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 1807754ノート

反応式

HRID 1807754 の反応式
[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]

参加物

6

反応物 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

生成物 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)urea収率 83.9%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
120 °C

実験手順

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]+

後処理

  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%)

出典と根拠

ORDレコード
ord-18109f56b1a0458cb43d6626a99f8f9e
出典データセット
uspto-grants-2013_01
特許番号
US08357679B2

反応ノート

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