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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
ノート
印刷プレビュー

反応式

HRID 729741 の反応式
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]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 81531Diisopropylethylamine
溶媒

反応条件

温度
120 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-3207d05f12e64c47b2f66cebb0dd7991
出典データセット
uspto-grants-2009_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07582640B2

反応ノート

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