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

HRID 1502485Notes

Reaction equation

HRID 1502485 reaction equation
[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

Participants

5

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-9c89d079900a4e0e94b93c42ae1e0eb7
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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