Ozone → HCID 90408682, compound

HRID 2177651Notes

Reaction equation

HRID 2177651 reaction equation
[O:1]=[O+][O-].[Cl:4][C:5]1[C:31]([C:32]([F:35])([F:34])[F:33])=[CH:30][CH:29]=[CH:28][C:6]=1[C:7]([NH:9][CH:10]([C:12]1[N:13]=[N:14][N:15]([C:22]2[N:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[C:16]=1[CH2:17][CH:18]=C(C)C)[CH3:11])=[O:8].[BH4-].[Na+]>CO>[Cl:4][C:5]1[C:31]([C:32]([F:35])([F:34])[F:33])=[CH:30][CH:29]=[CH:28][C:6]=1[C:7]([NH:9][CH:10]([C:12]1[N:13]=[N:14][N:15]([C:22]2[N:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[C:16]=1[CH2:17][CH2:18][OH:1])[CH3:11])=[O:8]

Participants

5

Reactant 3

HCID 24823OzoneHCID 4311764Sodium borohydrideHCID 90409591HCID 90409591, compound

Product 1

HCID 90408682HCID 90408682, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A stream of O3 generated from an ozonator was passed though the solution of Intermediate 238 (200 mg, 0.43 mmol, 1.0 equiv.) in MeOH (30 mL) at −78° C. until the color of the reaction solution became blue (˜10 min). NaBH4 (49 mg, 1.3 mmol, 3.0 equiv.) was added at −78° C. The reaction solution was warmed to room temperature and partitioned between EtOAc and brine. The organic layer was separated, dried over Na2SO4 and concentrated. The crude product was purified by column chromatography with EtOAc/hexanes as eluents to afford the title compound (140 mg, 0.30 mmol, 70% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.95-8.88 (d, J=4.9 Hz, 2H), 7.81-7.73 (dd, J=7.8, 1.7 Hz, 1H), 7.67-7.58 (dd, J=7.7, 1.6 Hz, 1H), 7.50-7.44 (t, J=4.9 Hz, 1H), 7.43-7.36 (t, J=7.8 Hz, 1H), 6.95-6.83 (d, J=8.1 Hz, 1H), 5.62-5.44 (m, 1H), 4.06-3.89 (m, 2H), 3.66-3.56 (ddd, J=14.7, 6.1, 4.6 Hz, 1H), 3.44-3.34 (ddd, J=14.7, 7.7, 4.9 Hz, 1H), 3.20-3.14 (t, J=5.9 Hz, 1H), 1.88-1.71 (d, J=7.0 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 165.5, 159.0, 155.5, 147.4, 138.3, 133.1, 132.2, 129.2, 129.1 (q, JC—F=31.5 Hz), 128.5 (q, JC—F=5.2 Hz), 126.8, 122.5 (q, JC—F=273.4 Hz), 120.7, 61.1, 41.4, 27.3, 20.7. HRMS-ESI (m/z): [M+H]+ calcd for C18H17ClF3N6O2, 441.1048. found, 441.1038.

Workup

  1. custom(˜10 min)
  2. custompartitioned between EtOAc and brine
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography with EtOAc/hexanes as eluents

Sources & evidence

ORD record
ord-a21c6e26a7624240bf8ae7b51b00ff91
Source dataset
uspto-grants-2015_06
Patent number
US09066946B2

Reaction notes

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