Potassium Carbonate → HCID 89907791, compound

HRID 629092Notes

Reaction equation

HRID 629092 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([OH:7])[CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].[Br:14][C:15]1[C:16](Cl)=[N:17][CH:18]=[C:19]([CH:34]=1)[C:20]([NH:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[CH:25][CH:24]=1)=[O:21]>CN(C=O)C>[Br:14][C:15]1[C:16]([O:7][CH:4]2[CH2:5][CH2:6][O:1][CH2:2][CH2:3]2)=[N:17][CH:18]=[C:19]([CH:34]=1)[C:20]([NH:22][C:23]1[CH:24]=[CH:25][C:26]([O:29][C:30]([F:32])([F:31])[F:33])=[CH:27][CH:28]=1)=[O:21]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 74956Tetrahydro-4H-pyran-4-olHCID 867025955-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 89907791HCID 89907791, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

Tetrahydro-2h-pyran-4-ol (0.361 mL, 3.79 mmol) and K2CO3 (314 mg, 2.275 mmol) were added to a suspension of 5-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 44.2, 300 mg, 0.758 mmol) in DMF (2 mL) and the RM was stirred at 120° C. for 3.5 h. The solvent was evaporated off under reduced pressure. The residue was purified by flash chromatography (RediSep® Silica gel column, 40 g, EtOAc/n-hexane, isocratic 2:8) to afford 5-bromo-6-(tetrahydro-2h-pyran-4-yloxy)-N-(4-(trifluoromethoxy)phenyl)nicotinamide, of which (25 mg, 0.054 mmol) together with pyrimidin-5-ylboronic acid (30 mg, 0.160 mmol), Pd(Ph3P)4 (10 mg, 8.13 μmol) K3PO4 (35 mg, 0.163 mmol) and toluene (0.4 mL) was stirred at 110° C. for 10 h under an argon atmosphere. The cooled RM was diluted with MeOH, filtered through a cartridge of PL-Thiol MP-Resin, and the filtrate was evaporated to dryness under reduced pressure. The residue was purified by preparative SFC (Column 4-EP; gradient 7% to 12% in 6 min.) and lyophilized to afford an off-white powder. UPLC-MS (Condition 2) tR=1.06 min, m/z=461.1 [M+H]+; 1H-NMR (600 MHz, DMSO-d6) δ ppm 1.61-1.75 (m, 2H) 2.04 (m, J=10.00 Hz, 2H) 3.54 (m, J=8.80, 8.80 Hz, 2H) 3.70-3.80 (m, 2H) 5.37-5.47 (m, 1H) 7.39 (d, J=8.47 Hz, 2H) 7.87 (d, J=9.03 Hz, 2H) 8.50 (s, 1H) 8.82 (s, 1H) 9.15 (s, 2H) 9.22 (s, 1H) 10.45 (s, 1H).

Workup

  1. customThe solvent was evaporated off under reduced pressure
  2. customThe residue was purified by flash chromatography (RediSep® Silica gel column, 40 g, EtOAc/n-hexane, isocratic 2:8)

Sources & evidence

ORD record
ord-b8ef82c054f84fe983e65782075ef2d9
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

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