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

HRID 60078
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[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]
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참가 물질

7

반응물 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, 화합물

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-f6e88cbe65874830a2c42c189bab890c
출처 데이터셋
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09440957B2

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