Water → 2-(2,4-dioxo-5-pyrid-2-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamide

HRID 343107Notes

Reaction equation

HRID 343107 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[O:11]=[C:12]1[NH:18][C:17]2[CH:19]=[CH:20][CH:21]=[CH:22][C:16]=2[N:15]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)[C:14](=[O:29])[CH2:13]1.Br[CH2:31][C:32]([N:34]([CH:43]([CH3:45])[CH3:44])[C:35]1[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=1)=[O:33].O>C1COCC1.CN(C=O)C>[O:11]=[C:12]1[N:18]([CH2:31][C:32]([N:34]([CH:43]([CH3:45])[CH3:44])[C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)=[O:33])[C:17]2[CH:19]=[CH:20][CH:21]=[CH:22][C:16]=2[N:15]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)[C:14](=[O:29])[CH2:13]1

Participants

7

Reactant 4

HCID 962WaterHCID 2724254Sodium bis(trimethylsilyl)amideHCID 107795342-Bromo-N-isopropyl-N-(4-methoxyphenyl)acetamideHCID 676968392,4-Dioxo-5-pyrid-2-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepine

Product 1

HCID 676961852-(2,4-dioxo-5-pyrid-2-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamideYield 47.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

1.6 mL (1.6 mmol, 1.0 equiv) of 1M NaN(TMS)2 in THF is added dropwise to a solution of 0.40 g (1.6 mmol, 1.0 equiv) of 2,4-dioxo-5-pyrid-2-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepine in 20 mL of DMF at 0° C. After 15 min, a solution of 0.47 g (1.6 mmol, 1.0 equiv) of 2-bromo-N-isopropyl-N-(4-methoxy-phenyl) acetamide in 3 mL of DMF is added dropwise and the resulting green solution is stirred at 0° C. for 25 min. The reaction mixture is poured into 100 mL of H2O and extracted with EtOAc (×2). The organic extract is washed with H2O and brine, dried over MgSO4 and concentrated to a brown oil. Purification by silica gel flash chromatography using EtOAc as eluent gave 0.35 g of the title compound as a light yellow foam: 1H NMR (CDCl3, 300 MHz) δ8.4-6.8 (m, 12H), 5.04 (m, 1H), 4.44 (d, 1H, J=17), 3.94 (d, 1H, J=17), 3.80 (s, 3H), 3.65 (d, 1H, J=12), 3.49 (d, 1H, J=12), 1.11 (d, 6H, J=7); low resolution MS (FAB) m/e 459 (MH+).

Workup

  1. extractionextracted with EtOAc (×2)
  2. extractionThe organic extract
  3. washis washed with H2O and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated to a brown oil
  6. customPurification by silica gel flash chromatography

Sources & evidence

ORD record
ord-c4b3987c75bc4caf958c4b2a28cc15b0
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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