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

HRID 2264562

Reaktionsgleichung

Reaktionsgleichung von HRID 2264562
[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

Komponenten

7

Edukt 5

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-b54b38ec739c438c85042e262559ab30
Quelldatensatz
uspto-grants-2010_12
Patentnummer
US07855215B2

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