Dimethylamine → HCID 68776254, compound

HRID 1398989Notes

Reaction equation

HRID 1398989 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:16]4[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][C:17]=4[CH:18]=O)[CH2:12][CH2:13][CH2:14][CH2:15][N:7]3[C:6]=2[C:5]([CH:29]([CH2:32][CH3:33])[CH2:30][CH3:31])=[CH:4][CH:3]=1.[CH3:34][NH:35][CH3:36].[BH4-].[Na+]>O1CCCC1.C(O)C.CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4]>[ClH:1].[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:16]4[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][C:17]=4[CH2:18][N:35]([CH3:36])[CH3:34])[CH2:12][CH2:13][CH2:14][CH2:15][N:7]3[C:6]=2[C:5]([CH:29]([CH2:32][CH3:33])[CH2:30][CH3:31])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 674DimethylamineHCID 4311764Sodium borohydrideHCID 57785978HCID 57785978, compound

Product 1

HCID 68776254HCID 68776254, compound

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-[10-chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazol-1-yl]-5-(trifluoromethoxy)benzaldehyde (48.9 mg, 0.102 mmol) in tetrahydrofuran (0.5 mL) and ethanol (0.2 mL) was added dimethylamine (2.0 M solution in tetrahydrofuran, 250 μL, 0.509 mmol). The reaction mixture was stirred at room temperature for 14 hr. To the mixture were added anhydrous sodium borohydride (46.2 mg, 1.22 mmol) and titanium tetraisopropoxide (60.3 μL, 0.204 mmol). The reaction mixture was stirred at room temperature for 9 hr and warmed to 40° C. and stirred for 14 hr. The reaction mixture was quenched with aqueous ammonia at 0° C. The precipitate was filtered and the filtrate was extracted with ethyl acetate (×3). The combined organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by basic silica gel column chromatography eluting with a 0-15% ethyl acetate/n-hexane gradient mixture. The residue was dissolved into ethyl acetate and to the solution was added 4.0 M hydrochloric acid in ethyl acetate (0.20 mL), and the mixture was stirred for 5 min, and concentrated in vacuo to give the title compounds as a colorless amorphous (38.1 mg, 0.0698 mol, 69%).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 9 hr
  2. temperaturewarmed to 40° C.
  3. stirringstirred for 14 hr
  4. customThe reaction mixture was quenched with aqueous ammonia at 0° C
  5. filtrationThe precipitate was filtered
  6. extractionthe filtrate was extracted with ethyl acetate (×3)
  7. washThe combined organic layer was washed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by basic silica gel column chromatography
  12. washeluting with a 0-15% ethyl acetate/n-hexane gradient mixture
  13. dissolutionThe residue was dissolved into ethyl acetate and to the solution
  14. additionwas added 4.0 M hydrochloric acid in ethyl acetate (0.20 mL)
  15. stirringthe mixture was stirred for 5 min
  16. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a6ead8cb7e154f1b95c84cab5ec72db5
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

Loading…