Potassium Carbonate → 5-Cyclopropyl-2-(2H-1,2,3-triazol-2-yl)-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]benzamide

HRID 1750624Notes

Reaction equation

HRID 1750624 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]([N:27]2[N:31]=[CH:30][CH:29]=[N:28]2)=[C:6]([CH:26]=1)[C:7]([NH:9][C@H:10]1[CH2:14][CH2:13][CH2:12][C@@H:11]1[NH:15][C:16]1[CH:21]=[N:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][N:17]=1)=[O:8].[CH:32]1(B(O)O)[CH2:34][CH2:33]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.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>[CH:32]1([C:2]2[CH:3]=[CH:4][C:5]([N:27]3[N:31]=[CH:30][CH:29]=[N:28]3)=[C:6]([CH:26]=2)[C:7]([NH:9][C@H:10]2[CH2:14][CH2:13][CH2:12][C@@H:11]2[NH:15][C:16]2[CH:21]=[N:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][N:17]=2)=[O:8])[CH2:34][CH2:33]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 1183082425-Chloro-2-(2H-1,2,3-triazol-2-yl)-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]benzamide

Product 1

HCID 1183082525-Cyclopropyl-2-(2H-1,2,3-triazol-2-yl)-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]benzamide

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 5-chloro-2-(2H-1,2,3-triazol-2-yl)-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]benzamide (Example 52; 100 mg, 0.22 mmol), cyclopropylboronic acid (CAS number 411235-57-9; 29 mg, 0.33 mmol), bis(triphenylphosphine)palladium(II) dichloride (3 mg, 4.43 μmol) and potassium carbonate (31 mg, 0.22 mmol) in 1,4-dioxane (1.3 ml) and water (0.13 ml) was sealed and degassed with nitrogen. The reaction was subjected to microwave irradiation at 130° C. for 30 minutes. To this was then added bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)-dichloropalladium(II) (157 mg, 0.22 mmol) and the reaction was subjected to microwave irradiation at 130° C. for a further 1 hour. The reaction mixture was partitioned between ethyl acetate and water, washed with water and brine, filtered through a hydrophobic frit and concentrated in vacuo. The resulting residue was purified by reverse phase preparative HPLC (eluted with acetonitrile/water containing 0.1% ammonia) to afford the title compound.

Workup

  1. customdegassed with nitrogen
  2. customirradiation at 130° C. for 30 minutes
  3. customirradiation at 130° C. for a further 1 hour
  4. customThe reaction mixture was partitioned between ethyl acetate and water
  5. washwashed with water and brine
  6. filtrationfiltered through a hydrophobic frit
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by reverse phase preparative HPLC (eluted with acetonitrile/water containing 0.1% ammonia)

Sources & evidence

ORD record
ord-d9178259e9dc462cb12c139c74fca749
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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