7-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine → HCID 59787411, compound

HRID 1965981Notes

Reaction equation

HRID 1965981 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.[CH2:27]([NH:32][C:33]([CH:35]1[CH2:39][CH2:38][CH2:37][CH2:36]1)=[O:34])[CH2:28][CH2:29][C:30]#[CH:31]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cu](I)I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(N(CC)CC)C>[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[C:31]#[C:30][CH2:29][CH2:28][CH2:27][NH:32][C:33]([CH:35]1[CH2:39][CH2:38][CH2:37][CH2:36]1)=[O:34]

Participants

7

Reactant 2

HCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 59787428HCID 59787428, compound

Product 1

HCID 59787411HCID 59787411, compoundYield 68%

Reagents, catalysts & solvents 4

HCID 67553Tetrabutylammonium IodideCatalystHCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

In an oven dried flask degas DMF (20 mL) by gently bubbling nitrogen gas for 2 h. Add then 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (1.0 g, 2.35 mmoles), N-pent-4-ynyl-cyclopentylcarboxamide (842 mg, 4.7 mmoles), copper iodide (134 mg, 0.705 mmoles), triethylamine (4.7 mL), tetra-n-butylammonium iodide (2.6 g, 7.05 mmoles) and bis(triphenylphosphine)palladium(II) chloride (165 mg, 0.235 mmoles) and heat the resulting mixture at 80° C. under nitrogen atmosphere while stirring overnight. Concentrate the mixture in vacuo, and then filter through a short pad of Celite® eluting with EtOAc. Purify the residue by chromatography on silica gel eluting with dichloromethane/EtOAc/cyclohexane (3:5:1) to obtain the desired intermediate as an oil (726 mg, 68%). MS (ES+) m/z=455.1 (M+H)+.

Workup

  1. customIn an oven dried flask
  2. customdegas DMF (20 mL) by gently bubbling nitrogen gas for 2 h
  3. additionAdd
  4. concentrationConcentrate the mixture in vacuo
  5. filtrationfilter through a short pad of Celite®
  6. washeluting with EtOAc
  7. customPurify the residue by chromatography on silica gel eluting with dichloromethane/EtOAc/cyclohexane (3:5:1)

Sources & evidence

ORD record
ord-42270e7736b044f8a66eabf38b7c99e2
Source dataset
uspto-grants-2013_04
Patent number
US08420631B2

Reaction notes

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