Sodium hydride → HCID 24986110, compound

HRID 1887330Notes

Reaction equation

HRID 1887330 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][N:5]([C:8]2[S:9][C:10]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:11]([CH3:13])[N:12]=2)[C:4](=[O:19])[CH:3]=1.[H-].[Na+].Br[CH2:23][CH:24]1[CH2:26][CH2:25]1>CN(C)C=O>[CH:24]1([CH2:23][O:1][C:2]2[CH:7]=[CH:6][N:5]([C:8]3[S:9][C:10]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:11]([CH3:13])[N:12]=3)[C:4](=[O:19])[CH:3]=2)[CH2:26][CH2:25]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 54742342HCID 54742342, compound

Product 1

HCID 24986110HCID 24986110, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of ethyl 2-(4-hydroxy-2-oxopyridin-1(2H)-yl)-4-methylthiazole-5-carboxylate (1.00 g, 3.56 mmol) in N,N-dimethylformamide (10 mL) at 0° C. was added sodium hydride (0.14 g, 5.70 mmol). The reaction mixture was stirred at 0° C. for 30 minutes, then (bromomethyl)cyclopropane (0.58 g, 4.28 mmol) was added. The reaction mixture was stirred at ambient temperature for 16 hours. The solvent was removed at high vacuum and the residue was diluted with dichloromethane (30 mL), washed with brine (25 mL), dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography eluting with ethyl acetate/hexane (1/1) to afford the title compound as a colorless solid (1.15 g, 97%): mp 180-183° C. (hexane/ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 8.68-8.65 (m, 1H), 6.19-6.16 (m, 1H), 5.93 (d, J=2.6 Hz, 1H), 4.31 (q, J=7.1 Hz, 2H), 3.81 (d, J=7.1 Hz, 2H), 2.68 (s, 3H), 1.35 (t, J=7.1 Hz, 3H), 1.31-1.19 (m, 1H), 0.70-0.64 (m, 2H), 0.38-0.33 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 167.6, 162.9, 162.2, 156.6, 155.6, 131.3, 119.6, 104.5, 96.7, 60.9, 17.3, 14.3, 9.8, 9.5, 3.3; MS (ES+) m/z 335.1 (M+1).

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for 16 hours
  2. customThe solvent was removed at high vacuum
  3. additionthe residue was diluted with dichloromethane (30 mL)
  4. washwashed with brine (25 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customThe residue was purified by column chromatography
  9. washeluting with ethyl acetate/hexane (1/1)

Sources & evidence

ORD record
ord-6963594c04f9400e82c84c0485dbe450
Source dataset
uspto-grants-2013_08
Patent number
US08501746B2

Reaction notes

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