Ammonia → Trifluoroacetic acid

HRID 926628Notes

Reaction equation

HRID 926628 reaction equation
[CH2:1]([C:8]1[C:9]([O:37][CH3:38])=[N:10][C:11]2[C:16]([C:17]=1[Cl:18])=[CH:15][C:14]([C:19]([C:31]1[N:35]([CH3:36])[CH:34]=[N:33][CH:32]=1)([C:21]1[CH:22]=[N:23][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:26]=1)O)=[CH:13][CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:39]([OH:45])([C:41]([F:44])([F:43])[F:42])=[O:40].[H-].[Na+].C(OC(=O)C)(=O)C.[NH3:55]>CN(C=O)C>[CH2:1]([C:8]1[C:9]([O:37][CH3:38])=[N:10][C:11]2[C:16]([C:17]=1[Cl:18])=[CH:15][C:14]([C:19]([C:31]1[N:35]([CH3:36])[CH:34]=[N:33][CH:32]=1)([C:21]1[CH:22]=[N:23][C:24]([C:27]([F:28])([F:29])[F:30])=[CH:25][CH:26]=1)[NH2:55])=[CH:13][CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:39]([OH:45])([C:41]([F:44])([F:43])[F:42])=[O:40].[C:39]([OH:45])([C:41]([F:44])([F:43])[F:42])=[O:40]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 7918Acetic AnhydrideHCID 24758Sodium hydrideHCID 131735024HCID 131735024, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 131735028HCID 131735028, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (3-benzyl-4-chloro-2-methoxyquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol (446 mg, 0.830 mmol, Example 110) and DMF (15 mL) was added NaH (60% in mineral oil, 90 mg, 2.3 mmol) at room temperature. After stirring for 15 minutes, acetic anhydride (0.16 mL, 1.7 mmol) was added. After stirring for 1 hour, NH3 (7.0 M in MeOH, 1.0 mL, 7.0 mmol) was added. The mixture was stirred overnight and concentrated in vacuo. The residue was partitioned between EtOAc and water. The organic layers were washed with water, and the aqueous layer was back extracted with EtOAc. The extracts were dried (Na2SO4), filtered, and concentrated. The residue was purified by reverse phase HPLC (water/acetonitrile/0.1% TFA) to afford the title compound as a TFA salt. 1H NMR (400 MHz, MeOH-d4) δ 8.97 (s, 1H), 8.77 (d, J=2.02 Hz, 1H), 8.11 (d, J=2.02 Hz, 1H), 8.00 (dd, J=2.27, 8.34 Hz, 1H), 7.94 (d, J=9.09 Hz, 1H), 7.88 (d, J=8.08 Hz, 1H), 7.62 (dd, J=2.27, 8.84 Hz, 1H), 7.20-7.24 (m, 4H), 7.12-7.18 (m, 1H), 6.94 (d, J=1.52 Hz, 1H), 4.30 (s, 2H), 4.08 (s, 3H), 3.72 (s, 3H); MS m/e 538.2 [M+H]+.

Workup

  1. stirringAfter stirring for 1 hour
  2. stirringThe mixture was stirred overnight
  3. concentrationconcentrated in vacuo
  4. customThe residue was partitioned between EtOAc and water
  5. washThe organic layers were washed with water
  6. extractionthe aqueous layer was back extracted with EtOAc
  7. dry with materialThe extracts were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by reverse phase HPLC (water/acetonitrile/0.1% TFA)

Sources & evidence

ORD record
ord-07bb05c48992495785cd772b353a3688
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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