Diisopropylethylamine → 6-Chloro-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide

HRID 1874815Notes

Reaction equation

HRID 1874815 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:25][CH2:26][C:27]1[C:28]([F:44])=[C:29]([O:34][C:35]2[CH:36]=[C:37]([CH:40]=[C:41]([Cl:43])[CH:42]=2)[C:38]#[N:39])[C:30]([Cl:33])=[CH:31][CH:32]=1.[Cl:45][C:46]1[CH:54]=[C:53]2[C:49]([CH:50]=[C:51]([C:55](O)=[O:56])[NH:52]2)=[CH:48][CH:47]=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C.O>[Cl:45][C:46]1[CH:54]=[C:53]2[C:49]([CH:50]=[C:51]([C:55]([NH:25][CH2:26][C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([O:34][C:35]4[CH:36]=[C:37]([C:38]#[N:39])[CH:40]=[C:41]([Cl:43])[CH:42]=4)[C:28]=3[F:44])=[O:56])[NH:52]2)=[CH:48][CH:47]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 855846-Chloro-1H-indole-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile

Product 1

HCID 594516116-Chloro-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamideYield 42.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

HATU (91 mg, 0.24 mmol) was added to a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.050 g, 0.16 mmol), 6-chloro-1H-indole-2-carboxylic acid (0.050 g, 0.24 mmol) and DIPEA (0.042 ml, 0.24 mmol) in DMF (1.5 mL). After 1 h, the reaction mixture was diluted with ethyl acetate and water. The organic layer was separated, dried over sodium sulfate and concentrated. The residue was purified by column chromatography (hexane/EtOAc) to give the title compound (0.033 g, 42%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.76 (s, 1H), 9.09 (t, 1H), 7.81 (s, 1H), 7.64 (d, 1H), 7.45-7.54 (m, 3H), 7.36-7.44 (m, 2H), 7.19 (s, 1H), 7.04 (dd, 1H), 4.56 (d, 2H). MS: m/z 488 (M+1).

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by column chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-b33f822ff9ea41689a40c6cad7531847
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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