• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】53347

【品名】tert-butyl (4S)-4-({7-[2-(benzyloxy)-5-((2S)-2-{[(benzyloxy)carbonyl]amino}-3-methoxy-3-oxopropyl)phenyl]-2-oxo-1,2-dihydro-3H-indol-3-ylidene}methyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate

【CA登记号】n/a

【 分 子 式 】C44H47N3O9

【 分 子 量 】761.872

【元素组成】C 69.37% H 6.22% N 5.52% O 18.9%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XII)

The crossed aldol condensation of 7-iodo-2,3-dihydro-1H-indol-2-one (VIII) with the chiral oxazolidine-carbaldehyde (IX) by means of LDA in THF gives a mixture of (Z)-(X) and (E)-(XI) isomers, which is isomerized to the desired (E)-(XI) compound by treatment with I2 . The condensation of (XI) with the borinated tyrosine intermediate (VII) catalyzed with PdCl2(dppf)2 yields the diaryl compound (XII), whose ester group is hydrolyzed with LiOH in THF/water to afford the carboxylic acid (XIII). The condensation of (XIII) with L-asparagine tert-butyl ester (XIV) by means of EDC and 1-hydroxy-7-azabenzotriazole (HOAt) in THF provides adduct (XV), which is oxidized with OsO4, NMO and 1,4-bis(9-O-dihydroquinidinine)phthalazine ((DHOD)2PHAL) in tert-butanol/water to give the glycol (XVI). The cleavage of the oxazolidine ring of (XVI) by means of pyridinium p-toluenesulfonate (PPTS) yields the trihydroxy compound (XVII).

1 Lin, S.N.; Danishefsky, S.J.; The total synthesis of proteasome inhibitors TMC-95A and TMC-95B: Discovery of a new method to generate cis-propenyl amides. Angew Chem. Int Ed 2002, 41, 3, 512.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VII) 53343 methyl (2S)-2-{[(benzyloxy)carbonyl]amino}-3-[4-(benzyloxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoate n/a C31H36BNO7 详情 详情
(VIII) 53344 7-iodo-1,3-dihydro-2H-indol-2-one n/a C8H6INO 详情 详情
(IX) 53345 tert-butyl (4R)-4-formyl-2,2-dimethyl-1,3-oxazolidine-3-carboxylate n/a C11H19NO4 详情 详情
(X) 53346 tert-butyl (4S)-4-[(7-iodo-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate n/a C19H23IN2O4 详情 详情
(XI) 53348 tert-butyl (4S)-4-[(7-iodo-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate n/a C19H23IN2O4 详情 详情
(XII) 53347 tert-butyl (4S)-4-({7-[2-(benzyloxy)-5-((2S)-2-{[(benzyloxy)carbonyl]amino}-3-methoxy-3-oxopropyl)phenyl]-2-oxo-1,2-dihydro-3H-indol-3-ylidene}methyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate n/a C44H47N3O9 详情 详情
(XIII) 53349 (2S)-3-[4-(benzyloxy)-3-(3-{(E)-[(4S)-3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidin-4-yl]methylidene}-2-oxo-2,3-dihydro-1H-indol-7-yl)phenyl]-2-{[(benzyloxy)carbonyl]amino}propanoic acid n/a C43H45N3O9 详情 详情
(XIV) 53350 tert-butyl (2S)-2,4-diamino-4-oxobutanoate 63094-81-5(盐酸盐) C8H16N2O3 详情 详情
(XV) 53351 tert-butyl (4S)-4-({7-[5-((2S)-3-{[(1S)-3-amino-1-(tert-butoxycarbonyl)-3-oxopropyl]amino}-2-{[(benzyloxy)carbonyl]amino}-3-oxopropyl)-2-(benzyloxy)phenyl]-2-oxo-1,2-dihydro-3H-indol-3-ylidene}methyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate n/a C51H59N5O11 详情 详情
(XVI) 53352 tert-butyl (4R)-4-[(R)-{(3S)-7-[5-((2S)-3-{[(1S)-3-amino-1-(tert-butoxycarbonyl)-3-oxopropyl]amino}-2-{[(benzyloxy)carbonyl]amino}-3-oxopropyl)-2-(benzyloxy)phenyl]-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl}(hydroxy)methyl]-2,2-dimethyl-1,3-oxazolid n/a C51H61N5O13 详情 详情
(XVII) 53353 tert-butyl (2S)-4-amino-2-[((2S)-3-[4-(benzyloxy)-3-((3S)-3-{(1R,2R)-2-[(tert-butoxycarbonyl)amino]-1,3-dihydroxypropyl}-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-7-yl)phenyl]-2-{[(benzyloxy)carbonyl]amino}propanoyl)amino]-4-oxobutanoate n/a C48H57N5O13 详情 详情

