Sodium hydride → HCID 178430437, compound

HRID 556692Notes

Reaction equation

HRID 556692 reaction equation
[Cl:1][C:2]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:3]=1[C:4]([NH:6][C:7]1[S:8][C:9]([CH3:12])=[CH:10][N:11]=1)=[O:5].[H-].[Na+].Cl[CH2:21][C:22]1[N:23]=[C:24]([CH3:27])[S:25][CH:26]=1>CN(C)C=O.O1CCCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[Cl:1][C:2]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:3]=1[C:4](/[N:6]=[C:7]1\[S:8][C:9]([CH3:12])=[CH:10][N:11]\1[CH2:21][C:22]1[N:23]=[C:24]([CH3:27])[S:25][CH:26]=1)=[O:5]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 7363414-(Chloromethyl)-2-methyl-1,3-thiazoleHCID 3505448HCID 3505448, compound

Product 1

HCID 178430437HCID 178430437, compound

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 8857Ethyl AcetateSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of Example 20A (0.6 g, 2.1 mmol) in N,N-dimethylformamide/tetrahydrofuran (1:4, 20 mL) were added sodium hydride (60% dispersion in mineral oil, 0.1 g, 2.5 mmol), tetrabutylammonium iodide (0.09, 0.23 mmol) and commercially available 4-(chloromethyl)-2-methylthiazole (Maybridge, 0.37 g, 2.5 mmol). The reaction mixture was stirred at 80° C. for 16 hours, cooled, diluted with ethyl acetate (20 mL) and quenched with saturated aqueous NaHCO3 (20 mL). The aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic layers were washed with water (1×25 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-50% ethyl acetate in hexanes) to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.30 (s, 3H), 2.63 (s, 3H), 5.42 (s, 2H), 7.34-7.39 (m, 2H), 7.51 (s, 1H), 7.52 (s, 1H), 7.88 (t, J=1.5 Hz, 1H); MS (ESI+) m/z 398 (M+H)+; Anal. Calculated for C16H13Cl2N3OS2.0.75H2O: C, 48.24; H, 3.29; N, 10.55. Found: C, 46.35; H, 3.46; N, 9.97.

Workup

  1. temperaturecooled
  2. customquenched with saturated aqueous NaHCO3 (20 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×20 mL)
  4. washThe combined organic layers were washed with water (1×25 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-f396c915db7e4767805880aa5810538d
Source dataset
uspto-grants-2011_11
Patent number
US08058293B2

Reaction notes

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