Ammonium Chloride → (R)-1-(1-acryloylpiperidin-3-yl)-2-(3-(trifluoromethyl)benzamido)-1H-benzo[d]imidazole-5-carboxamide

HRID 60078Notes

Reaction equation

HRID 60078 reaction equation
[C:1]([N:5]1[CH2:10][CH2:9][CH2:8][C@@H:7]([N:11]2[C:15]3[CH:16]=[CH:17][C:18]([C:20](O)=[O:21])=[CH:19][C:14]=3[N:13]=[C:12]2[NH:23][C:24](=[O:35])[C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=2)[CH2:6]1)(=[O:4])[CH:2]=[CH2:3].[NH4+].[Cl-].OC1C2N=N[NH:44]C=2C=CC=1.Cl.C(N=C=NCCCN(C)C)C>CN(C=O)C.O>[C:1]([N:5]1[CH2:10][CH2:9][CH2:8][C@@H:7]([N:11]2[C:15]3[CH:16]=[CH:17][C:18]([C:20]([NH2:44])=[O:21])=[CH:19][C:14]=3[N:13]=[C:12]2[NH:23][C:24](=[O:35])[C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:32])([F:34])[F:33])[CH:26]=2)[CH2:6]1)(=[O:4])[CH:2]=[CH2:3]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 72704604(R)-1-(1-acryloylpiperidin-3-yl)-2-(3-(trifluoromethyl)benzamido)-1H-benzo[d]imidazole-5-carboxylic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 72704606(R)-1-(1-acryloylpiperidin-3-yl)-2-(3-(trifluoromethyl)benzamido)-1H-benzo[d]imidazole-5-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of Example 18 (50 mg, 0.1 mmol) and NH4Cl (7 mg, 0.11 mmol) in DMF (4 mL) were added hydroxybenzotriazole (15 mg, 0.11 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (21 mg, 0.11 mmol) and the mixture was stirred at room temperature for 14 h (completion of reaction monitored by TLC). The mixture was diluted with water and extracted with CH2Cl2 (3×20 mL). The combined organic phase was washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure. The crude material was purified by column chromatography (10% MeOH in CH2Cl2) to afford the title compound (Example 19). 1H-NMR (400 MHz, DMSO-d6): ∂ 13.0 (br s, 1H), 8.47 (d, J=7.2 Hz, 2H), 8.06-7.73 (m, 6H), 7.35 (s, 1H), 6.92-6.79 (m, 1H), 6.17-6.13 (m, 1H), 5.75-5.60 (m, 1H), 4.81-4.60 (m, 2H), 4.29-4.10 (m, 1H), 2.84-2.72 (m, 1H), 2.17-1.94 (m, 3H), 1.65 (s, 2H); MS calculated for C24H23F3N5O3 (M+H+) 486.17. found 486.3.

Workup

  1. custom(completion of reaction monitored by TLC)
  2. extractionextracted with CH2Cl2 (3×20 mL)
  3. washThe combined organic phase was washed with water and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified by column chromatography (10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-f6e88cbe65874830a2c42c189bab890c
Source dataset
uspto-grants-2016_09
Patent number
US09440957B2

Reaction notes

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