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

HRID 2264562

반응식

HRID 2264562 반응식
[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

참가 물질

7

반응물 5

HCID 222AmmoniaHCID 8471Triethylamine2회HCID 94429TriphosgeneHCID 27713294-Morpholino-3-(trifluoromethyl)anilineHCID 574551565-((6-Chloropyrimidin-4-yl)oxy)-1H-indole

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매3회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-b54b38ec739c438c85042e262559ab30
출처 데이터셋
uspto-grants-2010_12
특허 번호
US07855215B2

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