Sodium hydride → HCID 10452270, compound

HRID 645832Notes

Reaction equation

HRID 645832 reaction equation
[H-].[Na+].[CH:3]1([N:7]2[CH2:13][CH2:12][C:11]3[CH:14]=[C:15]([OH:18])[CH:16]=[CH:17][C:10]=3[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4]1.Br[C:20]1[CH:21]=[N:22][C:23]([N:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)=[N:24][CH:25]=1>N1C=CC=CC=1.[Cu]Br>[CH:3]1([N:7]2[CH2:8][CH2:9][C:10]3[CH:17]=[CH:16][C:15]([O:18][C:20]4[CH:25]=[N:24][C:23]([N:26]5[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]5)=[N:22][CH:21]=4)=[CH:14][C:11]=3[CH2:12][CH2:13]2)[CH2:6][CH2:5][CH2:4]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 36146825-Bromo-2-(piperidin-1-yl)pyrimidineHCID 100820813-Cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[D]azepin-7-OL

Product 1

HCID 10452270HCID 10452270, compound

Reagents, catalysts & solvents 2

HCID 24593copper(I) bromideCatalystHCID 1049PyridineSolvent

Procedure

Sodium hydride (60% disp. in mineral oil, 44 mg, 1.1 mmol) was added to a stirred solution of 3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ol (E3) (200 mg, 0.92 mmol) and copper (I) bromide (184 mg, 1.3 mmol) in pyridine (10 ml) at 0° C. After stirring for 0.5 hour at room temperature, 5-bromo-2-(1-piperidinyl)pyrimidine (D32) (0.669 g, 2.8 mmol) was added and the reaction mixture heated at reflux for 2 hours. The reaction was allowed to cool, filtered and the filtrate was concentrated in vacuo. The crude residue was dissolved with ethyl acetate and washed with water and brine. The organic layer was dried (magnesium sulfate), filtered and concentrated in vacuo. Purification of the resulting residue by column chromatography eluting with a mixture of 0.880 ammonia:ethanol:dichloromethane (0.25:2.25:97.5 to 1:9:90) afforded the title compound (E140). MS (ES+) m/e 379 [M+H]+.

Workup

  1. temperaturethe reaction mixture heated
  2. temperatureat reflux for 2 hours
  3. temperatureto cool
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated in vacuo
  6. dissolutionThe crude residue was dissolved with ethyl acetate
  7. washwashed with water and brine
  8. dry with materialThe organic layer was dried (magnesium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification of the resulting residue by column chromatography
  12. washeluting with a mixture of 0.880 ammonia:ethanol:dichloromethane (0.25:2.25:97.5 to 1:9:90)

Sources & evidence

ORD record
ord-35a2311573be4deab209d6335ee3727b
Source dataset
uspto-grants-2010_04
Patent number
US07704994B2

Reaction notes

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