LY3295668 → (S)-[2-[(1,1-dimethylethyl)amino]-2-oxo-1-(phenylmethyl)ethyl]-carbamic acid 1,1-dimethylethyl ester

HRID 278878

反应方程式

HRID 278878 反应方程式
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:25]([OH:27])=O)[CH2:10][C:11]1[CH:16]=[CH:15][C:14](OCC2C=CC=CC=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:28]([NH2:32])([CH3:31])([CH3:30])[CH3:29]>CN(C=O)C>[CH3:4][C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:25]([NH:32][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:27])([CH3:2])[CH3:3]

参与物

4

反应物 2

HCID 6385LY3295668HCID 98763Boc-O-苄基-L-酪氨酸

产物 1

HCID 11809380(S)-[2-[(1,1-dimethylethyl)amino]-2-oxo-1-(phenylmethyl)ethyl]-carbamic acid 1,1-dimethylethyl ester收率 153.7%

试剂、催化剂与溶剂 1

HCID 6228N,N-二甲基甲酰胺溶剂

反应条件

温度
0 °C

实验过程

A solution of N-(tert-butyloxycarbonyl)-O-benzyl-L-tyrosine (Bachem, 2.00 g, 5.38 mmol) in 20 mL of DMF was cooled to 0° C. and treated with iPr NEt (1.5 mL) followed by O-benzotriazol-1-yl-N,N,N′,N′-bis(tetramethylene)-uronium hexafluoro phosphate (2.04 g, 5.38 mmol, Novabiochem, La Jolla, Calif.). The resulting suspension was stirred for 30 minutes at 0° C. and then treated with tert-butylamine (0.48 g, 6.56 mmol). The reaction mixture was stirred for 1 hour at 0° C. and warmed to room temperature. The reaction mixture was poured into Et O and washed sequentially with saturated aqueous NaHCO3 solution, and saturated aqueous NaCl solution. The organic phase was dried (MgSO4), filtered, and concentrated. The crude residue was purified by chromatography (silica gel, 3:1 heptane/ethyl acetate) to give (S)-[2-[(1,1-dimethylethyl)amino]-2-oxo-1-(phenylmethyl)ethyl]-carbamic acid 1,1-dimethylethyl ester (2.65 g).

后处理

  1. stirringThe reaction mixture was stirred for 1 hour at 0° C.
  2. temperaturewarmed to room temperature
  3. additionThe reaction mixture was poured into Et O
  4. washwashed sequentially with saturated aqueous NaHCO3 solution, and saturated aqueous NaCl solution
  5. dry with materialThe organic phase was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by chromatography (silica gel, 3:1 heptane/ethyl acetate)

来源与证据

ORD记录
ord-962f5357127445a9b30f7e2e42ca3032
来源数据集
uspto-grants-2002_03
专利号
US06362174B1

关联笔记

加载中…