Sodium hydride → 2-(4-ethoxy-2-oxo-2,3-dihydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(6-methoxy-pyridin-3-yl)-acetamide

HRID 900128

Reaction equation

HRID 900128 reaction equation
[CH2:1]([O:3][C:4]1[CH2:10][C:9](=[O:11])[NH:8][C:7]2[CH:12]=[CH:13][CH:14]=[CH:15][C:6]=2[N:5]=1)[CH3:2].[H-].[Na+].Br[CH2:19][C:20]([N:22]([CH:31]([CH3:33])[CH3:32])[C:23]1[CH:24]=[N:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=1)=[O:21]>CN(C=O)C.O.[Cl-].[Na+].O.C(Cl)Cl>[CH2:1]([O:3][C:4]1[CH2:10][C:9](=[O:11])[N:8]([CH2:19][C:20]([N:22]([CH:31]([CH3:33])[CH3:32])[C:23]2[CH:24]=[N:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=2)=[O:21])[C:7]2[CH:12]=[CH:13][CH:14]=[CH:15][C:6]=2[N:5]=1)[CH3:2]

Participants

8

Reactant 3

HCID 24758Sodium hydrideHCID 589579112-bromo-N-isopropyl-N-(6-methoxy-pyridin-3-yl)-acetamideHCID 589579152H-1,5-Benzodiazepin-2-one, 4-ethoxy-1,3-dihydro-

Product 1

HCID 589579092-(4-ethoxy-2-oxo-2,3-dihydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(6-methoxy-pyridin-3-yl)-acetamide

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-ethoxy-1,3-dihydro-benzo[b][1,4]diazepin-2-one (Preparation 3(A) (2 g, 9.79 mmol) in DMF (40 mL) at 0° C. was added NaH (60% in oil, 431 mg, 10.8 mmol). The reaction was stirred at 0° C. for 0.5 hour and a solution of 2-bromo-N-isopropyl-N-(6-methoxy-pyridin-3-yl)-acetamide (Preparation 1(B) (2.95 g, 10.28 mmol) in DMF (5 mL) was added. The reaction was stirred at room temperature for 2 hours and was diluted with water, brine, and CH2Cl2. The aqueous solution was washed with CH2Cl2 (3×) and the combined organics were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. Purification by medium pressure chromatography eluting with a solvent gradient (hexanes to 70% EtOAc in hexanes) provided 2.87 g of 2-(4-ethoxy-2-oxo-2,3-dihydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(6-methoxy-pyridin-3-yl)-acetamide. 1H NMR (CDCl3) δ 8.14 (s) and 7.93 (s, total 1H), 7.54 (m, 1H), 7.31 (m, 1H), 7.24-7.08 (m, 3H), 6.80 (m, 1H), 5.05 (m, 1H), 4.29 (m, 2H), 4.09 (m, 1H), 3.95 (m, 3H), 3.67 (d, 1H), 3.31 (d, 1H), 3.08 (d, 1H), 1.32 (m, 3H), 1.09 (m, 6H).

Workup

  1. additionwas added
  2. stirringThe reaction was stirred at room temperature for 2 hours
  3. washThe aqueous solution was washed with CH2Cl2 (3×)
  4. washthe combined organics were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by medium pressure chromatography
  9. washeluting with a solvent gradient (hexanes to 70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-cef898bf3f8340149389efdfb07b21d1
Source dataset
uspto-grants-2008_04
Patent number
US07358242B2

Linked notes

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