Cesium carbonate → HCID 86658974, compound

HRID 1191114Notes

Reaction equation

HRID 1191114 reaction equation
Cl.[CH3:2][NH:3][C:4]1[O:5][CH:6]=[C:7]([C:9]2[CH:16]=[CH:15][C:12]([CH2:13][NH2:14])=[CH:11][CH:10]=2)[N:8]=1.[Cl:17][C:18]1[CH:34]=[CH:33][C:21]2[CH2:22][CH2:23][N:24]([C:27](=[O:32])[C:28]([F:31])([F:30])[F:29])[CH2:25][CH2:26][C:20]=2[C:19]=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+]>C1(C)C=CC=CC=1.CN(C=O)C.CCOC(C)=O.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:17][C:18]1[CH:34]=[CH:33][C:21]2[CH2:22][CH2:23][N:24]([C:27](=[O:32])[C:28]([F:29])([F:31])[F:30])[CH2:25][CH2:26][C:20]=2[C:19]=1[NH:14][CH2:13][C:12]1[CH:15]=[CH:16][C:9]([C:7]2[N:8]=[C:4]([NH:3][CH3:2])[O:5][CH:6]=2)=[CH:10][CH:11]=1

Participants

9

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 67463701HCID 67463701, compound

Product 1

HCID 86658974HCID 86658974, compoundYield 20%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

Slurry 4-(2-methylamino-oxazol-4-yl)-benzylamine hydrochloride (485 mg, 1.8 mmol) in toluene (10 mL) and DMF (1 mL) at 90° C. under a nitrogen atmosphere. Degass and place under vacuum then purge with nitrogen three times. Add 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0:5 g, 1.17 mmol), tris(dibenzylideneacetone)dipalladium(0) (161 mg, 0.18 mmol), BINAP (219 mg, 0.35 mmol) and cesium carbonate (1.6 g, 4.9 mmol) to the slurry at 90° C. Stir the mixture at 95° C. for 16 h in a sealed flask. Cool the reaction to room temperature, dilute with EtOAc (100 mL), filter through Celite®, and concentrate in vacuo to an oil. Purify by chromatography on silica gel (10 g, pre-packed cartridge) eluting with hexane/THF (40:1 to 4:1 gradient) followed by SCX chromatography (10 g) eluting with DCM and DCM/2M ammonia in methanol (1:1, 50 mL) to obtain 7-chloro-6-[4-(2-methylamino-oxazol-4-yl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (110 mg, 20%). MS (ES+) m/z: 479.2 (M+H)+.

Workup

  1. customat 90° C.
  2. customDegass
  3. customplace under vacuum then purge with nitrogen three times
  4. customat 90° C
  5. temperatureCool
  6. customthe reaction to room temperature
  7. filtrationfilter through Celite®
  8. concentrationconcentrate in vacuo to an oil
  9. customPurify by chromatography on silica gel (10 g, pre-packed cartridge)
  10. washeluting with hexane/THF (40:1 to 4:1 gradient)
  11. washeluting with DCM and DCM/2M ammonia in methanol (1:1, 50 mL)

Sources & evidence

ORD record
ord-d23b93206cc3481d9ae7e78e07b26918
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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