4-Aminopyrimidine → 1-(2-Fluoro-4-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazine-1-carbonyl)phenyl)-3-(Pyrimidin-4-yl)urea

HRID 1807754노트

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HRID 1807754 반응식
[N:1]1[CH:6]=[CH:5][C:4]([NH2:7])=[N:3][CH:2]=1.C(N(C(C)C)C(C)C)C.ClC(Cl)(O[C:21](=[O:27])OC(Cl)(Cl)Cl)Cl.[NH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]([N:38]2[CH2:43][CH2:42][N:41]([CH2:44][C:45]3[CH:50]=[CH:49][C:48]([C:51]([O:60][Si](C(C)(C)C)(C)C)([C:56]([F:59])([F:58])[F:57])[C:52]([F:55])([F:54])[F:53])=[CH:47][CH:46]=3)[CH2:40][CH2:39]2)=[O:37])=[CH:32][C:31]=1[F:68]>ClCCl>[F:68][C:31]1[CH:32]=[C:33]([C:36]([N:38]2[CH2:39][CH2:40][N:41]([CH2:44][C:45]3[CH:50]=[CH:49][C:48]([C:51]([OH:60])([C:52]([F:53])([F:54])[F:55])[C:56]([F:58])([F:59])[F:57])=[CH:47][CH:46]=3)[CH2:42][CH2:43]2)=[O:37])[CH:34]=[CH:35][C:30]=1[NH:29][C:21]([NH:7][C:4]1[CH:5]=[CH:6][N:1]=[CH:2][N:3]=1)=[O:27]

참가 물질

6

반응물 4

HCID 689584-AminopyrimidineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 59175907(4-Amino-3-fluorophenyl)(4-(4-(2-(tert-butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazin-1-yl)methanone

생성물 1

HCID 445123941-(2-Fluoro-4-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazine-1-carbonyl)phenyl)-3-(Pyrimidin-4-yl)urea수율 83.9%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
120 °C

실험 절차

Pyrimidin-4-amine (0.337 mmol, 0.032 g) and N-ethyl-N-isopropylpropan-2-amine (1.145 mmol, 0.189 mL, 0.148 g) were stirred in dichloromethane (2 mL) at room temperature. Triphosgene (0.125 mmol, 0.037 g) was added and the reaction stirred for 30 minutes. (4-Amino-3-fluorophenyl)(4-(4-(2-(tert-butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazin-1-yl)methanone (0.168 mmol, 0.1 g) was added and the reaction heated to 120° C. in the microwave for 10 minutes. The reaction mixture was washed with water and concentrated under reduced pressure. The resulting residue was purified by silica column chromatography (eluant dichloromethane/methanol 0% to 5%) to afford the title compound (63 mg). MS (ESI) m/z 715.7 [M+H]+

후처리

  1. washThe reaction mixture was washed with water
  2. concentrationconcentrated under reduced pressure
  3. customThe resulting residue was purified by silica column chromatography (eluant dichloromethane/methanol 0% to 5%)

출처 및 근거

ORD 기록
ord-18109f56b1a0458cb43d6626a99f8f9e
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08357679B2

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