Cesium carbonate → 2,3,4,5-Tetrahydro-1H-benzo(d)azepine

HRID 1191155Notes

Reaction equation

HRID 1191155 reaction equation
Cl[C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8](C(=O)C(F)(F)F)[CH2:9][CH2:10][C:4]=2[C:3]=1OS(C(F)(F)F)(=O)=O.C1(CN2C=CC(C3C=CC(CN)=CC=3)=N2)CC1.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.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]>[CH2:10]1[C:4]2[CH:3]=[CH:2][CH:18]=[CH:17][C:5]=2[CH2:6][CH2:7][NH:8][CH2:9]1

Participants

7

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 58495574HCID 58495574, compound

Product 1

HCID 14002432,3,4,5-Tetrahydro-1H-benzo(d)azepineYield 203.8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Use a method similar to the General Procedure 1-2 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (193 mg, 0.45 mmol) with 4-(1-cyclopropylmethyl-1H-pyrazol-3-yl)-benzylamine (207 mg, 0.91 mmol) using tris(dibenzylideneacetone)dipalladium(0) (83 mg, 0.091 mmol), BINAP (113 mg, 0.182 mmol) and cesium carbonate (207 mg, 0.627 mmol) in toluene (21 mL). Purify by chromatography on silica gel eluting with hexane:EtOAc (9:1) to give 7-chloro-6-[4-(1-cyclopropylmethyl-1H-pyrazol-3-yl)-benzylamino]trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a yellow oil (135 mg, 59%). MS (ES+) m/z: 503 (M+H)+.

Workup

  1. customPurify by chromatography on silica gel eluting with hexane:EtOAc (9:1)

Sources & evidence

ORD record
ord-11b373b536c943b48cdb9d57dc74e6d4
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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