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 911403Notes

Reaction equation

HRID 911403 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-88fe6b22415a4422b451363729e55d7d
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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