Hydrazine hydrate (1:1) → 1-(4-methyl-5-(1H-pyrazol-5-yl)thiazol-2-yl)-3-(4-(piperidine-1-carbonyl)benzyl)imidazolidin-2-one

HRID 2067632Notes

Reaction equation

HRID 2067632 reaction equation
[C:1]([C:4]1[S:8][C:7]([N:9]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([C:21]([N:23]4[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]4)=[O:22])=[CH:17][CH:16]=3)[C:10]2=[O:29])=[N:6][C:5]=1[CH3:30])(=O)[CH3:2].COC(OC)[N:34]([CH3:36])C.O.[NH2:40]N>CN(C)C=O.C(OCC)(=O)C>[CH3:30][C:5]1[N:6]=[C:7]([N:9]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:16]=[CH:17][C:18]([C:21]([N:23]4[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]4)=[O:22])=[CH:19][CH:20]=3)[C:10]2=[O:29])[S:8][C:4]=1[C:1]1[NH:40][N:34]=[CH:36][CH:2]=1

Participants

6

Reactant 3

HCID 24654Hydrazine hydrate (1:1)HCID 78373Dimethylformamide dimethyl acetalHCID 580313851-(5-Acetyl-4-methylthiazol-2-yl)-3-(4-(piperidine-1-carbonyl)benzyl)imidazolidin-2-one

Product 1

HCID 666309441-(4-methyl-5-(1H-pyrazol-5-yl)thiazol-2-yl)-3-(4-(piperidine-1-carbonyl)benzyl)imidazolidin-2-oneYield 54%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 1-(5-acetyl-4-methylthiazol-2-yl)-3-(4-(piperidine-1-carbonyl)benzyl)imidazolidin-2-one (0.43 g, 1.00 mmol) in N,N-dimethylformamide (10 mL) was added N,N-dimethylformamide dimethyl acetal (0.20 mL, 1.50 mmol). The reaction mixture was heated for 20 hours at 110° C., and hydrazine monohydrate (0.25 mL, 5.14 mmol) was added. The reaction mixture was heated for another 10 minutes at 110° C., then cooled to ambient temperature, diluted with ethyl acetate and washed with water. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography to afford the title compound as a colorless solid in 54% yield (0.26 g): mp 156-157° C. (ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 7.45-7.22 (m, 4H), 4.50 (s, 2H), 4.15-4.01 (m, 2H), 3.69-3.32 (m, 6H), 2.60 (s, 3H), 2.40 (s, 3H), 1.71-1.20 (m, 6H); MS (ES+) m/z 427.1 (M+1).

Workup

  1. temperatureThe reaction mixture was heated for another 10 minutes at 110° C.
  2. temperaturecooled to ambient temperature
  3. washwashed with water
  4. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-a4be2086601f4a5082fe91793cbcdb66
Source dataset
uspto-grants-2012_10
Patent number
US08293768B2

Reaction notes

Loading…