Cesium carbonate → HCID 86629675, compound

HRID 2041538Notes

Reaction equation

HRID 2041538 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][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([C:35](=[O:41])[CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[CH:31][C:30]=1[Cl:42].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]>[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]=1[NH:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([C:35](=[O:41])[CH2:36][C:37]([CH3:38])([CH3:39])[CH3:40])=[CH:31][C:30]=1[Cl:42]

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 576559541-[4-(Aminomethyl)-3-chlorophenyl]-3,3-dimethyl-1-butanone

Product 1

HCID 86629675HCID 86629675, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Use a method similar to the General Procedure 5-2 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (300 mg, 0.71 mmol) with 1-(4-aminomethyl-3-chloro-phenyl)-3,3-dimethyl-butan-1-one (338 mg, 1.41 mmol) by using tris(dibenzylideneacetone)dipalladium(0) (130 mg, 0.142 mmol), BINAP (177 mg, 0.284 mmol) and cesium carbonate (324 mg, 0.994 mmol) in anhydrous toluene (31 mL). Purify by chromatography on silica gel eluting with hexane/EtOAc (92:8) followed by reverse phase HPLC [Hichrom Kromasil C18, 5 □M 21.2×100 mm, eluting with water/acetonitrile (0.05% TFA in each) (1:4 to 1:19 gradient over 5 min), flow rate 25 mL/min, UV detector (230 nm)] to give 7-chloro-6-[2-chloro-4-(3,3-dimethyl-butyryl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as an oil (77 mg, 21%). MS (ES+) m/z: 516 (M+H)+.

Workup

  1. customPurify by chromatography on silica gel eluting with hexane/EtOAc (92:8)
  2. washeluting with water/acetonitrile (0.05% TFA in each) (1:4 to 1:19 gradient over 5 min), flow rate 25 mL/min, UV detector (230 nm)]

Sources & evidence

ORD record
ord-3a81545f8c774fde991a6cba3153b341
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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