HCID 66550974, compound → HCID 66550972, compound

HRID 538246Notes

Reaction equation

HRID 538246 reaction equation
[F:1][C:2]1[CH:26]=[CH:25][C:5]([O:6][CH2:7][C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][N:13]([C:16]4[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=4)[C:12](=[O:23])[N:11]3[CH:24]=2)=[CH:4][CH:3]=1.[H][H]>CCO.[Ni]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][C:8]2[N:9]=[C:10]3[CH2:15][CH2:14][N:13]([C:16]4[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=4)[C:12](=[O:23])[N:11]3[CH:24]=2)=[CH:25][CH:26]=1

Participants

5

Reactant 2

HCID 66550974HCID 66550974, compoundHCID 178418361HCID 178418361, compound2×

Product 1

HCID 66550972HCID 66550972, compoundYield 45.2%

Reagents, catalysts & solvents 2

HCID 935NickelCatalyst2×HCID 702EthanolSolvent

Procedure

A solution of 2-(4-fluoro-phenoxymethyl)-6-(4-fluoro-phenyl)-6H-imidazo[1,2-c]pyrimidin-5-one (0.1 g, 0.28 mmol) in EtOH (25 mL) was hydrogenated in a H-cube reactor (1 mL/min, 30 mm Raney nickel cartridge, 35° C., full hydrogen mode, 3 cycles) and then (1 mL/min, 30 mm Raney nickel cartridge, 40° C., full hydrogen mode, 3 cycles). The solvent was evaporated in vacuo and the crude product was purified by flash column chromatography (silica; AcOEt in DCM with a gradient of 50/50 to 75/25). The desired fractions were collected and the solvents evaporated in vacuo to yield 2-(4-fluoro-phenoxymethyl)-6-(4-fluoro-phenyl)-7,8-dihydro-6H-imidazo[1,2-c]pyrimidin-5-one (45 mg, 45% yield). 1H NMR (500 MHz, CDCl3) δ ppm 3.29 (t, J=6.6 Hz, 2H), 4.00 (t, J=6.6 Hz, 2H), 4.98 (s, 2H), 6.92-7.01 (m, 4H), 7.10-7.18 (m, 2H), 7.29-7.36 (m, 2H), 7.56 (s, 1H).

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe crude product was purified by flash column chromatography (silica
  3. customThe desired fractions were collected
  4. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-d65fb4ceb0224dac9b31ed2ffce6c702
Source dataset
uspto-grants-2014_10
Patent number
US08865725B2

Reaction notes

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