Ethyl Acetate → 4-Chloro-6-(4-cyclobutylpiperazin-1-yl)pyrimidine

HRID 2039474노트

반응식

HRID 2039474 반응식
Cl.Cl.[CH:3]1([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4]1.C(N(C(C)C)C(C)C)C.[Cl:22][C:23]1[CH:28]=[C:27](Cl)[N:26]=[CH:25][N:24]=1.C(OCC)(=O)C>O>[Cl:22][C:23]1[CH:28]=[C:27]([N:10]2[CH2:11][CH2:12][N:7]([CH:3]3[CH2:6][CH2:5][CH2:4]3)[CH2:8][CH2:9]2)[N:26]=[CH:25][N:24]=1

참가 물질

6

반응물 4

HCID 8857Ethyl AcetateHCID 709434,6-DichloropyrimidineHCID 81531DiisopropylethylamineHCID 451567991-Cyclobutylpiperazine dihydrochloride

생성물 1

HCID 579250694-Chloro-6-(4-cyclobutylpiperazin-1-yl)pyrimidine

시약·촉매·용매 1

HCID 962Water용매

실험 절차

1.8 g (8.4 mmol) of 1-cyclobutylpiperazine dihydrochloride (Zaragoza et al., J. Med. Chem. 2004, 47, 2833) are initially charged in 18 ml of water, and 2.9 ml (2.1 g, 16.9 mmol) of N-ethyl-N-(propan-2-yl)propane-2-amine are added. The mixture is stirred at RT for 30 min, and 1.3 g (8.4 mmol) of 4,6-dichloropyrimidine are added. The reaction mixture is stirred at 115° C. for 1 h and cooled to RT, 25 ml of ethyl acetate are added and the mixture is extracted with 25 ml of a saturated aqueous sodium bicarbonate solution. The organic phase is separated off, dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude product is purified by column chromatography on silica gel (mobile phase: dichloromethane/methanol 100/3). Yield: 1.9 g (89% of theory)

후처리

  1. stirringThe reaction mixture is stirred at 115° C. for 1 h
  2. temperaturecooled to RT
  3. extractionthe mixture is extracted with 25 ml of a saturated aqueous sodium bicarbonate solution
  4. customThe organic phase is separated off
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product is purified by column chromatography on silica gel (mobile phase: dichloromethane/methanol 100/3)

출처 및 근거

ORD 기록
ord-2545bbcfed6d4309aa083379f94461a5
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08580778B2

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