Diisopropylethylamine → (1,1-dimethylethyl) 3-[(6-chloro-5-ethyl-4-pyrimidinyl)amino]-N-[(phenylmethoxy)carbonyl]alaninate

HRID 729739ノート

反応式

HRID 729739 の反応式
C(N(C(C)C)CC)(C)C.Cl[C:11]1[C:16]([CH2:17][CH3:18])=[C:15]([Cl:19])[N:14]=[CH:13][N:12]=1.[CH3:20][C:21]([O:24][C:25](=[O:40])[C@H:26]([CH2:38][NH2:39])[NH:27][C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29])([CH3:23])[CH3:22].C(=O)(O)[O-].[Na+]>CN(C)C=O.C(OCC)(=O)C.O>[CH3:23][C:21]([O:24][C:25](=[O:40])[C@H:26]([CH2:38][NH:39][C:11]1[C:16]([CH2:17][CH3:18])=[C:15]([Cl:19])[N:14]=[CH:13][N:12]=1)[NH:27][C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29])([CH3:20])[CH3:22]

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 10803731(S)-tert-Butyl 3-amino-2-(((benzyloxy)carbonyl)amino)propanoateHCID 218284324,6-Dichloro-5-ethylpyrimidine

生成物 1

HCID 12094339(1,1-dimethylethyl) 3-[(6-chloro-5-ethyl-4-pyrimidinyl)amino]-N-[(phenylmethoxy)carbonyl]alaninate収率 72%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
120 °C

実験手順

10 ml of diisopropylethylamine is added to a mixture of 3.8 g (21 mmoles) of 4,6-dichloro-5-ethyl-pyrimidine and 4.4 g (15 mmoles) of (1,1-dimethylethyl)3-amino-N-[(phenylmethoxy)carbonyl]alaninate (prepared according to J. Med. Chem. (2001), 44(8), 1158-1176) in 50 ml of dimethylformamide, then this mixture is heated at 120° C. for 6 hours. Then the dimethylformamide is eliminated under vacuum and the residue is taken up in a mixture of ethyl acetate, water and a saturated solution of sodium bicarbonate. The organic phase is decanted then dried over magnesium sulphate and the solvent is eliminated by evaporation under vacuum. The residue is chromatographed on silicagel eluting with a gradient of 100% heptane to heptane-ethyl acetate 50-50. 4.7 g (Yield=70%) of expected product is obtained in the form of an oil.

後処理

  1. customThe organic phase is decanted
  2. dry with materialthen dried over magnesium sulphate
  3. customthe solvent is eliminated by evaporation under vacuum
  4. customThe residue is chromatographed
  5. washon silicagel eluting with a gradient of 100% heptane to heptane-ethyl acetate 50-50

出典と根拠

ORDレコード
ord-b6c00ad528bb43b2b4b438252c37308f
出典データセット
uspto-grants-2009_09
特許番号
US07582640B2

反応ノート

読み込み中…