Ammonia → 2,3-dihydro-5-(6-chloro-4-pyrimidinyloxy)-N-[4-(4-morpholinyl)-3-(trifluoromethyl)phenyl]-1H-indole-1-carboxamide

HRID 2264562

反応式

HRID 2264562 の反応式
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.C(N(CC)CC)C.Cl[C:26]([O:29]C(=O)OC(Cl)(Cl)Cl)(Cl)Cl.[Cl:37][C:38]1[N:43]=[CH:42][N:41]=[C:40]([O:44][C:45]2[CH:46]=[C:47]3[C:51](=[CH:52][CH:53]=2)[NH:50][CH:49]=[CH:48]3)[CH:39]=1.N>C(Cl)Cl>[Cl:37][C:38]1[N:43]=[CH:42][N:41]=[C:40]([O:44][C:45]2[CH:46]=[C:47]3[C:51](=[CH:52][CH:53]=2)[N:50]([C:26]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([N:12]4[CH2:13][CH2:14][O:15][CH2:16][CH2:17]4)=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:7]=2)=[O:29])[CH2:49][CH2:48]3)[CH:39]=1

参加物

7

反応物 5

HCID 222AmmoniaHCID 8471Triethylamine2 回HCID 94429TriphosgeneHCID 27713294-Morpholino-3-(trifluoromethyl)anilineHCID 574551565-((6-Chloropyrimidin-4-yl)oxy)-1H-indole

生成物 1

HCID 866182902,3-dihydro-5-(6-chloro-4-pyrimidinyloxy)-N-[4-(4-morpholinyl)-3-(trifluoromethyl)phenyl]-1H-indole-1-carboxamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒3 回

実験手順

A solution containing 5-amino-2-(4-morpholinyl)benzotrifluoride (3.16 g, 12.8 mmol) and triethylamine (2.48 mL, 17.8 mmol) in CH2Cl2 (87 mL) is added dropwise to a stirred solution of bis(trichloromethyl)carbonate (1.26 g, 4.25 mmol) in CH2Cl2 (43 mL) at 0° C. After 30 min, a solution containing 5-[(6-chloro-4-pyrimidinyl)oxy]-1H-indole (Intermediate IVa; 3.48 g, 14 mmol) and triethylamine (1.96 mL, 14 mmol) in CH2Cl2 (52 mL) is added dropwise. After stirring for a further 15 min an aqueous solution of ammonia (100 mL of 2.5%) is added and the mixture is extracted with CH2Cl2. The combined extracts are washed with saturated aqueous NaCl, dried (K2CO3) and the solvent is evaporated off under reduced pressure to afford a crude product which is recrystallised from EtOH to give the title compound as a colourless crystalline solid: NMR (400 MHz; DMSO-d6) δ 2.11 (m, 4H), 3.20 (t, J=8.3 Hz, 2H), 3.68 (m, 4H), 4.16 (t, J=8.5 Hz, 2H), 6.96 (dd, J=8.6 Hz, J=2.5 Hz, 1H), 7.09 (d, J=1.5 Hz, 1H), 7.28 (s, 1H), 7.52 (d, J=8.6 Hz, 1H), 7.84 (dd, J=8.8 Hz, J=2.5 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H), 7.92 (d, J=2.3 Hz, 1H), 8.62 (s, 1H) and 8.77 (s, 1H).

後処理

  1. additionis added dropwise
  2. additionis added
  3. extractionthe mixture is extracted with CH2Cl2
  4. washThe combined extracts are washed with saturated aqueous NaCl
  5. dry with materialdried (K2CO3)
  6. customthe solvent is evaporated off under reduced pressure
  7. customto afford a crude product which
  8. customis recrystallised from EtOH

出典と根拠

ORDレコード
ord-b54b38ec739c438c85042e262559ab30
出典データセット
uspto-grants-2010_12
特許番号
US07855215B2

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