Potassium Carbonate → HCID 86696740, compound

HRID 2365885Notes

Reaction equation

HRID 2365885 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]2[N:13]=[C:12]([C:14]3[CH:19]=[CH:18][NH:17][C:16](=[O:20])[CH:15]=3)[CH:11]=[CH:10][N:9]=2)[CH2:3][CH2:2]1.[C:21]([O-])([O-])=O.[K+].[K+].C([Si]([O:34][C:35]1([C:38]2[CH:43]=[CH:42][C:41]([Cl:44])=[C:40]([F:45])[CH:39]=2)[CH2:37][O:36]1)(C)C)(C)(C)C>CN(C=O)C.O>[Cl:44][C:41]1[CH:42]=[CH:43][C:38]([C:35]([OH:34])([CH2:37][OH:36])[CH2:21][N:17]2[CH:18]=[CH:19][C:14]([C:12]3[CH:11]=[CH:10][N:9]=[C:8]([NH:7][CH:4]4[CH2:5][CH2:6][O:1][CH2:2][CH2:3]4)[N:13]=3)=[CH:15][C:16]2=[O:20])=[CH:39][C:40]=1[F:45]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 86696649HCID 86696649, compoundHCID 86696741HCID 86696741, compound

Product 1

HCID 86696740HCID 86696740, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

4-(2-(Tetrahydro-2H-pyran-4-ylamino)pyrimidin-4-yl)pyridin-2(1H)-one (136 mg, 0.500 mmol) and K2CO3 (248 mg, 1.80 mmol) were added to a solution of tert-butyl (2-(4-chloro-3-fluorophenyl)oxiran-2-yloxy)dimethylsilane (200 mg, 0.600 mmol) in DMF (5.0 mL). After being heated at 80° C. overnight, the mixture was diluted with H2O (50 mL) and extracted with EtOAc (3×100 mL). The organic phases were washed with brine (3×30 mL), dried, and concentrated. The residue was dissolved in CH2Cl2, followed by addition of TFA (5.0 mL). The mixture was stirred at room temperature overnight. The solvent was removed under vacuum, and the residue was purified by prep-HPLC to give 1-(2-(4-chloro-3-fluorophenyl)-2,3-dihydroxypropyl)-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridine-2(1H)-one (70 mg, 30% yield). 1H NMR (500 MHz, CD3OD) δ 8.39 (m, 1H), 7.67-7.66 (m, 1H), 7.51-7.49 (m, 1H), 7.45-7.38 (m, 1H), 7.22 (s, 2H), 7.08-7.07 (m, 1H), 6.97-6.95 (m, 1H), 4.69-4.66 (m, 1H), 4.31-4.28 (m, 1H), 4.10 (s, 1H), 4.01-3.99 (m, 2H), 3.72-3.66 (m, 2H), 3.60-3.56 (m, 2H), 2.03-2.00 (m, 2H), 1.67-1.59 (m, 2H); LCMS (ESI) m/z: 475.1 [M+H]+.

Workup

  1. extractionextracted with EtOAc (3×100 mL)
  2. washThe organic phases were washed with brine (3×30 mL)
  3. customdried
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in CH2Cl2
  6. additionfollowed by addition of TFA (5.0 mL)
  7. customThe solvent was removed under vacuum
  8. customthe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-fab9b64310474eeeb82cbf446314687d
Source dataset
uspto-grants-2014_04
Patent number
US08697715B2

Reaction notes

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