Acetic Acid → HCID 178433999, compound

HRID 1882441Notes

Reaction equation

HRID 1882441 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([N:10]2[CH2:14][CH2:13][N:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)[C:11]2=[O:26])[S:5][C:6]=1[C:7]([NH2:9])=O.CO[C:29](OC)([N:31](C)C)[CH3:30].C(O)(=O)C.O.[NH2:41]N>O1CCOCC1>[CH3:1][C:2]1[N:3]=[C:4]([N:10]2[CH2:14][CH2:13][N:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)[C:11]2=[O:26])[S:5][C:6]=1[C:7]1[NH:31][C:29]([CH3:30])=[N:41][N:9]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 24654Hydrazine hydrate (1:1)HCID 878351,1-Dimethoxyethyl(dimethyl)amineHCID 579198594-Methyl-2-(2-oxo-3-(4-(trifluoromethyl)benzyl)imidazolidin-1-yl)thiazole-5-carboxamide

Product 1

HCID 178433999HCID 178433999, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-methyl-2-(2-oxo-3-(4-(trifluoromethyl)benzyl)imidazolidin-1-yl)thiazole-5-carboxamide (0.19 g, 0.50 mmol) in anhydrous 1,4-dioxane (5.0 mL) was added N,N-dimethylacetamide dimethylacetal (0.50 g, 3.50 mmol). The resulting mixture was refluxed for 16 h and concentrated in vacuo and acetic acid (5.0 mL) and hydrazine monohydrate (0.15 g, 3.00 mmol) was slowly added to the residue. The reaction mixture was stirred at 100° C. for 4 h and concentrated in vacuo. The residue was suspended in saturated aqueous sodium bicarbonate solution (150 mL) and extracted with ethyl acetate (3×80 mL). The organic layer was dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography eluted with 2-10% methanol in dichloromethane to afford the title compound as a colorless solid (0.12 g, 58%): mp 273-274° C. (ethyl acetate); 1H NMR (300 MHz, DMSO-d6) δ 13.64 (s, 1H), 7.74 (d, J=8.2 Hz, 2H), 7.55 (d, J=8.2 Hz, 2H), 4.55 (s, 2H), 4.06-4.00 (m, 2H), 3.52-3.47 (m, 2H), 2.57 (s, 3H), 2.38 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 156.4, 156.3, 155.3, 153.0, 145.0, 141.6 (d, JC-F=1 Hz), 128.4, 128.1 (q, 2JC-F=32 Hz), 125.5 (q, 3JC-F=4 Hz), 124.3 (q, 1JC-F=272 Hz), 115.3, 46.5, 42.0, 41.9, 16.7, 11.5; MS (ES+) m/z 422.9 (M+1).

Workup

  1. temperatureThe resulting mixture was refluxed for 16 h
  2. additionwas slowly added to the residue
  3. concentrationconcentrated in vacuo
  4. extractionextracted with ethyl acetate (3×80 mL)
  5. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by column chromatography
  9. washeluted with 2-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-99220b13514b402885b6ec2d060b5d06
Source dataset
uspto-grants-2012_11
Patent number
US08318949B2

Reaction notes

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