合成路线2

该中间体在本合成路线中的序号:(XII)

The crossed aldol condensation of 7-iodo-2,3-dihydro-1H-indol-2-one (VIII) with the chiral oxazolidine-carbaldehyde (IX) by means of LDA in THF gives a mixture of (Z)-(X) and (E)-(XI) isomers, which is isomerized to the desired (E)-(XI) compound by treatment with I2 . The condensation of (XI) with the borinated tyrosine intermediate (VII) catalyzed with PdCl2(dppf)2 yields the diaryl compound (XII), whose ester group is hydrolyzed with LiOH in THF/water to afford the carboxylic acid (XIII). The condensation of (XIII) with L-asparagine tert-butyl ester (XIV) by means of EDC and 1-hydroxy-7-azabenzotriazole (HOAt) in THF provides adduct (XV), which is oxidized with OsO4, NMO and 1,4-bis(9-O-dihydroquinidinine)phthalazine ((DHOD)2PHAL) in tert-butanol/water to give the glycol (XVI). The cleavage of the oxazolidine ring of (XVI) by means of pyridinium p-toluenesulfonate (PPTS) yields the trihydroxy compound (XVII).

1 Lin, S.N.; Danishefsky, S.J.; The total synthesis of proteasome inhibitors TMC-95A and TMC-95B: Discovery of a new method to generate cis-propenyl amides. Angew Chem. Int Ed 2002, 41, 3, 512.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VII) 53343 methyl (2S)-2-{[(benzyloxy)carbonyl]amino}-3-[4-(benzyloxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoate n/a C31H36BNO7 详情 详情
(VIII) 53344 7-iodo-1,3-dihydro-2H-indol-2-one n/a C8H6INO 详情 详情
(IX) 53345 tert-butyl (4R)-4-formyl-2,2-dimethyl-1,3-oxazolidine-3-carboxylate n/a C11H19NO4 详情 详情
(X) 53346 tert-butyl (4S)-4-[(7-iodo-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate n/a C19H23IN2O4 详情 详情
(XI) 53348 tert-butyl (4S)-4-[(7-iodo-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate n/a C19H23IN2O4 详情 详情
(XII) 53347 tert-butyl (4S)-4-({7-[2-(benzyloxy)-5-((2S)-2-{[(benzyloxy)carbonyl]amino}-3-methoxy-3-oxopropyl)phenyl]-2-oxo-1,2-dihydro-3H-indol-3-ylidene}methyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate n/a C44H47N3O9 详情 详情
(XIII) 53349 (2S)-3-[4-(benzyloxy)-3-(3-{(E)-[(4S)-3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidin-4-yl]methylidene}-2-oxo-2,3-dihydro-1H-indol-7-yl)phenyl]-2-{[(benzyloxy)carbonyl]amino}propanoic acid n/a C43H45N3O9 详情 详情
(XIV) 53350 tert-butyl (2S)-2,4-diamino-4-oxobutanoate 63094-81-5(盐酸盐) C8H16N2O3 详情 详情
(XV) 53351 tert-butyl (4S)-4-({7-[5-((2S)-3-{[(1S)-3-amino-1-(tert-butoxycarbonyl)-3-oxopropyl]amino}-2-{[(benzyloxy)carbonyl]amino}-3-oxopropyl)-2-(benzyloxy)phenyl]-2-oxo-1,2-dihydro-3H-indol-3-ylidene}methyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate n/a C51H59N5O11 详情 详情
(XVI) 53352 tert-butyl (4R)-4-[(R)-{(3S)-7-[5-((2S)-3-{[(1S)-3-amino-1-(tert-butoxycarbonyl)-3-oxopropyl]amino}-2-{[(benzyloxy)carbonyl]amino}-3-oxopropyl)-2-(benzyloxy)phenyl]-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl}(hydroxy)methyl]-2,2-dimethyl-1,3-oxazolid n/a C51H61N5O13 详情 详情
(XVII) 53353 tert-butyl (2S)-4-amino-2-[((2S)-3-[4-(benzyloxy)-3-((3S)-3-{(1R,2R)-2-[(tert-butoxycarbonyl)amino]-1,3-dihydroxypropyl}-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-7-yl)phenyl]-2-{[(benzyloxy)carbonyl]amino}propanoyl)amino]-4-oxobutanoate n/a C48H57N5O13 详情 详情
Extended Information