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

HRID 729739노트

반응식

HRID 729739 반응식
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]

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
120 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-b6c00ad528bb43b2b4b438252c37308f
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07582640B2

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