Phenol → 6-(4-fluoro-phenyl)-2-phenoxymethyl-6H-imidazo[1,2-c]pyrimidin-5-one

HRID 538240Notes

Reaction equation

[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[CH2:9][C:10]1[N:11]=[C:12]2[CH:17]=[CH:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[C:14](=[O:25])[N:13]2[CH:26]=1.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[F:24][C:21]1[CH:22]=[CH:23][C:18]([N:15]2[CH:16]=[CH:17][C:12]3=[N:11][C:10]([CH2:9][O:7][C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)=[CH:26][N:13]3[C:14]2=[O:25])=[CH:19][CH:20]=1

Participants

Conditions

Temperature: 90 °C

Procedure

Phenol (40 mg, 0.24 mmol) was added to a stirred suspension of 2-chloromethyl-6-(4-fluoro-phenyl)-6H-imidazo[1,2-c]pyrimidin-5-one (0.107 g, 0.38 mmol) and K2CO3 (0.160 g, 1.15 mmol) in ACN (3 mL). The mixture was stirred at 90° C. for 16 hours and then the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM with a gradient of 0/100 to 20/80). The desired fractions were collected and the solvents evaporated in vacuo. The product was triturated with diethyl ether to yield 6-(4-fluoro-phenyl)-2-phenoxymethyl-6H-imidazo[1,2-c]pyrimidin-5-one (0.12 g, 90% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 5.20 (s, 2H), 6.70 (d, J=7.8 Hz, 1H), 6.98 (t, J=7.2 Hz, 1H), 7.03 (d, J=8.1 Hz, 2H), 7.12 (d, J=7.8 Hz, 1H), 7.19-7.25 (m, 2H), 7.27-7.34 (m, 2H), 7.38-7.45 (m, 2H), 7.83 (s, 1H).

Workup

customthe solvents were evaporated in vacuo
customThe crude product was purified by flash column chromatography (silica
customThe desired fractions were collected
customthe solvents evaporated in vacuo
customThe product was triturated with diethyl ether

Sources & evidence

ORD record: ord-53e1ed5069ea48c6910ddd83cca88745
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08865725B2

Reaction notes

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