6-(4-fluoro-phenyl)-2-phenoxymethyl-6H-imidazo[1,2-c]pyrimidin-5-one → 6-(4-fluoro-phenyl)-2-phenoxymethyl-7,8-dihydro-6H-imidazo[1,2-c]pyrimidin-5-one

HRID 538245Notes

Reaction equation

HRID 538245 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[CH:12][C:11]3=[N:14][C:15]([CH2:17][O:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:16][N:10]3[C:9]2=[O:25])=[CH:4][CH:3]=1>CO.[OH-].[Pd+2].[OH-]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][C:11]3=[N:14][C:15]([CH2:17][O:18][C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)=[CH:16][N:10]3[C:9]2=[O:25])=[CH:4][CH:3]=1

Participants

4

Reactant 1

HCID 682905726-(4-fluoro-phenyl)-2-phenoxymethyl-6H-imidazo[1,2-c]pyrimidin-5-one

Product 1

HCID 682902896-(4-fluoro-phenyl)-2-phenoxymethyl-7,8-dihydro-6H-imidazo[1,2-c]pyrimidin-5-oneYield 57.2%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalyst2×HCID 887MethanolSolvent

Procedure

10% Palladium hydroxide (10 mg, 0.07 mmol) was added to a stirred solution of 6-(4-fluoro-phenyl)-2-phenoxymethyl-6H-imidazo[1,2-c]pyrimidin-5-one (47 mg, 0.14 mmol) in MeOH (50 mL). The mixture was hydrogenated in a Parr reactor at room temperature under H2 atmosphere for 6 hours. Then the mixture was hydrogenated other 7 cycles in a Parr reactor (50 psi) at 50° C. for 16 hours with addition of 10% palladium hydroxide (10 mg, 0.07 mmol) every cycle. The mixture was filtered through a pad of diatomaceous earth and 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 50/50). The desired fractions were collected and the solvents evaporated in vacuo to yield 6-(4-fluoro-phenyl)-2-phenoxymethyl-7,8-dihydro-6H-imidazo[1,2-c]pyrimidin-5-one (27 mg, 57% yield) as a white solid. 1H NMR (400 MHz, CDCl3) 8 ppm 3.29 (t, J=6.7 Hz, 2H), 4.00 (t, J=6.7 Hz, 2H), 5.02 (d, J=0.7 Hz, 2H), 6.94-6.99 (m, 1H), 6.99-7.05 (m, 2H), 7.10-7.17 (m, 2H), 7.27-7.35 (m, 4H), 7.57 (s, 1H).

Workup

  1. customat 50° C.
  2. customfor 16 hours
  3. filtrationThe mixture was filtered through a pad of diatomaceous earth
  4. customthe solvents were evaporated in vacuo
  5. customThe crude product was purified by flash column chromatography (silica
  6. customThe desired fractions were collected
  7. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-60c97173b86c4b3d82f93b502f343e69
Source dataset
uspto-grants-2014_10
Patent number
US08865725B2

Reaction notes

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