Dimethylamine → HCID 68773078, compound

HRID 1398987Notes

Reaction equation

HRID 1398987 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]([CH3:24])=[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:25]([CH2:28][CH3:29])[CH2:26][CH3:27])=[CH:4][CH:3]=1.[CH3:30][NH:31][CH3:32].[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]([CH3:24])=[CH:20][C:17]=4[CH2:18][N:31]([CH3:32])[CH3:30])[CH2:12][CH2:13][CH2:14][CH2:15][N:7]3[C:6]=2[C:5]([CH:25]([CH2:28][CH3:29])[CH2:26][CH3:27])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 674DimethylamineHCID 4311764Sodium borohydrideHCID 57786113HCID 57786113, compound

Product 1

HCID 68773078HCID 68773078, 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-methylbenzaldehyde (50.0 mg, 0.122 mmol) in tetrahydrofuran (0.5 mL) and ethanol (0.5 mL) was added dimethylamine (2.0 M solution in tetrahydrofuran, 305 μL, 0.610 mmol). The reaction mixture was stirred at room temperature for 12 hr. To the mixture were added sodium borohydride (9.23 mg, 0.244 mmol) and titanium tetraisopropoxide (72.0 μL, 0.244 mmol). The reaction mixture was stirred at room temperature for 9 hr. The reaction mixture was quenched with aqueous ammonia at 0° C. and extracted with ethyl acetate (×3). The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by basic silica gel column chromatography eluting with a 0-20% ethyl acetate/n-hexane gradient mixture. The residue was dissolved into ethyl acetate and 4.0 M hydrochloric acid in ethyl acetate was added (0.20 mL) to the solution. The mixture was stirred for 5 min, and concentrated in vacuo to give the title compounds as an amorphous (30.0 mg, 0.0631 mmol, 52%).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 9 hr
  2. customThe reaction mixture was quenched with aqueous ammonia at 0° C.
  3. extractionextracted with ethyl acetate (×3)
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by basic silica gel column chromatography
  9. washeluting with a 0-20% ethyl acetate/n-hexane gradient mixture
  10. dissolutionThe residue was dissolved into ethyl acetate and 4.0 M hydrochloric acid in ethyl acetate
  11. additionwas added (0.20 mL) to the solution
  12. stirringThe mixture was stirred for 5 min
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bdc305b655244beba621fa0e0ba5d400
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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