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

HRID 1874830Notes

Reaction equation

HRID 1874830 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:50]=[C:51]2[C:55](=[CH:56][CH:57]=1)[NH:54][C:53]([C:58](O)=[O:59])=[CH:52]2)(=[O:47])[CH3:46].CCN(C(C)C)C(C)C>CN(C=O)C>[C:45]([NH:48][C:49]1[CH:50]=[C:51]2[C:55](=[CH:56][CH:57]=1)[NH:54][C:53]([C:58]([NH:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([O:34][C:35]3[CH:36]=[C:37]([C:38]#[N:39])[CH:40]=[C:41]([Cl:43])[CH:42]=3)[C:28]=1[F:44])=[O:59])=[CH:52]2)(=[O:47])[CH3:46]

Participants

6

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 107751705-acetamido-1H-indole-2-carboxylic AcidHCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile

Product 1

HCID 594515125-(Acetylamino)-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamideYield 43%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (0.023 g, 0.062 mmol) was added to a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.013 g, 0.041 mmol), 5-(acetylamino)-1H-indole-2-carboxylic acid (0.009 g, 0.041 mmol) and DIPEA (0.011 mL, 0.062 mmol) in DMF (0.5 mL). The reaction mixture was stirred at RT overnight and was extracted with ethyl acetate and water. The organic layer was washed with brine, dried over sodium sulfate and concentrated. The residue was triturated with methanol to give the title compound (0.009 g, 43%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.50 (s, 1H), 9.74 (s, 1H), 8.95 (s, 1H), 7.91 (s, 1H), 7.78 (s, 1H), 7.40-7.49 (m, 3H), 7.32-7.40 (m, 1H), 7.28 (s, 1H), 7.15-7.24 (m, 1H), 7.06 (s, 1H), 4.53 (s, 2H), 1.98 (s, 3H). MS: m/z 511 (M+1).

Workup

  1. extractionwas extracted with ethyl acetate and water
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was triturated with methanol

Sources & evidence

ORD record
ord-eb61922c2623432b8b9b9ad6e712411a
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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