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Sodium borohydride → N-(7-(3-fluoro-2-(hydroxymethyl)-6-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 468969
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HRID 468969 반응식
[BH4-].[Na+].[F:3][C:4]1[C:5]([CH:27]=[O:28])=[C:6]([C:11]2[CH:20]=[C:19]3[C:14]([CH:15]=[C:16]([NH:21][C:22]([CH:24]4[CH2:26][CH2:25]4)=[O:23])[N:17]=[CH:18]3)=[CH:13][CH:12]=2)[C:7]([CH3:10])=[CH:8][CH:9]=1>C1COCC1.C(OCC)(=O)C>[F:3][C:4]1[C:5]([CH2:27][OH:28])=[C:6]([C:11]2[CH:20]=[C:19]3[C:14]([CH:15]=[C:16]([NH:21][C:22]([CH:24]4[CH2:25][CH2:26]4)=[O:23])[N:17]=[CH:18]3)=[CH:13][CH:12]=2)[C:7]([CH3:10])=[CH:8][CH:9]=1
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5

반응물 2

HCID 4311764Sodium borohydrideHCID 86674986N-(7-(3-fluoro-2-formyl-6-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide

생성물 1

HCID 67976415N-(7-(3-fluoro-2-(hydroxymethyl)-6-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide수율 40.8%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
40 °C

실험 절차

Sodium borohydride (11 mg, 0.29 mmol) was added to a solution of N-[7-(3-fluoro-2-formyl-6-methyl-phenyl)-3-isoquinolyl]cyclopropanecarboxamide (50 mg, 0.14 mmol) in THF (1 mL). The reaction mixture was heated at 40° C. for 1 hour and then diluted with ethyl acetate (40 mL) and washed with water (40 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo to provide a residue that was purified by reverse phase HPLC (5-85% acetonitrile in water w/0.1% NH4OH, 14 minutes). Desired fractions were combined and evaporated in vacuo to afford the title compound as an off-white solid (20 mg, 40%). 1H NMR (400 MHz, DMSO) δ 10.90 (s, 1H), 9.14 (s, 1H), 8.50 (s, 1H), 7.92 (d, J=8.5 Hz, 1H), 7.89 (s, 1H), 7.54 (dd, J=8.5, 1.4 Hz, 1H), 7.31 (dd, J=8.3, 5.8 Hz, 1H), 7.20-7.12 (m, 1H), 4.79 (t, J=4.9 Hz, 1H), 4.25-4.10 (m, 2H), 2.13-2.03 (m, 1H), 1.99 (s, 3H), 0.91-0.79 (m, 4H). LCMS (Method E): RT=4.648 min, M+H+=351.2.

후처리

  1. washwashed with water (40 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide a residue that
  7. customwas purified by reverse phase HPLC (5-85% acetonitrile in water w/0.1% NH4OH, 14 minutes)
  8. customevaporated in vacuo

출처 및 근거

ORD 기록
ord-72cc20457f7f4c3fb6ef1246a6e0e36a
출처 데이터셋
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08623889B2

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