di(tert-butyl) (2R,4R,5R)-5-{(1R)-1-(acetylamino)-2-[(triisopropylsilyl)oxy]ethyl}-4-(hydroxymethyl)-1,2-pyrrolidinedicarboxylate -Drug Synthesis Database

【结构式】

【分子编号】55145

【品名】di(tert-butyl) (2R,4R,5R)-5-{(1R)-1-(acetylamino)-2-[(triisopropylsilyl)oxy]ethyl}-4-(hydroxymethyl)-1,2-pyrrolidinedicarboxylate

【CA登记号】

【分子式】C₂₈H₅₄N₂O₇Si

【分子量】558.83154

【元素组成】C 60.18% H 9.74% N 5.01% O 20.04% Si 5.03%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XIII)

The mixture of amines (XI) was converted to the respective acetamides, and the desired isomer (XII) was then isolated by column chromatography. Hydrolysis of the acetate ester function of (XII) provided alcohol (XIII), which was oxidized to aldehyde (XIV) under Swern conditions. Wittig reaction of aldehyde (XIV) with ethyl triphenylphosphonium bromide and potassium tert-butoxide led to the (Z)-olefin (XV). After removal of the O-silyl protecting group of (XV) by means of tetrabutylammonium fluoride, the resultant alcohol (XVI) was oxidized to aldehyde (XVII) employing the Dess-Martin periodinane reagent. Addition of propylmagnesium bromide to aldehyde (XVII) furnished the alcohol adduct (XVIII).

参考文献中间体

合成目标

【1】 Inhibitors of neuraminidases. WO 0128996 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XI)	55143	di(tert-butyl) (2R,4R,5R)-4-[(acetyloxy)methyl]-5-{1-amino-2-[(triisopropylsilyl)oxy]ethyl}-1,2-pyrrolidinedicarboxylate	C₂₈H₅₄N₂O₇Si	详情	详情
(XII)	55144	di(tert-butyl) (2R,4R,5R)-5-{(1R)-1-(acetylamino)-2-[(triisopropylsilyl)oxy]ethyl}-4-[(acetyloxy)methyl]-1,2-pyrrolidinedicarboxylate	C₃₀H₅₆N₂O₈Si	详情	详情
(XIII)	55145	di(tert-butyl) (2R,4R,5R)-5-{(1R)-1-(acetylamino)-2-[(triisopropylsilyl)oxy]ethyl}-4-(hydroxymethyl)-1,2-pyrrolidinedicarboxylate	C₂₈H₅₄N₂O₇Si	详情	详情
(XIV)	55146	di(tert-butyl) (2R,4R,5R)-5-{(1R)-1-(acetylamino)-2-[(triisopropylsilyl)oxy]ethyl}-4-formyl-1,2-pyrrolidinedicarboxylate	C₂₈H₅₂N₂O₇Si	详情	详情
(XV)	55147	di(tert-butyl) (2R,4S,5R)-5-{(1R)-1-(acetylamino)-2-[(triisopropylsilyl)oxy]ethyl}-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate	C₃₀H₅₆N₂O₆Si	详情	详情
(XVI)	55148	di(tert-butyl) (2R,4S,5R)-5-[(1R)-1-(acetylamino)-2-hydroxyethyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate	C₂₁H₃₆N₂O₆	详情	详情
(XVII)	55149	di(tert-butyl) (2R,4S,5R)-5-[(1R)-1-(acetylamino)-2-oxoethyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate	C₂₁H₃₄N₂O₆	详情	详情
(XVIII)	55150	di(tert-butyl) (2R,4S,5R)-5-[(1R,2R)-1-(acetylamino)-2-hydroxypentyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate	C₂₄H₄₂N₂O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

