Cesium carbonate → 6-((2-(4-chlorophenylamino)pyrimidin-5-yl)methoxy)quinolin-2(1H)-one

HRID 77452Notes

Reaction equation

HRID 77452 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH:6]=[CH:5]2.C([O-])([O-])=O.[Cs+].[Cs+].Cl[CH2:20][C:21]1[CH:22]=[N:23][C:24]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=2)=[N:25][CH:26]=1>CN(C=O)C.O>[Cl:34][C:31]1[CH:30]=[CH:29][C:28]([NH:27][C:24]2[N:23]=[CH:22][C:21]([CH2:20][O:1][C:2]3[CH:3]=[C:4]4[C:9](=[CH:10][CH:11]=3)[NH:8][C:7](=[O:12])[CH:6]=[CH:5]4)=[CH:26][N:25]=2)=[CH:33][CH:32]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 1770652,6-DihydroxyquinolineHCID 866797335-(chloromethyl)-N-(4-chlorophenyl)pyrimidin-2-amine

Product 1

HCID 866797376-((2-(4-chlorophenylamino)pyrimidin-5-yl)methoxy)quinolin-2(1H)-oneYield 29.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 6-hydroxyquinolin-2(1H)-one (0.057 g, 0.354 mmol), Cs2CO3 (0.192 g, 0.590 mmol) and 5-(chloromethyl)-N-(4-chlorophenyl)pyrimidin-2-amine (0.1 g, 0.394 mmol) in DMF (2.5 mL) was stirred at room temperature for 18 h. The reaction was diluted with water and the resulting suspension filtered. The bright yellow filter cake was taken up in methanol and the mixture was stirred for 1 h. The suspension was filtered and the yellow solid was washed with methanol and dried. The solid was further stirred in DCM/MeOH for 2 days. The mixture was filtered, and the filter cake washed with methanol and dried to give 6-((2-(4-chlorophenylamino)pyrimidin-5-yl)methoxy)quinolin-2(1H)-one as a brown solid (0.04 g, 26%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.68 (1H, s), 9.95 (1H, s), 8.64 (2H, s), 7.72-7.92 (3H, m), 7.12-7.47 (5H, m), 6.52 (1H, d, J=9.54 Hz), 5.04 (2H, s). LCMS: R.T.=3.77 min; [M+H]+=378.93.

Workup

  1. filtrationthe resulting suspension filtered
  2. stirringthe mixture was stirred for 1 h
  3. filtrationThe suspension was filtered
  4. washthe yellow solid was washed with methanol
  5. customdried
  6. stirringThe solid was further stirred in DCM/MeOH for 2 days
  7. filtrationThe mixture was filtered
  8. washthe filter cake washed with methanol
  9. customdried

Sources & evidence

ORD record
ord-ec070130bd174e15b0ece54e1cf1b774
Source dataset
uspto-grants-2014_09
Patent number
US08841301B2

Reaction notes

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