Methanol → HCID 86716146, compound

HRID 627567Notes

Reaction equation

HRID 627567 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([C:24]3[N:28]([CH3:29])[CH:27]=[N:26][CH:25]=3)([C:14]3[CH:15]=[N:16][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:19]=3)[OH:13])[CH:10]=2)[N:5]=[C:4]([C:30]([F:33])([F:32])[F:31])[C:3]=1[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[C:40]([OH:46])([C:42]([F:45])([F:44])[F:43])=[O:41].C[O-].[Na+].CO>>[CH3:40][O:41][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([C:24]3[N:28]([CH3:29])[CH:27]=[N:26][CH:25]=3)([C:14]3[CH:15]=[N:16][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:19]=3)[OH:13])[CH:10]=2)[N:5]=[C:4]([C:30]([F:33])([F:32])[F:31])[C:3]=1[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[C:40]([OH:46])([C:42]([F:45])([F:44])[F:43])=[O:41]

Participants

4

Reactant 3

HCID 887Methanol2×HCID 10942334Sodium Methoxide2×HCID 86716144HCID 86716144, compound

Product 1

HCID 86716146HCID 86716146, compound

Conditions

Temperature
70 °C

Procedure

A mixture of (4-chloro-3-phenyl-2-(trifluoromethyl)quinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol•TFA (78 mg, 0.099 mmol, Example 172) and 0.5 M NaOMe in MeOH (0.46 mL, 0.23 mmol) in a sealed tube was heated at 70° C. for 7 hours. More 0.5 M NaOMe in MeOH (0.33 mL, 0.17 mmol) was added and the mixture was heated at the same temperature for another hour. The solvent was evaporated, and DMSO was added. After filtering through a syringe filter, the filtrate was purified by reverse phase HPLC (water/acetonitrile/0.1% TFA) to give the title compound as a white solid. 1H NMR (400 MHz, MeOD-d4) δ 9.07 (s, 1H), 8.86 (d, J=2.02 Hz, 1H), 8.34 (d, J=2.53 Hz, 1H), 8.27 (d, J=8.59 Hz, 1H), 8.13 (dd, J=2.02, 8.08 Hz, 1H), 7.84-7.95 (m, 2H), 7.46-7.56 (m, 3H), 7.35-7.45 (m, 2H), 7.15 (s, 1H), 3.72 (s, 3H), 3.55 (s, 3H); MS m/e 559.2 [M+H]+.

Workup

  1. temperaturethe mixture was heated at the same temperature for another hour
  2. customThe solvent was evaporated
  3. additionDMSO was added
  4. filtrationAfter filtering through a syringe
  5. filtrationfilter
  6. customthe filtrate was purified by reverse phase HPLC (water/acetonitrile/0.1% TFA)

Sources & evidence

ORD record
ord-8b2b01d587cd46d8926527fb0fc35337
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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