Dimethylformamide → HCID 66692405, compound

HRID 1048992Notes

Reaction equation

HRID 1048992 reaction equation
[Si]([O:8][CH2:9][CH2:10][NH:11][C:12]1[C:13]([NH2:20])=[CH:14][C:15]([F:19])=[C:16]([F:18])[CH:17]=1)(C(C)(C)C)(C)C.CN(C=O)C.OOS([O-])=O.[K+].[F:32][C:33]1[CH:34]=[N:35][CH:36]=[C:37]([CH:40]=1)[CH:38]=O>O>[F:19][C:15]1[C:16]([F:18])=[CH:17][C:12]2[N:11]([CH2:10][CH2:9][OH:8])[C:38]([C:37]3[CH:36]=[N:35][CH:34]=[C:33]([F:32])[CH:40]=3)=[N:20][C:13]=2[CH:14]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 141411595-Fluoropyridine-3-carbaldehydeHCID 23707502Potassium hydroxy sulfiteHCID 86703088HCID 86703088, compound

Product 1

HCID 66692405HCID 66692405, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred solution of N1-(2-(tert-butyldimethylsilyloxy)ethyl)-4,5-difluorobenzene-1,2-diamine (38; 0.09 g, 0.0003 mol) in the mixture of DMF (3 ml) and water (0.3 ml) was added OXONE® (0.218 g, 0.0004 mol) and followed by 5-fluoronicotinaldehyde (0.041 g, 0.0003 mol) was added portion wise under cooling condition with constant stirring. The reaction mixture was allowed to stir at room temperature for 3 h. The reaction mixture was concentrated and diluted with cold water (10 ml) and extracted with ethyl acetate (3×15 ml). The combined organic layers were washed with brine dried over Na2SO4 and concentrated in vacuo and purified by column chromatography on silica gel to afford the desired product 2-[5,6-difluoro-2-(5-fluoropyridin-3-yl)-1H-benzimidazol-1-yl]ethanol as an off white solid. 1H NMR (400 MHz, DMSO-d6), δ: 8.93 (s, 1H), 8.77 (m, 1H), 8.33 (m, 1H), 7.96 (m, 1H), 7.81 (m, 1H), 5.09-5.11 (t, J=5.2 Hz, 1H), 4.35-4.38 (t, J=5.0 Hz, 2H), 3.75-3.76 (m, 2H). LCMS (ES) m/e MS (M+1=294) Purity 99.33%.

Workup

  1. additionwas added portion wise
  2. temperatureunder cooling condition with constant stirring
  3. concentrationThe reaction mixture was concentrated
  4. additiondiluted with cold water (10 ml)
  5. extractionextracted with ethyl acetate (3×15 ml)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. custompurified by column chromatography on silica gel

Sources & evidence

ORD record
ord-f21a601fbd824515b02a9febc40947e7
Source dataset
uspto-grants-2016_07
Patent number
US09382226B2

Reaction notes

Loading…