Sodium hydride → 1,1-Dimethylethyl 7-({5-[(methyloxy)carbonyl]-2-pyrazinyl}oxy)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate

HRID 222662Notes

Reaction equation

HRID 222662 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:16][CH2:15][C:14]2[CH:17]=[C:18]([OH:21])[CH:19]=[CH:20][C:13]=2[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl[C:23]1[N:24]=[CH:25][C:26]([C:29]([O:31][CH3:32])=[O:30])=[N:27][CH:28]=1>CN(C)C=O>[CH3:32][O:31][C:29]([C:26]1[N:27]=[CH:28][C:23]([O:21][C:18]2[CH:19]=[CH:20][C:13]3[CH2:12][CH2:11][N:10]([C:8]([O:7][C:3]([CH3:6])([CH3:4])[CH3:5])=[O:9])[CH2:16][CH2:15][C:14]=3[CH:17]=2)=[N:24][CH:25]=1)=[O:30]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 406081Methyl 5-chloropyrazine-2-carboxylateHCID 18173274tert-butyl 7-hydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine-3-carboxylate

Product 1

HCID 589845771,1-Dimethylethyl 7-({5-[(methyloxy)carbonyl]-2-pyrazinyl}oxy)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylateYield 58.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
5 °C

Procedure

Sodium hydride (60% dispersion in mineral oil) (6.4 g, 0.16 mol) was added portionwise to a solution of 7-hydroxy-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid tert-butyl ester (PCT Int. Appl. (2002), WO 02/40471) (40 g, 0.15 mol) in dry dimethylformamide (200 ml) cooled to 5° C. over 15 minutes. After 15 minutes, the mixture was allowed to warm to room temperature and stirred for 60 minutes. The mixture was cooled in an ice-water bath and methyl 5-chloro-2-pyrazinecarboxylate (31.2 g, 0.18 mol) was added portionwise. The mixture was allowed to warm to room temperature and stirred for 18 hours. The mixture was poured onto water (500 ml) and ice (500 ml) and stirred until the ice had melted. The resulting solid was collected by filtration, washed with water and dissolved in ethyl acetate (1500 ml). The ethyl acetate layer was washed with brine (200 ml), dried under sodium sulfate and evaporated in vacuo. The crude product was purified by column chromatography eluting with a mixture of ethyl acetate:hexane (1:2) to afford the title compound (35.07 g).

Workup

  1. temperatureto warm to room temperature
  2. temperatureThe mixture was cooled in an ice-water bath
  3. temperatureto warm to room temperature
  4. stirringstirred for 18 hours
  5. filtrationThe resulting solid was collected by filtration
  6. washwashed with water
  7. dissolutiondissolved in ethyl acetate (1500 ml)
  8. washThe ethyl acetate layer was washed with brine (200 ml)
  9. customdried under sodium sulfate
  10. customevaporated in vacuo
  11. customThe crude product was purified by column chromatography
  12. washeluting with a mixture of ethyl acetate:hexane (1:2)

Sources & evidence

ORD record
ord-7239690212804fcf99c9f0be967e72d6
Source dataset
uspto-grants-2012_06
Patent number
US08207331B2

Reaction notes

Loading…