Chlorodifluoromethane → HCID 57531293, compound

HRID 1455136Notes

Reaction equation

HRID 1455136 reaction equation
[NH2:1][C:2]1[NH:6][C:5](=[O:7])[C:4]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[C:21]([C:26]3[CH:27]=[N:28][CH:29]=[N:30][CH:31]=3)[CH:20]=2)([C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=2)[N:3]=1.[OH-].[K+].Cl[CH:35]([F:37])[F:36]>CN(C)C=O>[NH2:1][C:2]1[N:6]([CH:35]([F:37])[F:36])[C:5](=[O:7])[C:4]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[C:21]([C:26]3[CH:31]=[N:30][CH:29]=[N:28][CH:27]=3)[CH:20]=2)([C:8]2[CH:9]=[CH:10][C:11]([O:14][C:15]([F:17])([F:16])[F:18])=[CH:12][CH:13]=2)[N:3]=1

Participants

5

Reactant 3

HCID 6372ChlorodifluoromethaneHCID 14797Potassium HydroxideHCID 57531329HCID 57531329, compound

Product 1

HCID 57531293HCID 57531293, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-45 °C

Procedure

A solution of 2-amino-5-[4-fluoro-3-(pyrimidin-5-yl)phenyl]-5-[4-(trifluoromethoxy)phenyl]-3,5-dihydro-4H-imidazol-4-one (0.398 g, 0.92 mmol) in dimethylformamide is treated with KOH (0.057 g, 1.01 mmol), cooled to −45° C., and bubbled with chlorodifluoromethane (1.40 g, 17.6 mmol). The reaction vessel is sealed and heated at 70° C. for 18 h. The reaction is cooled to room temperature, quenched by careful addition to water, extracted with ethyl acetate, diluted with brine and extracted again with ethyl acetate. The combined extracts are washed with brine, dried over sodium sulfate and concentrated. The resultant residue is purified twice by flash chromatography (silica, 95:5:0.5 to 90:10:0.5 methylene chloride/methanol/concentrated ammonium hydroxide and 100:0 to 98:2 methylene chloride/methanol as eluents) to afford the title compound as a white solid, 0.064 g (14% yield), mp 82-94° C., identified by HNMR, infrared and mass spectral analyses. 1H NMR (500 MHz, CDCl3) δ 9.21 (s, 1H), 8.89 (s, 2H), 7.64-7.60 (m, 2H), 7.54 (d, J=8.8 Hz, 2H), 7.23-7.18 (m, 3H), 6.95 (t, J=58 Hz, 1H), 4.92 (br s, 2H); IR (ATR) 3497, 3309, 3149, 1761, 1678, 1497, 1449, 1416, 1252, 1212, 1162 cm−1; ESI MS m/z 482 [C21H13F6N5O2+H]+;

Workup

  1. customThe reaction vessel is sealed
  2. temperatureheated at 70° C. for 18 h
  3. temperatureThe reaction is cooled to room temperature
  4. customquenched by careful addition to water
  5. extractionextracted with ethyl acetate
  6. additiondiluted with brine
  7. extractionextracted again with ethyl acetate
  8. washThe combined extracts are washed with brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated
  11. customThe resultant residue is purified twice by flash chromatography (silica, 95:5:0.5 to 90:10:0.5 methylene chloride/methanol/concentrated ammonium hydroxide and 100:0 to 98:2 methylene chloride/methanol as eluents)

Sources & evidence

ORD record
ord-66685b3b7d0345daaf04178ce1a8df35
Source dataset
uspto-grants-2009_01
Patent number
US07482349B2

Reaction notes

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