Ethanol → HCID 118005945, compound

HRID 1507322Notes

Reaction equation

HRID 1507322 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH:12]([C:14]3[C:15]([CH3:21])=[N:16][C:17]([CH3:20])=[CH:18][CH:19]=3)[OH:13])[CH:10]=2)[N:5]=[C:4]([O:22][CH3:23])[C:3]=1[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=1.CCO>[Pd].CCN(CC)CC>[CH3:21][C:15]1[C:14]([CH:12]([C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[N:5]=[C:4]([O:22][CH3:23])[C:3]([CH2:24][C:25]2[CH:26]=[CH:27][C:28]([C:31]([F:34])([F:32])[F:33])=[CH:29][CH:30]=2)=[CH:2]3)[OH:13])=[CH:19][CH:18]=[C:17]([CH3:20])[N:16]=1

Participants

5

Reactant 2

HCID 702EthanolHCID 86715629(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanol

Product 1

HCID 118005945HCID 118005945, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8471TriethylamineSolvent

Procedure

A 250 mL Parr flask containing (4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanol (155 mg, 0.32 mmol, Example 14a) was added EtOH (25 mL) and Et3N (1 mL) followed by 5% palladium on carbon (75 mg). The flask was pressurized to 50 psi with H2 gas and shaken for 18 hours. HPLC analysis indicated the conversion was approximately 40%. The reaction mixture was filtered through Celite® and concentrated. The residue was dissolved in MeOH and run in the H-cube hydrogenation apparatus using a 10% Pd/C cartridge at 50° C., 70 psi H2 and 1.2 ml/minute (all with closed loop recycling). After the cycling was complete, the solution was concentrated to dryness and the residue was chromatographed on silica gel (10% EtOAc-DCM increasing to 5% MeOH-DCM) to provide the title compound as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 7.76 (d, J=8.5 Hz, 1H), 7.58-7.47 (m, 3H), 7.40-7.31 (m, 3H), 7.30-7.20 (m, 2H), 6.94 (d, J=7.7 Hz, 1H), 4.05 (overlapping s, 6H), 2.51 (s, 3H), 2.45 (s, 3H). MS (ESI): mass calcd. for C26H23F3N2O2, 452.2, m/z found 453.2 [M+H]+.

Workup

  1. filtrationThe reaction mixture was filtered through Celite®
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in MeOH
  4. customat 50° C.
  5. custom70 psi H2 and 1.2 ml/minute (all with closed loop recycling)
  6. concentrationthe solution was concentrated to dryness
  7. customthe residue was chromatographed on silica gel (10% EtOAc-DCM increasing to 5% MeOH-DCM)

Sources & evidence

ORD record
ord-a6e82a7145dc46c6973598e975fbef1b
Source dataset
uspto-grants-2015_12
Patent number
US09221804B2

Reaction notes

Loading…