Potassium Carbonate → 4-(4-chlorobenzyloxy)-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-2(1H)-one

HRID 2059845Notes

Reaction equation

[OH:1][C:2]([CH3:23])([CH3:22])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH:16]=[CH:15][C:14](SC)=[N:13][C:12]2=[O:19])=[CH:7][C:6]=1[O:20][CH3:21].[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31][OH:32])=[CH:27][CH:26]=1.C([O-])([O-])=O.[K+].[K+]>CN1C(=O)CCC1.C(Cl)Cl>[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31][O:32][C:14]2[CH:15]=[CH:16][N:11]([C:8]3[CH:9]=[CH:10][C:5]([O:4][CH2:3][C:2]([OH:1])([CH3:23])[CH3:22])=[C:6]([O:20][CH3:21])[CH:7]=3)[C:12](=[O:19])[N:13]=2)=[CH:27][CH:26]=1

Participants

Conditions

Temperature: 145 °C

Procedure

A stirred mixture of 1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-4-(methylthio)pyrimidin-2(1H)-one Part C of Procedure 1 (10 mg, 0.03 mmol), (4-chlorophenyl)methanol (85 mg, 0.6 mmol) and K2CO3 (12 mg, 0.09 mmol) in NMP (0.1 mL) was heated at 145° C. for 60 min, diluted with CH2Cl2, washed with water, dried (MgSO4), and concentrated. The residue was purified by flash chromatography (silica gel/hexane-EtOAc 100:0:0 to 0:100 gradient) to afford the title compound 4-(4-chlorobenzyloxy)-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-2(1H)-one A-8 (5 mg, 36% yield) as a white solid. LC/MS 431 (M+H)+, tR 0.9 min (method 5); 1H NMR (400 MHz, chloroform-D) δ 7.53 (1H, d, J=7.03 Hz), 7.40 (2H, d, J=8.53 Hz), 7.37 (2H, d, J=8.78 Hz), 6.96 (1H, d, J=8.53 Hz), 6.91 (1H, d, J=2.26 Hz), 6.85 (1H, dd, J=8.53, 2.51 Hz), 6.00 (1H, d, J=7.03 Hz), 5.45 (2H, s), 3.86 (3H, s), 3.85 (2H, s), 1.35 (6H, s).

Workup

washwashed with water
dry with materialdried (MgSO4)
concentrationconcentrated
customThe residue was purified by flash chromatography (silica gel/hexane-EtOAc 100:0:0 to 0:100 gradient)

Sources & evidence

ORD record: ord-397c065478c645f1a66a3ea0dd339b9b
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278316B2

Reaction notes

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