Cesium carbonate → (+/-)-7-chloro-6-[1-(5-methylthiophen-2-yl)ethylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 2041288Notes

Reaction equation

HRID 2041288 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1OS(C(F)(F)F)(=O)=O.[NH2:27][CH:28]([C:30]1[S:31][C:32]([CH3:35])=[CH:33][CH:34]=1)[CH3:29].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:13])[F:14])[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:27][CH:28]([C:30]1[S:31][C:32]([CH3:35])=[CH:33][CH:34]=1)[CH3:29]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 42794271-(5-Methylthiophen-2-yl)ethan-1-amineHCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 86629641(+/-)-7-chloro-6-[1-(5-methylthiophen-2-yl)ethylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 50%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

Use a method similar to the General Procedure 5-1 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (96 mg, 0.227 mmol) with (±)-2-(1-aminoethyl)-5-methylthiophene (48 mg, 0.34 mmol) using palladium(II) acetate (10 mg, 0.0454 mmol), BINAP (60 mg, 0.0908 mmol) and cesium carbonate (148 mg, 0.454 mmol) in toluene (10 mL). Purify by chromatography on silica gel eluting with hexane/EtOAc (1:0, 19:1) to give (±)-7-chloro-6-[1-(5-methylthiophen-2-yl)ethylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as an oil (47 mg, 50%). GC-MS m/z 416 (M+).

Workup

  1. customPurify by chromatography on silica gel eluting with hexane/EtOAc (1:0, 19:1)

Sources & evidence

ORD record
ord-f1eb5f1d7c6f4dbda8120ccd7867d7c7
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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