Potassium Carbonate → HCID 58042800, compound

HRID 564115Notes

Reaction equation

HRID 564115 reaction equation
Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][N:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]3[CH:23]=[CH:22][S:21][CH:20]=3)=[CH:13][C:12]2=[O:24])=[CH:5][CH:4]=1.[NH:25]1[CH2:30][CH2:29][CH:28]([NH:31][C:32](=[O:34])[CH3:33])[CH2:27][CH2:26]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[O:24]=[C:12]1[CH:13]=[C:14]([O:17][CH2:18][C:19]2[CH:23]=[CH:22][S:21][CH:20]=2)[CH:15]=[CH:16][N:11]1[CH2:10][CH2:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:2][N:25]2[CH2:30][CH2:29][CH:28]([NH:31][C:32](=[O:34])[CH3:33])[CH2:27][CH2:26]2)=[CH:4][CH:5]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 14451564-AcetamidopiperidineHCID 67006611HCID 67006611, compound

Product 1

HCID 58042800HCID 58042800, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 30 mg (0.45 mmol) 1-[2-(4-hydroxymethyl-phenyl)-ethyl]-4-(thiophen-3-ylmethoxy)-1H-pyridin-2-one (example 4.1a) in 2.0 mL DCM is added 37 μL triethylamine (0.26 mmol) and subsequently 14 μL (0.18 mmol) methanesulfonyl chloride at RT. The reaction mixture is stirred 1 h at RT and additional 18 μL triethylamine (0.13 mmol) and 7 μL (0.09 mmol) methanesulfonyl chloride is added at RT and the reaction mixture is stirred 1 h at RT. 2.0 mL acetonitrile and 25 mg (0.18 mmol) N-piperidin-4-yl-acetamide are added and the reaction mixture is stirred for 1 h. A precipitate is formed and 1 mL of DMF is added and the reaction mixture is stirred overnight. The sole product formed (HPLC-MS analysis) is 1-[2-(4-chloromethyl-phenyl)-ethyl]-4-(thiophen-3-ylmethoxy)-1H-pyridin-2-one. The reaction mixture is diluted with EtOAc, washed twice with water and is dried over MgSO4. After filtration, the solvent is evaporated and 30 mg (95% yield) of 1-[2-(4-chloromethyl-phenyl)-ethyl]-4-(thiophen-3-ylmethoxy)-1H-pyridin-2-one is isolated. To 30 mg (0.09 mmol) 1-[2-(4-chloromethyl-phenyl)-ethyl]-4-(thiophen-3-ylmethoxy)-1H-pyridin-2-one in 2.0 mL DMF is added 26 mg (0.18 mmol) N-piperidin-4-yl-acetamide and 37 mg (0.27 mmol) potassium carbonate at RT. The reaction mixture is stirred overnight at RT, filtered and is directly transferred to a reverse HPLC for purification (Zorbax stable bond, C18; water (0.15% formic acid)/acetonitrile 95:5 to 10:90).

Workup

  1. filtrationfiltered
  2. customis directly transferred to a reverse HPLC for purification (Zorbax stable bond, C18; water (0.15% formic acid)/acetonitrile 95:5 to 10:90)

Sources & evidence

ORD record
ord-db34c53fc2d0433988d9d6dbcc527a52
Source dataset
uspto-grants-2011_11
Patent number
US08067590B2

Reaction notes

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