2-Bromo-5-nitrothiazole → 3-Cyclobutyl-7-[(5-nitro-1,3-thiazol-2-yl)oxy]-2,3,4,5-tetrahydro-1H-3-benzazepine

HRID 222708

Reaction equation

HRID 222708 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[S:21][C:22]([N+:25]([O-:27])=[O:26])=[CH:23][N:24]=1>CN(C)C=O.C(OCC)(=O)C>[CH:3]1([N:7]2[CH2:8][CH2:9][C:10]3[CH:17]=[CH:16][C:15]([O:18][C:20]4[S:21][C:22]([N+:25]([O-:27])=[O:26])=[CH:23][N:24]=4)=[CH:14][C:11]=3[CH2:12][CH2:13]2)[CH2:6][CH2:5][CH2:4]1

Participants

6

Reactant 3

HCID 182112-Bromo-5-nitrothiazoleHCID 24758Sodium hydrideHCID 100820813-Cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[D]azepin-7-OL

Product 1

HCID 103376233-Cyclobutyl-7-[(5-nitro-1,3-thiazol-2-yl)oxy]-2,3,4,5-tetrahydro-1H-3-benzazepine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (60% disp. in mineral oil, 150 mg, 3.66 mmol) was added to a stirred solution of 3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ol (E3) (530 mg, 2.43 mmol) in dimethylformamide (10 ml) at 5° C. After 0.5 hours a solution of 2-bromo-5-nitro-1,3-thiazole (1.0 g, 4.78 mmol) in dimethylformamide (5 ml) was added and the reaction mixture was allowed to warm to room temperature and stir for 2 hours. The reaction mixture was diluted with ethyl acetate and the organic layer was washed with water, brine, dried (sodium sulfate) and concentrated in vacuo. Purification by column chromatography eluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.25:2.25:97.5) afforded the title compound (E210a); MS (ES+) m/e 346 [M+H]+.

Workup

  1. washthe organic layer was washed with water, brine
  2. dry with materialdried (sodium sulfate)
  3. concentrationconcentrated in vacuo
  4. customPurification by column chromatography
  5. washeluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.25:2.25:97.5)

Sources & evidence

ORD record
ord-01537a48dcc649d4a65f657d63062397
Source dataset
uspto-grants-2012_06
Patent number
US08207331B2

Linked notes

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