N,N'-Dimethylethylenediamine → 1-{5-[(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-2-pyrazinyl}-2-pyrrolidinone

HRID 645877Notes

Reaction equation

Cl[C:2]1[N:3]=[CH:4][C:5]([O:8][C:9]2[CH:23]=[CH:22][C:12]3[CH2:13][CH2:14][N:15]([CH:18]4[CH2:21][CH2:20][CH2:19]4)[CH2:16][CH2:17][C:11]=3[CH:10]=2)=[N:6][CH:7]=1.[NH:24]1[CH2:28][CH2:27][CH2:26][C:25]1=[O:29].C(=O)([O-])[O-].[K+].[K+].CNCCNC>O1CCOCC1.CO.[Cu]I>[CH:18]1([N:15]2[CH2:14][CH2:13][C:12]3[CH:22]=[CH:23][C:9]([O:8][C:5]4[N:6]=[CH:7][C:2]([N:24]5[CH2:28][CH2:27][CH2:26][C:25]5=[O:29])=[N:3][CH:4]=4)=[CH:10][C:11]=3[CH2:17][CH2:16]2)[CH2:21][CH2:20][CH2:19]1

Participants

Conditions

Temperature: 175 °C

Procedure

7-[(5-Chloro-2-pyrazinyl)oxy]-3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepine (E257) (132 mg, 0.40 mmol), pyrrolidinone (0.06 ml, 0.80 mmol), potassium carbonate (200 mg, 1.45 mmol), copper (I) iodide (23 mg, 0.12 mmol) and N,N′-dimethylethylenediamine (0.01 ml, 0.12 mmol) were added together in dry dioxane (3 ml) and heated in a microwave reactor at 175° C. for 30 minutes. The mixture was diluted with methanol 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 the 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 (64 mg); MS (ES+) m/e 379 [M+H]+.

Workup

washwashed with methanol
additiona mixture of 0.880 ammonia/methanol (1:9)
concentrationconcentrated in vacuo
customthe resulting residue was purified by column chromatography
washeluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.2:1.8:98)

Sources & evidence

ORD record: ord-48694934d3f54bb38bd9f079cffbaaad
Source dataset: uspto-grants-2010_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07704994B2

Reaction notes

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