Potassium Carbonate → N-Benzyl-5-(4-(2-cyclopropylethoxy)-2-oxopyridin-1(2H)-yl)-3-methylthiophene-2-carboxamide

HRID 1887312Notes

Reaction equation

HRID 1887312 reaction equation
[CH2:1]([NH:8][C:9]([C:11]1[S:12][C:13]([N:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][C:18]2=[O:24])=[CH:14][C:15]=1[CH3:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].CC1C=CC(S(O[CH2:42][CH2:43][CH:44]2[CH2:46][CH2:45]2)(=O)=O)=CC=1>CN(C)C=O>[CH2:1]([NH:8][C:9]([C:11]1[S:12][C:13]([N:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:42][CH2:43][CH:44]3[CH2:46][CH2:45]3)=[CH:19][C:18]2=[O:24])=[CH:14][C:15]=1[CH3:16])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 13568392Toluene-4-sulfonic acid 2-cyclopropyl-ethyl esterHCID 54742340N-benzyl-5-(4-hydroxy-2-oxopyridin-1(2H)-yl)-3-methylthiophene-2-carboxamide

Product 1

HCID 24985791N-Benzyl-5-(4-(2-cyclopropylethoxy)-2-oxopyridin-1(2H)-yl)-3-methylthiophene-2-carboxamideYield 58.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of N-benzyl-5-(4-hydroxy-2-oxopyridin-1(2H)-yl)-3-methylthiophene-2-carboxamide (0.20 g, 0.59 mmol) in N,N-dimethylformamide (4 mL) at ambient temperature was added potassium carbonate (0.082 g, 0.59 mmol), followed by the addition of 2-cyclopropylethyl 4-methylbenzenesulfonate (0.13 g, 0.59 mmol). The reaction mixture was stirred at 70° C. for 2 hours, and then allowed to cool to ambient temperature and partitioned between ethyl acetate (50 mL) and water (25 mL). The organic layer was washed with brine (25 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography eluting with 40% ethyl acetate in hexanes to afford the title compound as a colorless solid (0.14 g, 58%): mp 134-136° C.; 1H NMR (300 MHz, CDCl3) δ 7.52 (d, J=7.8 Hz, 1H), 7.36-7.27 (m, 5H), 6.83 (s, 1H), 6.18 (t, J=5.6 Hz, 1H), 6.06 (dd, J=7.8, 2.6 Hz, 1H), 5.95 (d, J=2.7 Hz, 1H), 4.58 (d, J=5.6 Hz, 2H), 4.02 (t, J=6.6 Hz, 2H), 2.53 (s, 3H), 1.72-1.64 (m, 2H), 0.89-0.73 (m, 1H), 0.55-0.45 (m, 2H), 0.15-0.08 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 167.2, 162.9, 162.3, 139.7, 139.6, 138.0, 134.3, 128.7, 127.8, 127.5, 126.9, 121.9, 103.4, 97.4, 68.8, 43.9, 33.6, 15.9, 7.6, 4.2; MS (ES+) m/z 409.3 (M+1).

Workup

  1. temperatureto cool to ambient temperature
  2. custompartitioned between ethyl acetate (50 mL) and water (25 mL)
  3. washThe organic layer was washed with brine (25 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customThe residue was purified by column chromatography
  8. washeluting with 40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-5988f6a8fab349209d40f40a183ef5c7
Source dataset
uspto-grants-2013_08
Patent number
US08501746B2

Reaction notes

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