Diisopropylethylamine → 6-acetamido-N-[[4-chloro-3-(3-chloro-5-cyanophenoxy)-2-fluorophenyl]methyl]-1H-indole-2-carboxamide

HRID 1874832Notes

Reaction equation

HRID 1874832 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.[C:45]([NH:48][C:49]1[CH:57]=[C:56]2[C:52]([CH:53]=[C:54]([C:58](O)=[O:59])[NH:55]2)=[CH:51][CH:50]=1)(=[O:47])[CH3:46].CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C.O>[C:45]([NH:48][C:49]1[CH:57]=[C:56]2[C:52]([CH:53]=[C:54]([C:58]([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:59])[NH:55]2)=[CH:51][CH:50]=1)(=[O:47])[CH3:46]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 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-chlorobenzonitrileHCID 594515286-(acetylamino)-1H-indole-2-carboxylic acid

Product 1

HCID 594513686-acetamido-N-[[4-chloro-3-(3-chloro-5-cyanophenoxy)-2-fluorophenyl]methyl]-1H-indole-2-carboxamideYield 31.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

HATU (0.086 g, 0.227 mmol) was added to a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.047 g, 0.151 mmol), 6-(acetylamino)-1H-indole-2-carboxylic acid (0.033 g, 0.151 mmol) and DIPEA (0.040 mL, 0.227 mmol) in DMF (1 mL). The mixture was stirred at RT for 2 h. The reaction mixture was diluted with ethyl acetate and water. The organic layer was washed with water and dried over sodium sulfate, and the solvent was evaporated. The resulting oil was triturated with methylene chloride:methanol. The resulting solid was collected by filtration and dried under vacuum to give the title compound (0.024 g, 31%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.46 (s, 1H), 9.85 (s, 1H), 9.01 (m, 1H), 7.91 (s, 1H), 7.80 (s, 1H), 7.40-7.53 (m, 4H), 7.35 (t, 1H), 7.11 (m, 2H), 4.51 (d, 2H), 2.00 (s, 3H). MS: m/z 511 (M+1).

Workup

  1. washThe organic layer was washed with water
  2. dry with materialdried over sodium sulfate
  3. customthe solvent was evaporated
  4. customThe resulting oil was triturated with methylene chloride
  5. filtrationThe resulting solid was collected by filtration
  6. customdried under vacuum

Sources & evidence

ORD record
ord-5347ad5473ab4068a56eb85e79767c30
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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