Sodium hydride → 5-(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxy)-pyrazine-2-carboxylic acid methyl ester

HRID 222690Notes

Reaction equation

HRID 222690 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.[CH3:19][O:20][C:21]([C:23]1[CH:28]=[N:27][C:26](Cl)=[CH:25][N:24]=1)=[O:22]>CN(C)C=O.ClCCl>[CH3:19][O:20][C:21]([C:23]1[CH:28]=[N:27][C:26]([O:18][C:15]2[CH:16]=[CH:17][C:10]3[CH2:9][CH2:8][N:7]([CH:3]4[CH2:6][CH2:5][CH2:4]4)[CH2:13][CH2:12][C:11]=3[CH:14]=2)=[CH:25][N:24]=1)=[O:22]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 406081Methyl 5-chloropyrazine-2-carboxylateHCID 100820813-Cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[D]azepin-7-OL

Product 1

HCID 104732785-(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxy)-pyrazine-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Sodium hydride (60% disp. in mineral oil, 332 mg, 8.3 mmol) was added to a stirred solution of 3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ol (E3) (1.64 g, 7.5 mmol) in dimethyl formamide (4 ml). After 0.5 hours, a solution of 5-chloro-pyrazine-2-carboxylic acid methyl ester (1.95 g, 11.3 mmol) in dimethyl formamide (8 ml) was added and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with dichloromethane and the organic layer was washed with water, brine and dried over magnesium sulfate. The organic layer was filtered, concentrated in vacuo and the resulting residue was purified by column chromatography eluting with a mixture of 0.880 ammonia:ethanol:dichloromethane (1:9:90) to afford the title compound (E122). MS (ES+) m/e 354 [M+H]+.

Workup

  1. washthe organic layer was washed with water, brine
  2. dry with materialdried over magnesium sulfate
  3. filtrationThe organic layer was filtered
  4. concentrationconcentrated in vacuo
  5. customthe resulting residue was purified by column chromatography
  6. washeluting with a mixture of 0.880 ammonia:ethanol:dichloromethane (1:9:90)

Sources & evidence

ORD record
ord-9a7cb34e6b3f42b9a7411d76bea5e3b4
Source dataset
uspto-grants-2012_06
Patent number
US08207331B2

Reaction notes

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