Hydrochloric Acid → HCID 68290315, compound

HRID 538247Notes

Reaction equation

HRID 538247 reaction equation
Cl.[CH3:2][C:3]1[CH:4]=[CH:5][C:6]([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:7][CH:8]=1.[H][H]>CO.[Ni]>[CH3:2][C:3]1[CH:4]=[CH:5][C:6]([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:7][CH:8]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 66551180HCID 66551180, compoundHCID 178418361HCID 178418361, compound2×

Product 1

HCID 68290315HCID 68290315, compoundYield 5%

Reagents, catalysts & solvents 2

HCID 935NickelCatalyst2×HCID 887MethanolSolvent2×

Procedure

A 1.25 M solution of HCl in MeOH (3 mL) was added to a stirred solution of 6-(5-methyl-pyridin-2-yl)-2-phenoxymethyl-6H-imidazo[1,2-c]pyrimidin-5-one (0.1 g, 0.3 mmol) in MeOH (10 mL) was hydrogenated in a H-cube reactor (1 mL/min, 30 mm Raney nickel cartridge, 30° C., full hydrogen mode, 4 cycles) and then (1 mL/min, 30 mm Raney nickel cartridge, RT, full hydrogen mode, 1 cycle). The solvents were evaporated in vacuo and the crude product was purified by flash column chromatography (silica; AcOEt in DCM with a gradient of 0/100 to 100/0 and then 7 M solution of ammonia in MeOH in DCM with a gradient of 0/100 to 2/98). The desired fractions were collected and the solvents evaporated in vacuo. The product was repurified 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-methyl-pyridin-2-yl)-2-phenoxymethyl-7,8-dihydro-6H-imidazo[1,2-c]pyrimidin-5-one (5 mg, 5% yield). 1H NMR (500 MHz, CDCl3) δ ppm 2.35 (s, 3H), 3.24 (t, J=6.6 Hz, 2H), 4.35 (t, J=6.6 Hz, 2H), 5.03 (s, 2H), 6.97 (br. t, J=7.4, 7.4 Hz, 1H), 6.99-7.05 (m, 2H), 7.27-7.33 (m, 2H), 7.57 (dd, J=8.5, 2.2 Hz, 1H), 7.59 (s, 1H), 7.71 (d, J=8.4 Hz, 1H), 8.25 (dd, J=1.6, 0.7 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 flash column chromatography (silica
  4. customThe desired fractions were collected
  5. customthe solvents evaporated in vacuo
  6. customThe product was repurified 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-8da9c7089b1c45a7a522442e90b7595d
Source dataset
uspto-grants-2014_10
Patent number
US08865725B2

Reaction notes

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