Sodium hydride → 2-(1-cyclohexyl-5-oxo-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-N-isopropyl-N-(6-methoxy-pyridin-3-yl)-acetamide

HRID 900132Notes

Reaction equation

HRID 900132 reaction equation
[CH:1]1([C:7]2[N:16]3[C:10]([CH2:11][C:12](=[O:21])[NH:13][C:14]4[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=43)=[N:9][N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Br[CH2:25][C:26]([N:28]([CH:37]([CH3:39])[CH3:38])[C:29]1[CH:30]=[N:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=1)=[O:27]>CN(C=O)C.O>[CH:1]1([C:7]2[N:16]3[C:10]([CH2:11][C:12](=[O:21])[N:13]([CH2:25][C:26]([N:28]([CH:37]([CH3:39])[CH3:38])[C:29]4[CH:30]=[N:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=4)=[O:27])[C:14]4[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=43)=[N:9][N:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 589579112-bromo-N-isopropyl-N-(6-methoxy-pyridin-3-yl)-acetamideHCID 589579321-cyclohexyl-4H,6H-2,3,6,10b-tetraaza-benzo[e]azulen-5-one

Product 1

HCID 589579462-(1-cyclohexyl-5-oxo-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-N-isopropyl-N-(6-methoxy-pyridin-3-yl)-acetamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 1-cyclohexyl-4H,6H-2,3,6,10b-tetraaza-benzo[e]azulen-5-one (Preparation 4(B) (100 mg, 0.354 mmol) in DMF (10 mL) at 0° C. was added NaH (60% in oil, 15 mg, 0.372 mmol). The reaction was stirred at 0° C. for 30 minutes, was cooled to −10° C. and 2-bromo-N-isopropyl-N-(6-methoxy-pyridin-3-yl)-acetamide (Preparation 1(B) (107 mg, 0.372 mmol) in DMF (1 mL) was added. The reaction was stirred at room temperature for 24 h and was diluted with water. The aqueous solution was washed with EtOAc (3×). The combined organic solutions were dried (MgSO4), filtered and concentrated. The residue was purified by medium pressure chromatography eluting with a solvent gradient (1% EtOAc in hexanes to 100% EtOAc) to provide 861.8 mg of 2-(1-cyclohexyl-5-oxo-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-N-isopropyl-N-(6-methoxy-pyridin-3-yl)-acetamide. 1H NMR (CDCl3) δ 8.11-7.48 (m, total 3H), 7.36 (m, 3H), 6.79 (dd, 1H), 4.99 (m, 1H), 4.12 (m, 2H), 3.92 (d, 3H), 3.65 (d) and 3.82 (d, total 1H), 3.46 (dd, 1H), 2.83 (m, 1H), 2.20 (d, 1H), 2.03-1.86 (m, 3H), 1.68 (m, 2H), 1.54 (m, 2H) 1.31-1.41 (m, 2H), 1.07 (m, 6H); MS 489.4 (M+1), 487.4 (M−1).

Workup

  1. temperaturewas cooled to −10° C.
  2. additionwas added
  3. stirringThe reaction was stirred at room temperature for 24 h
  4. washThe aqueous solution was washed with EtOAc (3×)
  5. dry with materialThe combined organic solutions were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by medium pressure chromatography
  9. washeluting with a solvent gradient (1% EtOAc in hexanes to 100% EtOAc)

Sources & evidence

ORD record
ord-cbf0baff6e684b1495246b5a3f469d77
Source dataset
uspto-grants-2008_04
Patent number
US07358242B2

Reaction notes

Loading…