溴乙腈 → 6-Chloro-N-(cyanomethyl)-N-{(3S)-1-[(1S)-1-methyl-2-oxo-2-piperidin-1-ylethyl]-2-oxopyrrolidin-3-yl}naphthalene-2-sulfonamide

HRID 7315

反应方程式

HRID 7315 反应方程式
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([NH:15][C@H:16]1[CH2:20][CH2:19][N:18]([C@@H:21]([CH3:30])[C:22](=[O:29])[N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)[C:17]1=[O:31])(=[O:14])=[O:13])[CH:6]=[CH:5]2.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:43][C:44]#[N:45]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([N:15]([CH2:43][C:44]#[N:45])[C@H:16]1[CH2:20][CH2:19][N:18]([C@@H:21]([CH3:30])[C:22](=[O:29])[N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)[C:17]1=[O:31])(=[O:13])=[O:14])[CH:6]=[CH:5]2

参与物

5

反应物 3

HCID 11534溴乙腈HCID 2733832双三甲基硅基胺基锂2 次HCID 236461306-chloro-N-{(3S)-1-[(1S)-1-methyl-2-oxo-2-piperidin-1-ylethyl]-2-oxopyrrolidin-3-yl}naphthalene-2-sulfonamide

产物 1

HCID 865938636-Chloro-N-(cyanomethyl)-N-{(3S)-1-[(1S)-1-methyl-2-oxo-2-piperidin-1-ylethyl]-2-oxopyrrolidin-3-yl}naphthalene-2-sulfonamide收率 43%

试剂、催化剂与溶剂 1

HCID 8028四氢呋喃溶剂

反应条件

温度
-78 °C

实验过程

A solution of 6-chloro-N-{(3S)-1-[(1S)-1-methyl-2-oxo-2-piperidin-1-ylethyl]-2-oxopyrrolidin-3-yl}naphthalene-2-sulfonamide (0.015 g) in THF (2 ml) was cooled to −78° C. under nitrogen, and treated with lithium bis(trimethylsilyl) amide (1.0M solution in THF; 0.042 ml), followed by bromoacetonitrile (0.019 g). The resultant solution was allowed to reach room temperature and stirred for a further 16 h. The mixture was then cooled to −78° C. and further lithium bis(trimethylsilyl) amide (0.042 ml) added. After reaching room temperature, the reaction mixture was stirred for a further 18 h and then quenched by the addition of methanol (1 ml). The resultant solution was concentrated under reduced pressure and the residue partitioned between water and DCM. The organic layer was separated, dried (over magnesium sulphate) and concentrated under reduced pressure. The residue was purified by mass directed preparative h.p.l.c to give the title compound (0.007 g) as a colourless gum.

后处理

  1. customto reach room temperature
  2. customAfter reaching room temperature
  3. stirringthe reaction mixture was stirred for a further 18 h
  4. customquenched by the addition of methanol (1 ml)
  5. concentrationThe resultant solution was concentrated under reduced pressure
  6. customthe residue partitioned between water and DCM
  7. customThe organic layer was separated
  8. dry with materialdried (over magnesium sulphate)
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by mass

来源与证据

ORD记录
ord-df5abb0d36a745ff964e2f8fa27724ba
来源数据集
uspto-grants-2006_08
专利号
US07084139B2

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