Dimethylformamide → HCID 136146820, compound

HRID 1674411Notes

Reaction equation

HRID 1674411 reaction equation
[F:1][C:2]([F:6])([F:5])[CH2:3]I.[C:7](=[O:10])([O-])[O-:8].[Cs+].[Cs+].[OH:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:25](=[O:26])[N:24]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([C:34]4[C:35]([C:40]#[N:41])=[CH:36][CH:37]=[CH:38][CH:39]=4)=[CH:30][CH:29]=3)[C:23]([CH2:42][CH2:43][CH3:44])=[N:22][C:21]=2[CH3:45])=[CH:16][CH:15]=1.C[N:47](C)C=O>C(OCC)(=O)C>[CH3:45][C:21]1[N:22]=[C:23]([CH2:42][CH2:43][CH3:44])[N:24]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[C:40]3[NH:47][C:7](=[O:10])[O:8][N:41]=3)=[CH:30][CH:29]=2)[C:25](=[O:26])[C:20]=1[C:17]1[CH:16]=[CH:15][C:14]([O:13][CH2:3][C:2]([F:6])([F:5])[F:1])=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 677091,1,1-Trifluoro-2-iodoethaneHCID 67201771HCID 67201771, compound

Product 1

HCID 136146820HCID 136146820, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1,1,1-trifluoro-2-iodoethane (0.91 mL), cesium carbonate (1.5 g) and 4′-{[5-(4-hydroxyphenyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl]methyl}biphenyl-2-carbonitrile (1 g) in N,N-dimethylformamide (10 mL) was stirred overnight at 100° C. The reaction mixture was diluted with ethyl acetate, washed with water, dried over sodium sulfate and concentrated. The residue was dissolved in dimethyl sulfoxide (6 mL), and hydroxylamine hydrochloride (0.79 g) and sodium hydrogen carbonate (1.2 g) were added. The mixture was stirred overnight at 90° C. After cooling, the reaction mixture was diluted with ethyl acetate, washed with water, dried over sodium sulfate and concentrated. The residue was dissolved in tetrahydrofuran (5 mL), and N,N′-carbonyldiimidazole (0.28 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.26 mL) were added. After stirring for 30 min, the reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid, dried over sodium sulfate and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale yellow solid (0.41 g, 62%).

Workup

  1. washwashed with water
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in dimethyl sulfoxide (6 mL)
  5. additionhydroxylamine hydrochloride (0.79 g) and sodium hydrogen carbonate (1.2 g) were added
  6. stirringThe mixture was stirred overnight at 90° C
  7. temperatureAfter cooling
  8. additionthe reaction mixture was diluted with ethyl acetate
  9. washwashed with water
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated
  12. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
  13. additionN,N′-carbonyldiimidazole (0.28 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.26 mL) were added
  14. stirringAfter stirring for 30 min
  15. additionthe reaction mixture was diluted with ethyl acetate
  16. washwashed with 1 M hydrochloric acid
  17. dry with materialdried over sodium sulfate
  18. concentrationconcentrated
  19. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-ec68fa63ee38430d8fdf13a12bbbb8e5
Source dataset
uspto-grants-2011_08
Patent number
US07998968B2

Reaction notes

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