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4,6-Dichloro-5-methylpyrimidine → (1,1-Dimethylethyl)-3-[(6-chloro-5-methyl-4-pyrimidinyl)amino]-n-[(phenylmethoxy)carbonyl]alaninate

HRID 729741
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HRID 729741 반응식
Cl[C:2]1[C:7]([CH3:8])=[C:6]([Cl:9])[N:5]=[CH:4][N:3]=1.[NH2:10][CH2:11][C@@H:12]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[NH:13][C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15]>CN(C)C=O.C(N(C(C)C)CC)(C)C>[CH3:30][C:27]([O:26][C:24](=[O:25])[C@H:12]([CH2:11][NH:10][C:2]1[C:7]([CH3:8])=[C:6]([Cl:9])[N:5]=[CH:4][N:3]=1)[NH:13][C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])([CH3:28])[CH3:29]
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참가 물질

5

반응물 2

HCID 8188604,6-Dichloro-5-methylpyrimidineHCID 10803731(S)-tert-Butyl 3-amino-2-(((benzyloxy)carbonyl)amino)propanoate

생성물 1

HCID 12094347(1,1-Dimethylethyl)-3-[(6-chloro-5-methyl-4-pyrimidinyl)amino]-n-[(phenylmethoxy)carbonyl]alaninate수율 53.5%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 81531Diisopropylethylamine
용매

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온도
120 °C

실험 절차

A mixture of 325 mg (2 mmoles) of 4,6-dichloro-5-methyl-pyrimidine (marketed by SPECS), 600 mg (2 mmoles) of (1,1-dimethylethyl) 3-amino-N-[(phenylmethoxy)carbonyl]alaninate (prepared according to J. Med. Chem. (2001), 44(8), 1158-1176) in 3 ml of dimethylformamide and 3 ml of diisopropylethylamine is heated at 120° C. overnight. The reaction medium is concentrated to dryness under vacuum and the residue is taken up in a mixture of water, ethyl acetate and a saturated solution of sodium bicarbonate. The organic phase is separated and the aqueous phase reextracted with ethyl acetate. The combined organic phases are dried over magnesium sulphate then the solvent is evaporated off under vacuum. The residue is chromatographed on silicagel eluting with a gradient of heptane (100%) to a mixture of heptane-ethyl acetate (50-50). 450 mg (Yield=53%) of expected product is obtained in the form of an oil.

후처리

  1. concentrationThe reaction medium is concentrated to dryness under vacuum
  2. additionthe residue is taken up in a mixture of water, ethyl acetate
  3. customThe organic phase is separated
  4. dry with materialThe combined organic phases are dried over magnesium sulphate
  5. customthe solvent is evaporated off under vacuum
  6. customThe residue is chromatographed
  7. washon silicagel eluting with a gradient of heptane (100%) to a mixture of heptane-ethyl acetate (50-50)

출처 및 근거

ORD 기록
ord-3207d05f12e64c47b2f66cebb0dd7991
출처 데이터셋
uspto-grants-2009_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07582640B2

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