Potassium Carbonate → HCID 67492285, compound

HRID 1921466Notes

Reaction equation

HRID 1921466 reaction equation
[Cl:1][CH2:2][C:3]([NH:5][CH2:6][C:7]1[S:8][C:9]([C:12]2[CH:17]=[C:16]([CH2:18][CH3:19])[C:15](=[O:20])[NH:14][C:13]=2[CH3:21])=[CH:10][CH:11]=1)=[O:4].[NH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.Cl.CCOC(C)=O>[ClH:1].[CH2:18]([C:16]1[C:15](=[O:20])[NH:14][C:13]([CH3:21])=[C:12]([C:9]2[S:8][C:7]([CH2:6][NH:5][C:3](=[O:4])[CH2:2][N:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)=[CH:11][CH:10]=2)[CH:17]=1)[CH3:19]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 31268PyrrolidineHCID 67492327HCID 67492327, compound

Product 1

HCID 67492285HCID 67492285, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 21866389Hydrogen chloride-ethyl acetateSolvent

Procedure

To a solution of 5-(5-aminomethylthiophen-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one (0.5 g, 2 mmol) and triethylamine (0.6 mL) in THF (5 mL) and dichloromethane (20 mL) is added chloroacetyl chloride (0.24 mL, 3 mmol) at 0° C. After 2 hr at rt, the mixture is quenched with aqueous NaHCO3 solution, and extracted with EtOAc. The extracts are washed with water and brine, dried over sodium sulfate, filtered and concentrated. The residue is chromatographed on SiO2, eluting with CH2Cl2-5% MeOH to afford 0.3 g of 2-chloro-N-[5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-thiophen-2-ylmethyl]-acetamide. A mixture of so formed 2-chloro-N-[5-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-thiophen-2-ylmethyl]-acetamide (0.15 g, 0.46 mmol), and excess of pyrrolidine and potassium carbonate in acetonitrile (10 mL) is heated for 6 hr at 75° C., and extracted with EtOAc. The extracts are washed with water and brine, dried over sodium sulfate, filtered and concentrated. The residue is chromatographed on SiO2, eluting with CH2Cl2-10% MeOH to afford the free base, which is dissolved in HCl-EtOAc and concentrated. Lyophilization in acetonitrile and water affords 60 mg (33%) of N-[5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophen-2-ylmethyl]-2-(pyrrolidin-1-yl)acetamide hydrochloride as a solid. LC/MS: RT 1.93 min; m/e 360 (M+H); 1H NMR (DMSO-d6, δ, ppm): 10.5 (1H, brs), 9.4 (1H, t), 7.2 (1H, s), 6.98 (1H, d), 6.95 (1H, d), 4.5 (2H, d), 4.1 (2H, d), 3.55 (2H, brs), 3.02 (2H, brs), 2.4 (2H, q), 2.25 (3H, s), 1.8-2.05 (4H, m), 1.22 (3H, t).

Workup

  1. extractionextracted with EtOAc
  2. washThe extracts are washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue is chromatographed on SiO2
  7. washeluting with CH2Cl2-10% MeOH
  8. customto afford the free base, which
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-2586644f9fef4f93a92f21bbed52056e
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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