HCID 72203421, compound → HCID 72203420, compound

HRID 629083Notes

Reaction equation

HRID 629083 reaction equation
[O:1]1[CH2:6][CH:5]=[C:4]([C:7]2[C:26]([C:27]3[CH:28]=[N:29][CH:30]=[N:31][CH:32]=3)=[CH:25][C:10]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)=[O:12])=[CH:9][N:8]=2)[CH2:3][CH2:2]1>C(O)(=O)C.O=[Pt]=O>[N:31]1[CH:32]=[C:27]([C:26]2[C:7]([CH:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)=[N:8][CH:9]=[C:10]([CH:25]=2)[C:11]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([O:20][C:21]([F:24])([F:22])[F:23])=[CH:18][CH:19]=2)=[O:12])[CH:28]=[N:29][CH:30]=1

Participants

4

Reactant 1

HCID 72203421HCID 72203421, compound

Product 1

HCID 72203420HCID 72203420, compound

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 176Acetic AcidSolvent

Procedure

A solution of 6-(3,6-dihydro-2h-pyran-4-yl)-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Example 44, 80 mg, 0.180 mmol) in acetic acid (5 mL) was hydrogenated in the presence of PtO2 (16 mg) at RT and atmospheric pressure for 67 h. The RM was filtered through Celite® and the solvent was evaporated off under reduced pressure to give the crude product which was purified by reverse phase chromatography (MPLC, Lichroprep® 15-25 μm column, water+0.1% formic acid/MeCN+0.1% formic acid, gradient 5% to 39% MeCN+0.1% formic acid). Fractions containing the pure product were combined, basified with NaHCO3 and extracted with EtOAc. The combined extracts were dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a residue which was purified by preparative TLC (Silica gel 60 F 254, 0.5 mm, eluent was DCM/MeOH 19:1). The product was dissolved with MeCN, filtered and the filtrate was evaporated off under reduced pressure to afford the title compound as white crystalline solid. HPLC (Condition 3) tR=5.09 min, UPLC-MS (Condition 2) m/z=444.4 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.54-1.65 (m, 2H) 1.85-2.02 (m, 2H) 2.88-3.03 (m, 1H) 3.19-3.28 (m, 2H) 3.80-3.93 (m, 2H) 7.37 (d, J=8.99 Hz, 2H) 7.86 (m, J=9.00 Hz, 2H) 8.23 (d, J=1.96 Hz, 1H) 8.96 (s, 2H) 9.15 (d, J=1.95 Hz, 1H) 9.30 (s, 1H) 10.56 (s, 1H).

Workup

  1. filtrationThe RM was filtered through Celite®
  2. customthe solvent was evaporated off under reduced pressure
  3. customto give the crude product which
  4. customwas purified by reverse phase chromatography (MPLC, Lichroprep® 15-25 μm column, water+0.1% formic acid/MeCN+0.1% formic acid, gradient 5% to 39% MeCN+0.1% formic acid)
  5. additionFractions containing the pure product
  6. extractionextracted with EtOAc
  7. dry with materialThe combined extracts were dried over Na2SO4
  8. customthe solvent was evaporated off under reduced pressure
  9. customto give a residue which
  10. customwas purified by preparative TLC (Silica gel 60 F 254, 0.5 mm, eluent was DCM/MeOH 19:1)
  11. dissolutionThe product was dissolved with MeCN
  12. filtrationfiltered
  13. customthe filtrate was evaporated off under reduced pressure

Sources & evidence

ORD record
ord-1a4282d00fa94163a472db4af625c8b2
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

Loading…