参考文献中间体

合成目标

【1】 Inhibitors of neuraminidases. WO 0128996 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XI)	55143	di(tert-butyl) (2R,4R,5R)-4-[(acetyloxy)methyl]-5-{1-amino-2-[(triisopropylsilyl)oxy]ethyl}-1,2-pyrrolidinedicarboxylate	C₂₈H₅₄N₂O₇Si	详情	详情
(XII)	55144	di(tert-butyl) (2R,4R,5R)-5-{(1R)-1-(acetylamino)-2-[(triisopropylsilyl)oxy]ethyl}-4-[(acetyloxy)methyl]-1,2-pyrrolidinedicarboxylate	C₃₀H₅₆N₂O₈Si	详情	详情
(XIII)	55145	di(tert-butyl) (2R,4R,5R)-5-{(1R)-1-(acetylamino)-2-[(triisopropylsilyl)oxy]ethyl}-4-(hydroxymethyl)-1,2-pyrrolidinedicarboxylate	C₂₈H₅₄N₂O₇Si	详情	详情
(XIV)	55146	di(tert-butyl) (2R,4R,5R)-5-{(1R)-1-(acetylamino)-2-[(triisopropylsilyl)oxy]ethyl}-4-formyl-1,2-pyrrolidinedicarboxylate	C₂₈H₅₂N₂O₇Si	详情	详情
(XV)	55147	di(tert-butyl) (2R,4S,5R)-5-{(1R)-1-(acetylamino)-2-[(triisopropylsilyl)oxy]ethyl}-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate	C₃₀H₅₆N₂O₆Si	详情	详情
(XVI)	55148	di(tert-butyl) (2R,4S,5R)-5-[(1R)-1-(acetylamino)-2-hydroxyethyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate	C₂₁H₃₆N₂O₆	详情	详情
(XVII)	55149	di(tert-butyl) (2R,4S,5R)-5-[(1R)-1-(acetylamino)-2-oxoethyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate	C₂₁H₃₄N₂O₆	详情	详情
(XVIII)	55150	di(tert-butyl) (2R,4S,5R)-5-[(1R,2R)-1-(acetylamino)-2-hydroxypentyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate	C₂₄H₄₂N₂O₆	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XIII)

The mixture of amines (XI) was converted to the respective acetamides and the desired isomer (XII) was then isolated by column chromatography. Hydrolysis of the acetate ester function of (XII) provided alcohol (XIII), which was oxidized to aldehyde (XIV) under Swern conditions. Wittig reaction of aldehyde (XIV) with ethyl triphenylphosphonium bromide and potassium tert-butoxide led to the (Z)-olefin (XV). After removal of the O-silyl protecting group of (XV) by means of tetrabutylammonium fluoride, the resultant alcohol (XVI) was oxidized to aldehyde (XVII) employing the Dess-Martin periodinane reagent. Addition of propylmagnesium bromide to aldehyde (XVII) furnished the alcohol adduct (XVIII).

参考文献中间体

合成目标

【1】 Inhibitors of neuraminidases. WO 0128996 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XI)	55143	di(tert-butyl) (2R,4R,5R)-4-[(acetyloxy)methyl]-5-{1-amino-2-[(triisopropylsilyl)oxy]ethyl}-1,2-pyrrolidinedicarboxylate	C₂₈H₅₄N₂O₇Si	详情	详情
(XII)	55144	di(tert-butyl) (2R,4R,5R)-5-{(1R)-1-(acetylamino)-2-[(triisopropylsilyl)oxy]ethyl}-4-[(acetyloxy)methyl]-1,2-pyrrolidinedicarboxylate	C₃₀H₅₆N₂O₈Si	详情	详情
(XIII)	55145	di(tert-butyl) (2R,4R,5R)-5-{(1R)-1-(acetylamino)-2-[(triisopropylsilyl)oxy]ethyl}-4-(hydroxymethyl)-1,2-pyrrolidinedicarboxylate	C₂₈H₅₄N₂O₇Si	详情	详情
(XIV)	55146	di(tert-butyl) (2R,4R,5R)-5-{(1R)-1-(acetylamino)-2-[(triisopropylsilyl)oxy]ethyl}-4-formyl-1,2-pyrrolidinedicarboxylate	C₂₈H₅₂N₂O₇Si	详情	详情
(XV)	55147	di(tert-butyl) (2R,4S,5R)-5-{(1R)-1-(acetylamino)-2-[(triisopropylsilyl)oxy]ethyl}-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate	C₃₀H₅₆N₂O₆Si	详情	详情
(XVI)	55148	di(tert-butyl) (2R,4S,5R)-5-[(1R)-1-(acetylamino)-2-hydroxyethyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate	C₂₁H₃₆N₂O₆	详情	详情
(XVII)	55149	di(tert-butyl) (2R,4S,5R)-5-[(1R)-1-(acetylamino)-2-oxoethyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate	C₂₁H₃₄N₂O₆	详情	详情
(XVIII)	55150	di(tert-butyl) (2R,4S,5R)-5-[(1R,2R)-1-(acetylamino)-2-hydroxypentyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate	C₂₄H₄₂N₂O₆	详情	详情

Extended Information