-6-yl)-3-methyl-3-butenoate	C₂₉H₂₆N₂O₃S	详情	详情
(XXV)	22726	benzhydryl (E)-2-(3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3.2.0]hept-2-en-6-yl)-3-hydroxy-2-butenoate	C₂₈H₂₄N₂O₄S	详情	详情
(XXVI)	22727	benzhydryl (E)-2-(3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3.2.0]hept-2-en-6-yl)-3-(4-morpholinyl)-2-butenoate	C₃₂H₃₁N₃O₄S	详情	详情
(XXVII)	22728	benzhydryl (E)-4-bromo-3-hydroxy-2-[(3R)-2-oxo-3-[(2-phenylacetyl)amino]-4-sulfanylazetidinyl]-2-butenoate	C₂₈H₂₅BrN₂O₅S	详情	详情
(XXVIII)	22729	benzhydryl (7R)-3-hydroxy-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate	C₂₈H₂₄N₂O₅S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXVIII)

Synthesis of intermediate (II): 2a) The hydrogenation of (XXVIII) with NaBH4 in methanol - dichloromethane yields the cepham derivative (XXIX), which by mesylation with mesyl chloride and hydrolysis with PCl5 and isobutanol is converted to diphenylmethyl 7beta-amino-3-(methanesulfonyloxy)cepham-4-carboxylate (XXX). Finally, this compound is treated with triethylamine or NaHCO3 to obtain the cephem derivative (II). 2b) The elimination of the OH group of (XXVIII) can also be performed by mesylation with mesyl chloride and hydrolysis with PCl5 and isobutanol to give diphenylmethyl 7beta-amino-3-(methanesulfonyloxy)-3-cephem-4-carboxylate (XXXI), which is then treated with Zn in acidic medium to yield cephem derivative (II).

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	分子式	供应商	用于合成
(II)	22690	benzyl (7R)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate	C₁₄H₁₄N₂O₃S	详情	详情
(XXVIII)	22729	benzhydryl (7R)-3-hydroxy-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate	C₂₈H₂₄N₂O₅S	详情	详情
(XXIX)	22730	benzhydryl (7R)-3-hydroxy-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate	C₂₈H₂₄N₂O₅S	详情	详情
(XXX)	22731	benzhydryl (2R,3R,7R)-7-amino-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-8-oxo-5-thia-1-azabicyclo[4.2.0]octane-2-carboxylate	C₂₃H₂₆N₂O₄S₂	详情	详情
(XXXI)	22732	benzhydryl (7R)-7-amino-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate	C₂₃H₂₄N₂O₄S₂	详情	详情

Extended Information