Sodium hydride → 1,1-Dimethylethyl 7-Iodo-8-({5-[(methylamino)carbonyl]-2-pyridinyl}oxy)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate

HRID 222657Notes

Reaction equation

[H-].[Na+].[OH:3][C:4]1[C:21]([I:22])=[CH:20][C:7]2[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:11][CH2:12][C:6]=2[CH:5]=1.Cl[C:24]1[CH:33]=[CH:32][C:27]([C:28]([NH:30][CH3:31])=[O:29])=[CH:26][N:25]=1>CS(C)=O.O.ClCCl>[I:22][C:21]1[C:4]([O:3][C:24]2[CH:33]=[CH:32][C:27]([C:28]([NH:30][CH3:31])=[O:29])=[CH:26][N:25]=2)=[CH:5][C:6]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:17])[CH3:18])=[O:14])[CH2:9][CH2:8][C:7]=2[CH:20]=1

Participants

Conditions

Temperature: 100 °C

Procedure

Sodium hydride (60% disp. in mineral oil, 240 mg, 6 mmol) was added to a stirred solution of 1,1-dimethylethyl 7-hydroxy-8-iodo-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (D41) (1.94 g, 5 mmol) in dimethyl sulfoxide (10 ml). After 10 minutes, 6-chloro-N-methyl-nicotinamide (D10) (850 mg, 5 mmol) was added and the reaction mixture was heated to 100° C. for 20 hours. After cooling to room temperature the reaction mixture was diluted with water and dichloromethane. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (1:1 ethyl acetate:hexanes) to afford the title product (D42).

Workup

temperatureAfter cooling to room temperature the reaction mixture
customThe organic layer was separated
washwashed with water and brine
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography (1:1 ethyl acetate:hexanes)

Sources & evidence

ORD record: ord-8234445738234248983b19b35c78564b
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08207331B2

Reaction notes

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