HCID 68290971, compound → HCID 68290549, compound

HRID 538249Notes

Reaction equation

HRID 538249 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:9]2[CH:14]=[CH:13][C:12]3=[N:15][C:16]([CH2:18][O:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[CH:17][N:11]3[C:10]2=[O:26])=[N:6][C:7]=1[CH3:8].[H][H]>CN(C=O)C.CO.[Ni]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:9]2[CH2:14][CH2:13][C:12]3=[N:15][C:16]([CH2:18][O:19][C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)=[CH:17][N:11]3[C:10]2=[O:26])=[N:6][C:7]=1[CH3:8]

Participants

6

Reactant 2

HCID 68290971HCID 68290971, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 68290549HCID 68290549, compoundYield 41%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 6-(5-fluoro-6-methyl-pyridin-2-yl)-2-phenoxymethyl-6H-imidazo[1,2-c]pyrimidin-5-one (20 mg, 0.057 mmol) in a mixture of DMF (0.6 mL) and MeOH (0.6 mL) was hydrogenated in a H-cube reactor (1 mL/min, 30 mm Raney nickel cartridge, 80° C., full hydrogen mode, 1 cycle). The solvents were evaporated in vacuo and the crude product was purified by RP HPLC (C18 XBridge 19×100 5 um, gradient from 80% of 0.1% solution of ammonium formate/ammonium hydroxide buffer pH 9 solution in water and 20% CH3CN to 0% of 0.1% solution of ammonium formate/ammonium hydroxide buffer pH 9 solution in water and 100% ACN) to yield 6-(5-fluoro-6-methyl-pyridin-2-yl)-2-phenoxymethyl-7,8-dihydro-6H-imidazo[1,2-c]pyrimidin-5-one (8.2 mg, 41% yield). 1H NMR (400 MHz, CDCl3) δ ppm 2.49 (d, J=3.0 Hz, 3H), 3.24 (t, J=6.7 Hz, 2H), 4.35 (t, J=6.7 Hz, 2H), 5.02 (s, 2H), 6.97 (br. t, J=7.4, 7.4 Hz, 1H), 7.00-7.05 (m, 2H), 7.27-7.33 (m, 2H), 7.39 (t, J=8.6 Hz, 1H), 7.59 (s, 1H), 7.65 (dd, J=8.8, 3.2 Hz, 1H).

Workup

  1. customwas hydrogenated in a H-cube reactor
  2. customThe solvents were evaporated in vacuo
  3. customthe crude product was purified by RP HPLC (C18 XBridge 19×100 5 um, gradient from 80% of 0.1% solution of ammonium formate/ammonium hydroxide buffer pH 9 solution in water and 20% CH3CN to 0% of 0.1% solution of ammonium formate/ammonium hydroxide buffer pH 9 solution in water and 100% ACN)

Sources & evidence

ORD record
ord-129504ffb3584d0e86c738a4edf4d7aa
Source dataset
uspto-grants-2014_10
Patent number
US08865725B2

Reaction notes

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