Sodium hydride → HCID 11740397, compound

HRID 222740Notes

Reaction equation

HRID 222740 reaction equation
[CH:1]1([N:5]2[CH2:11][CH2:10][C:9]3[CH:12]=[C:13]([OH:16])[CH:14]=[CH:15][C:8]=3[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Cl[C:20]1[C:21]([N:26]2[CH2:30][CH2:29][CH2:28][C:27]2=[O:31])=[N:22][CH:23]=[CH:24][N:25]=1>CN(C)C=O>[CH:1]1([N:5]2[CH2:6][CH2:7][C:8]3[CH:15]=[CH:14][C:13]([O:16][C:20]4[C:21]([N:26]5[CH2:30][CH2:29][CH2:28][C:27]5=[O:31])=[N:22][CH:23]=[CH:24][N:25]=4)=[CH:12][C:9]=3[CH2:10][CH2:11]2)[CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 100820813-Cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[D]azepin-7-OLHCID 532497151-(3-Chloropyrazin-2-yl)pyrrolidin-2-one

Product 1

HCID 11740397HCID 11740397, compoundYield 48.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

3-Cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ol (E3) (103 mg, 0.47 mmol) was dissolved in dry dimethylformamide (3 ml), cooled to 0° C. and treated with sodium hydride (60% in mineral oil, 20 mg, 0.49 mmol). The mixture was allowed to warm to room temperature over 40 minutes. A solution of 1-(3-chloro-2-pyrazinyl)-2-pyrrolidinone (D46) (103 mg, 0.52 mmol) in dry dimethylformamide (1 ml) was added and the mixture stirred at room temperature for 2 hours and heated at 80° C. for 2.5 hours. The mixture was allowed to cool to room temperature and applied to a SCX column and washed with methanol then a mixture of 0.880 ammonia/methanol (1:9). The basic fractions were combined and concentrated in vacuo and resulting residue was purified by column chromatography eluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.2:1.8:98) to afford the title compound (86 mg); MS (ES+) m/e 379 [M+H]+.

Workup

  1. temperatureto warm to room temperature over 40 minutes
  2. temperatureheated at 80° C. for 2.5 hours
  3. temperatureto cool to room temperature
  4. washwashed with methanol
  5. additiona mixture of 0.880 ammonia/methanol (1:9)
  6. concentrationconcentrated in vacuo
  7. customresulting residue
  8. customwas purified by column chromatography
  9. washeluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.2:1.8:98)

Sources & evidence

ORD record
ord-c96f7e16b1574460b7231890376b93b7
Source dataset
uspto-grants-2012_06
Patent number
US08207331B2

Reaction notes

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