tert-butyl (4S)-4-[(7-iodo-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】53348

【品名】tert-butyl (4S)-4-[(7-iodo-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】C₁₉H₂₃IN₂O₄

【分子量】470.30717

【元素组成】C 48.52% H 4.93% I 26.98% N 5.96% O 13.61%

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：(XI)

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).

参考文献中间体

合成目标

【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：(XI)

参考文献中间体

合成目标

【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