Cesium carbonate → 3-Cyclobutyl-7-{[6-methyl-4-(methyloxy)-2-quinolinyl]oxy}-2,3,4,5-tetrahydro-1H-3-benzazepine

HRID 222727Notes

Reaction equation

[CH:1]1([N:5]2[CH2:11][CH2:10][C:9]3[CH:12]=[C:13]([OH:16])[CH:14]=[CH:15][C:8]=3[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.Cl[C:18]1[CH:27]=[C:26]([O:28][CH3:29])[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([CH3:30])[CH:24]=2)[N:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH:1]1([N:5]2[CH2:6][CH2:7][C:8]3[CH:15]=[CH:14][C:13]([O:16][C:18]4[CH:27]=[C:26]([O:28][CH3:29])[C:25]5[C:20](=[CH:21][CH:22]=[C:23]([CH3:30])[CH:24]=5)[N:19]=4)=[CH:12][C:9]=3[CH2:10][CH2:11]2)[CH2:4][CH2:3][CH2:2]1

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ol (E3) (58 mg, 0.267 mmol), 2-chloro-6-methyl-4-(methyloxy)quinoline (WO 99/55677) (56 mg, 0.027 mmol) and cesium carbonate (260 mg, 0.801 mmol) in dry DMF (3 ml) was heated at 150° C. for 2×30 mins. (300 W) in a microwave reactor. The cooled reaction mixture was partitioned between ethyl acetate (3×20 ml) and water (30 ml). The combined organic layers were washed with brine (2×30 ml), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the resulting residue by column chromatography on silica gel, eluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.5:4.5:95) to afford the title compound (E227); MS (ES+) m/e 389 [M+H]+.

Workup

customThe cooled reaction mixture
customwas partitioned between ethyl acetate (3×20 ml) and water (30 ml)
washThe combined organic layers were washed with brine (2×30 ml)
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customPurification of the resulting residue by column chromatography on silica gel
washeluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.5:4.5:95)

Sources & evidence

ORD record: ord-835c6f69cc4249bc8e8a4d785df2c96e
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08207331B2

Reaction notes

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