Water → HCID 178433090, compound

HRID 1882487Notes

Reaction equation

HRID 1882487 reaction equation
[C:1]([C:4]1[S:8][C:7]([N:9]2[CH2:13][CH2:12][N:11]([CH2:14][CH:15]3[CH2:17][C:16]3([F:19])[F:18])[C:10]2=[O:20])=[N:6][C:5]=1[CH3:21])(=O)[CH3:2].O.[NH2:23]N.O.C[N:27]([CH3:30])C=O>>[F:18][C:16]1([F:19])[CH2:17][CH:15]1[CH2:14][N:11]1[CH2:12][CH2:13][N:9]([C:7]2[S:8][C:4]([C:1]3[CH:2]=[CH:30][NH:27][N:23]=3)=[C:5]([CH3:21])[N:6]=2)[C:10]1=[O:20]

Participants

5

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 24654Hydrazine hydrate (1:1)HCID 57919889(5-Acetyl-4-methylthiazol-2-yl)-3-((2,2-difluorocyclopropyl)methyl)imidazolidin-2-one

Product 1

HCID 178433090HCID 178433090, compoundYield 90%

Conditions

Temperature
96 °C

Procedure

A mixture of 1-(5-acetyl-4-methylthiazol-2-yl)-3-((2,2-difluorocyclopropyl)-methyl)imidazolidin-2-one (0.32 g, 1.00 mmol) and N,N-dimethylformamidediemthyl acetal (0.24 g, 2.00 mmol) in anhydrous N,N-dimethylformamide (10.0 mL) was heated at 96° C. for 16 h and cooled to ambient temperature, followed by the addition of hydrazine monohydrate (1.0 mL). The mixture was heated at 96° C. for 0.5 h and cooled to ambient temperature, followed by the addition of water (20.0 mL). The pale yellow solid formed was collected by filtration and triturated with ethyl acetate and methanol to afford the title compound as a yellow solid (0.21 g, 90%): mp 227-230° C.; 1H NMR (300 MHz, DMSO-d6) δ 12.89 (s, 1H), 7.76 (s, 1H), 6.41 (s, 1H), 3.97 (t, J=9.0 Hz, 2H), 3.63-3.47 (m, 3H), 3.18-3.10 (m, 1H), 2.37 (s, 3H), 2.03-1.88 (m, 1H), 1.67-1.55 (m, 1H), 1.36-1.25 (m, 1H); 13C NMR (75 MHz, DMSO-d6) δ 155.8, 155.5, 144.0, 142.4, 130.3, 118.7, 114.9 (t), 103.2, 42.5, 42.2, 41.2 (d), 20.4 (t), 15.1 (t); MS (ES+) m/z 340.9 (M+1).

Workup

  1. temperaturecooled to ambient temperature
  2. temperatureThe mixture was heated at 96° C. for 0.5 h
  3. temperaturecooled to ambient temperature
  4. customThe pale yellow solid formed
  5. filtrationwas collected by filtration
  6. customtriturated with ethyl acetate and methanol

Sources & evidence

ORD record
ord-638724e9c48942649a4f5541f1bdcdf7
Source dataset
uspto-grants-2012_11
Patent number
US08318949B2

Reaction notes

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