Potassium Phosphate, Tribasic → HCID 66706552, compound

HRID 2041290Notes

Reaction equation

HRID 2041290 reaction equation
[Cl:1][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.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH3:56][C:57]1[O:63][C:60]([CH2:61][NH2:62])=[CH:59][CH:58]=1>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]>[ClH:1].[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][NH:8][CH2:9][CH2:10][C:4]=2[C:3]=1[NH:62][CH2:61][C:60]1[O:63][C:57]([CH3:56])=[CH:58][CH:59]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27246835-Methyl-2-furylmethylamineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 66706552HCID 66706552, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
90 °C

Procedure

Combine 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (100 mg, 0.24 mmol), 2-(di-tert-butylphosphino)-biphenyl (6.8 mg, 0.023 mmol), tris(dibenzylideneacetone)dipalladium (11 mg, 0.012 mmol) and potassium phosphate (70 mg, 0.33 mmol) in a pressure tube and degas. Dissolve the mixture in dry toluene (2 mL) and degas. Add a solution of 5-methylfurfurylamine (30 mg, 0.27 mmol) in toluene (1 mL) and degas. Stir at 90° C. for 24h. Cool to ambient temperature, dilute with ethyl ether and filter through Celite®. Concentrate and purify by chromatography on silica gel eluting with hexane/EtOAc (20:1). Remove the solvent and add 7M ammonia in methanol (4 mL). Stir at ambient temperature for 24 h. Concentrate and purify by SCX chromatography to give the free base of the title compound. Use a method similar to the General Procedure 2-2 to obtain the title compound as a solid (56 mg, 66%). MS (ES+) m/z: 291 (M+H)+.

Workup

  1. customdegas
  2. customdegas
  3. temperatureCool to ambient temperature
  4. additiondilute with ethyl ether
  5. filtrationfilter through Celite®
  6. concentrationConcentrate
  7. custompurify by chromatography on silica gel eluting with hexane/EtOAc (20:1)
  8. customRemove the solvent
  9. additionadd 7M ammonia in methanol (4 mL)
  10. stirringStir at ambient temperature for 24 h
  11. concentrationConcentrate
  12. custompurify by SCX chromatography

Sources & evidence

ORD record
ord-21c90eacc8a445489e0aa4f29469227a
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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