Methanol → HCID 131735019, compound

HRID 926620Notes

Reaction equation

HRID 926620 reaction equation
[CH2:1]([C:8]1[C:9]([C:33]([F:36])([F:35])[F:34])=[N:10][C:11]2[C:16]([C:17]=1Cl)=[CH:15][C:14]([C:19]([C:27]1[N:31]([CH3:32])[CH:30]=[N:29][CH:28]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1)[OH:20])=[CH:13][CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:37]([OH:43])([C:39]([F:42])([F:41])[F:40])=[O:38].C[O-].[Na+].CO>>[CH2:1]([C:8]1[C:9]([C:33]([F:36])([F:35])[F:34])=[N:10][C:11]2[C:16]([C:17]=1[O:38][CH3:37])=[CH:15][C:14]([C:19]([C:27]1[N:31]([CH3:32])[CH:30]=[N:29][CH:28]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1)[OH:20])=[CH:13][CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:37]([OH:43])([C:39]([F:42])([F:41])[F:40])=[O:38]

Participants

4

Reactant 3

HCID 887MethanolHCID 10942334Sodium MethoxideHCID 131735020HCID 131735020, compound

Product 1

HCID 131735019HCID 131735019, compound

Conditions

Temperature
82 °C

Procedure

A mixture of (3-benzyl-4-chloro-2-(trifluoromethyl)quinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(pyridin-2-yl)methanol•TFA (84 mg, 0.11 mmol, Example 97) and 0.5 M NaOMe in MeOH (0.80 mL, 0.40 mmol) in a sealed tube was heated at 82° C. for 24 hours. The solvent was evaporated, and the residue was partitioned between EtOAc and water. The organic layer was dried over Na2SO4, filtered, and concentrated. The crude was purified by reverse phase HPLC (water/acetonitrile/0.1% TFA) to provide the title compound as a white solid. 1H NMR (400 MHz, CD3OD) δ 8.96 (s, 1H), 8.61 (d, J=4.04 Hz, 1H), 8.28 (d, J=2.02 Hz, 1H), 8.20 (d, J=9.09 Hz, 1H), 8.00 (dd, J=2.02, 9.09 Hz, 1H), 7.96 (dd, J=2.02, 8.08 Hz, 1H), 7.80 (d, J=8.08 Hz, 1H), 7.39-7.45 (m, 1H), 7.19-7.26 (m, 2H), 7.12-7.18 (m, 1H), 7.09 (d, J=2.02 Hz, 1H), 7.06 (d, J=7.07 Hz, 2H), 4.36 (s, 2H), 3.78 (s, 3H), 3.63 (s, 3H); MS m/e 505.0 [M+H]+.

Workup

  1. customThe solvent was evaporated
  2. customthe residue was partitioned between EtOAc and water
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude was purified by reverse phase HPLC (water/acetonitrile/0.1% TFA)

Sources & evidence

ORD record
ord-b554d711109a486db1e0cdfa9eacfe99
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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