Triethylamine → HCID 178480823, compound

HRID 1468789Notes

Reaction equation

HRID 1468789 reaction equation
O[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[CH2:14][CH2:13][C@H:12]([O:15][C:16]3[N:17]([CH3:29])[C:18](=[O:28])[CH:19]=[C:20]([C:22]4[CH:27]=[CH:26][N:25]=[CH:24][N:23]=4)[N:21]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[CH3:42][N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1.C(=O)([O-])[O-].[K+].[K+]>ClCCl.O>[CH3:29][N:17]1[C:18](=[O:28])[CH:19]=[C:20]([C:22]2[CH:27]=[CH:26][N:25]=[CH:24][N:23]=2)[N:21]=[C:16]1[O:15][C@H:12]1[CH2:13][CH2:14][C@H:9]([C:6]2[CH:7]=[CH:8][C:3]([CH2:2][N:46]3[CH2:47][CH2:48][N:43]([CH3:42])[CH2:44][CH2:45]3)=[CH:4][CH:5]=2)[CH2:10][CH2:11]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 531671-MethylpiperazineHCID 178481544HCID 178481544, compound

Product 1

HCID 178480823HCID 178480823, compoundYield 42.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 2-[trans-4-(4-hydroxymethyl-phenyl)cyclohexyloxy]-1-methyl-1H-[4,4′]bipyrimidinyl-6-one (100 mg, 0.255 mmol) and triethylamine (51.6 mg, 0.510 mmol) in dichloromethane (1.3 ml) was added methanesulfonyl chloride (32.1 mg, 0.28 mmol) at 0° C. The mixture was warmed to room temperature and stirred overnight. The mixture was partitioned between water and dichloromethane. The organic layer was washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was dissolved into tetrahydrofuran (1.3 ml) and N,N-dimethylformamide (0.3 ml). 1-Methylpiperazine (30.6 mg, 0.306 mmol) and potassium carbonate (52.8 mg, 0.382 mmol) was added to the solution. The mixture was stirred at 60° C. for 3 hours. The mixture was poured into water, and extracted with chloroform. The organic layer was washed with water (three times), dried over sodium sulfate, and concentrated in vacuo. The residue was purified by NH-silica gel column chromatography (eluent; ethyl acetate) to afford 1-methyl-2-{trans-4-[4-(4-methyl-piperazin-1-ylmethyl)phenyl]cyclohexyloxy}-1H-[4,4′]bipyrimidinyl-6-one as a colorless solid (51.1 mg, 0.108 mmol, 42%).

Workup

  1. customThe mixture was partitioned between water and dichloromethane
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved into tetrahydrofuran (1.3 ml) and N,N-dimethylformamide (0.3 ml)
  6. stirringThe mixture was stirred at 60° C. for 3 hours
  7. extractionextracted with chloroform
  8. washThe organic layer was washed with water (three times)
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by NH-silica gel column chromatography (eluent; ethyl acetate)

Sources & evidence

ORD record
ord-d6344fd8c725438a84600f421457f176
Source dataset
uspto-grants-2015_04
Patent number
US09006232B2

Reaction notes

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