Potassium bis(trimethylsilyl)amide → HCID 19063679, compound

HRID 482346Notes

Reaction equation

HRID 482346 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH:12]1[C:18](=[O:19])[NH:17][C:16]2[CH:20]=[CH:21][CH:22]=[CH:23][C:15]=2[C:14]([C:24]2[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=2)=[N:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].Br[CH2:41][C:42]([N:44]([CH:53]([CH3:55])[CH3:54])[C:45]1[CH:50]=[CH:49][C:48]([O:51][CH3:52])=[CH:47][CH:46]=1)=[O:43]>CN(C)C=O>[CH2:1]([O:8][C:9]([NH:11][CH:12]1[C:18](=[O:19])[N:17]([CH2:41][C:42]([N:44]([CH:53]([CH3:55])[CH3:54])[C:45]2[CH:50]=[CH:49][C:48]([O:51][CH3:52])=[CH:47][CH:46]=2)=[O:43])[C:16]2[CH:20]=[CH:21][CH:22]=[CH:23][C:15]=2[C:14]([C:24]2[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=2)=[N:13]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 10317977HCID 10317977, compoundHCID 107795342-Bromo-N-isopropyl-N-(4-methoxyphenyl)acetamide

Product 1

HCID 19063679HCID 19063679, compoundYield 84.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 1.000 g of 3-(benzyloxycarbonyl-amino)-5-pyridin-3-yl-1,3-dihydro-benzo[e][1,4]diazepin-2-one (2.591 mmol, Pat. App. WO 93/16999) in 7 mL dimethylformamide at 0° C. under nitrogen was treated with 5.44 mL (2.72 mmol) of potassium bis(trimethylsilyl)amide (0.5M in toluene). After stirring for 10 min., a solution of 0.779 g of 2-bromo-N-isopropyl-N-(4-methoxy-phenyl)-acetamide (2.72 mmol), prepared as in Intermediate 5, in 2 mL of dimethylformamide was added to the mixture. The reaction was stirred to ambient temperature over 2 hrs. and then quenched into a mixture of ethyl acetate, water and saturated aqueous brine. The phases were separated and the aqueous phase was back-extracted with ethyl acetate. The organic layers were combined, washed with saturated aqueous brine, dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to a residue. The residue was purified on flash grade silica gel using 9:1 ethyl acetate/hexane. The appropriate fractions were combined, evaporated in vacuo to a foam and triturated with hexane. After evaporation of the hexane in vacuo, the residual solid was dried under high vacuum to provide 1.295 g of the title compound as a tan solid. 1H NMR (300 MHz, d6-DMSO) -- =8.70 (m, 2H), 8.56 (d, 1H, J=8.6), 7.92 (m, 1H), 7.71 (m, 1H), 7.52 (m, 2H), 7.32 (m, 9H), 7.07 (d, 2H, J=8.8), 5.19 (d, 1H, J=8.8), 5.08 (s, 2H), 4.71 (m, 1H), 4.27 (d, 1H, J=16.5), 4.12 (d, 1H, J=16.5), 3.81 (s, 3H), 0.95 (m, 6H); MS (ESI): [M+H]+ =592.

Workup

  1. stirringThe reaction was stirred to ambient temperature over 2 hrs
  2. customand then quenched into a mixture of ethyl acetate, water and saturated aqueous brine
  3. customThe phases were separated
  4. extractionthe aqueous phase was back-extracted with ethyl acetate
  5. washwashed with saturated aqueous brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo to a residue
  9. customThe residue was purified on flash grade silica gel using 9:1 ethyl acetate/hexane
  10. customevaporated in vacuo to a foam
  11. customtriturated with hexane
  12. customAfter evaporation of the hexane in vacuo
  13. customthe residual solid was dried under high vacuum

Sources & evidence

ORD record
ord-38ada1f4be064fba8c11f50f65038bda
Source dataset
uspto-grants-1998_08
Patent number
US05795887

Reaction notes

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