Cesium carbonate → HCID 86624176, compound

HRID 1191134Notes

Reaction equation

HRID 1191134 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.[CH:27]1([C:30]([NH:32][CH2:33][C:34]2[CH:41]=[CH:40][C:37]([CH2:38][NH2:39])=[CH:36][CH:35]=2)=[O:31])[CH2:29][CH2:28]1.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:39][CH2:38][C:37]1[CH:40]=[CH:41][C:34]([CH2:33][NH:32][C:30]([CH:27]2[CH2:28][CH2:29]2)=[O:31])=[CH:35][CH:36]=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 59828864HCID 59828864, compound

Product 1

HCID 86624176HCID 86624176, compoundYield 65%

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 (458 mg, 1.076 mmol) with 4-[(cyclopropanecarbonyl-amino)-methyl]-benzylamine (275 mg, 1.346 mmol) using tris(dibenzylideneacetone)dipalladium(0) (99 mg, 0.108 mmol), BINAP (134 mg, 0.215 mmol) and cesium carbonate (710 mg, 2.17 mmol) in toluene (17 mL). Purify by chromatography on silica gel (80 g, pre-packed cartridge) eluting with hexane/EtOAc (1:0 over 5 min, 49:1 over 5 min, 19:1 over 5 min, 9:1 over 5 min, 85:15 over 5 min, 3:1 over 30 min, 1:1; 50 mL/min) to obtain 7-chloro-6-{4-[(cyclopropanecarbonyl-amino)-methyl]-benzylamino}-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (335 mg, 65%) as a white solid. MS (ES+) m/z: 480 (M+H)+.

Workup

  1. customPurify by chromatography on silica gel (80 g, pre-packed cartridge)
  2. washeluting with hexane/EtOAc (1:0 over 5 min, 49:1 over 5 min, 19:1 over 5 min, 9:1 over 5 min, 85:15 over 5 min, 3:1 over 30 min, 1:1; 50 mL/min)

Sources & evidence

ORD record
ord-ea67e5d6859d4a499befed005a1b2088
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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