Ammonia → 1-(3-Bromo-4-ethyl-anilino)-4-[2-(2-chloro-pyridin-4-yl)ethyl]-isoquinoline

HRID 2252846Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][C:27]=1[CH2:28][CH3:29])[NH:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][N:21]=[C:20](O)[CH:19]=2)=[CH:8][N:7]=1.P(Cl)(Cl)([Cl:32])=O.Cl.N>C(#N)C.O1CCOCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][C:27]=1[CH2:28][CH3:29])[NH:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][N:21]=[C:20]([Cl:32])[CH:19]=2)=[CH:8][N:7]=1

Participants

Conditions

Temperature: 65 °C

Procedure

Under a N2 atmosphere, 150 mg (0.334 mmol) of 1-(3-bromo-4-ethyl-anilino)-4-[2-(2-hydroxy-pyridin-4-yl)-ethyl]-isoquinoline (Ex. 32a) in 5 ml of acetonitrile are mixed with 76 μl (0.83 mmol) of phosphorus oxychloride and 0.17 ml (0.68 mmol) of 4 N HCl in dioxane, and stirred at 65° C. A further 76 μl of phosphorus oxychloride is added after 12 h, and stirring continues for 48 h at 65° C. The mixture is cooled to RT, 4 ml of 10% NH3 solution added, and it is partitioned between 3 portions of EtOAc, 2 portions of water and brine. Drying (Na2SO4), concentrating by evaporation and chromatography on silica gel (acetone/methylene chloride 3:2) yield 1-(3-bromo-4-ethyl-anilino)-4-[2-(2-chloro-pyridin-4-yl)ethyl]-isoquinoline; FAB-MS: (M+H)+=466/468; HPLC(gradient20-100) tRef=13.4.

Workup

stirringstirring
temperatureThe mixture is cooled to RT
customit is partitioned between 3 portions of EtOAc, 2 portions of water and brine
dry with materialDrying (Na2SO4)
concentrationconcentrating by evaporation and chromatography on silica gel (acetone/methylene chloride 3:2)

Sources & evidence

ORD record: ord-3d9e43ed94b6491d82e3e01468c80a7f
Source dataset: uspto-grants-2008_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07323474B2

Reaction notes

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