Cesium carbonate → 6-[(6-tert-butylthiomethyl-pyridin-3-ylmethyl)-amino]-7-chloro-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1191118Notes

Reaction equation

HRID 1191118 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[N:5][C:6]([CH2:9][S:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:7][CH:8]=1.[Cl:15][C:16]1[CH:32]=[CH:31][C:19]2[CH2:20][CH2:21][N:22]([C:25](=[O:30])[C:26]([F:29])([F:28])[F:27])[CH2:23][CH2:24][C:18]=2[C:17]=1OS(C(F)(F)F)(=O)=O.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+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[C:11]([S:10][CH2:9][C:6]1[N:5]=[CH:4][C:3]([CH2:2][NH:1][C:17]2[C:18]3[CH2:24][CH2:23][N:22]([C:25](=[O:30])[C:26]([F:28])([F:27])[F:29])[CH2:21][CH2:20][C:19]=3[CH:31]=[CH:32][C:16]=2[Cl:15])=[CH:8][CH:7]=1)([CH3:14])([CH3:13])[CH3:12]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 584954543-Aminomethyl-6-(tert-butylthio)methyl-pyridine

Product 1

HCID 866241646-[(6-tert-butylthiomethyl-pyridin-3-ylmethyl)-amino]-7-chloro-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 71%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

Use a method similar to the General Procedure 1-3. Add 3-aminomethyl-6-(tert-butylthio)methyl-pyridine (2.99 g, 14.2 mmol), 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (5.05 g, 11.9 mmol), tris(dibenzylideneacetone)dipalladium(0) (275 mg, 0.3 mmol), palladium(II) acetate (133 mg, 0.6 mmol), BINAP (560 mg, 0.9 mmol) and cesium carbonate (5.82 g, 17.9 mmol) to toluene (100 mL) under a nitrogen atmosphere. Heat the mixture at 90° C. for 12 h. Cool the mixture to room temperature. Purify by chromatography on silica gel eluting with hexane/EtOAc (100:0 to 85:15 gradient) to obtain 6-[(6-tert-butylthiomethyl-pyridin-3-ylmethyl)-amino]-7-chloro-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (4.1 g, 71%). MS (APCI+) m/z: 486 (M+H)+.

Workup

  1. temperatureCool the mixture to room temperature
  2. customPurify by chromatography on silica gel eluting with hexane/EtOAc (100:0 to 85:15 gradient)

Sources & evidence

ORD record
ord-45fc77dbb78646b89ea6e3dc9997c05e
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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