Cesium carbonate → HCID 86629680, compound

HRID 2041543Notes

Reaction equation

HRID 2041543 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:43]=[CH:42][C:32]([C:33]([NH:35][C@H:36]([CH3:41])[C:37]([F:40])([F:39])[F:38])=[O:34])=[C:31]([F:44])[CH:30]=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:13])([F:15])[F:14])[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:27][CH2:28][C:29]1[CH:43]=[CH:42][C:32]([C:33](=[O:34])[NH:35][C@H:36]([CH3:41])[C:37]([F:39])([F:40])[F:38])=[C:31]([F:44])[CH:30]=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 57655921HCID 57655921, compound

Product 1

HCID 86629680HCID 86629680, compoundYield 62.4%

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 (0.561 g, 1.319 mmol) with (R)-4-aminomethyl-2-fluoro-N-(2,2,2-trifluoro-1-methyl-ethyl)-benzamide (0.698 g, 2.642 mmol) by using tris(dibenzylideneacetone)dipalladium(0) (0.241 g, 0.264 mmol), BINAP (0.33 g, 0.53 mmol) and cesium carbonate (1.51 g, 4.63 mmol) in anhydrous toluene (13 mL). Purify by chromatography on silica gel (40g RediSep® column) eluting with hexane/EtOAc (19:1 to 1:1 gradient over 30 min; 35 mL/min) and then by SCX chromatography to afford (R)-7-chloro-6-[3-fluoro-4-(2,2,2-trifluoro-1-methyl-ethylcarbamoyl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a colorless oil (0.444g, 62%). MS (ES+) m/z: 540.1 (M+H)+.

Workup

  1. customPurify by chromatography on silica gel (40g RediSep® column)
  2. washeluting with hexane/EtOAc (19:1 to 1:1 gradient over 30 min; 35 mL/min)

Sources & evidence

ORD record
ord-6d18d53008de4f9c9b1bbeffdaca8762
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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