Potassium Carbonate → tert-Butyl N-[(1S,2S)-2-{[3-cyclopropyl-5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]carbamate

HRID 1750567Notes

Reaction equation

HRID 1750567 reaction equation
Br[C:2]1[C:3]([NH:12][C@H:13]2[CH2:17][CH2:16][CH2:15][C@@H:14]2[NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:7]=1.[CH:26]1(B(O)O)[CH2:28][CH2:27]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:26]1([C:2]2[C:3]([NH:12][C@H:13]3[CH2:17][CH2:16][CH2:15][C@@H:14]3[NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:7]=2)[CH2:28][CH2:27]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 118308064tert-butyl ((1S,2S)-2-((3-bromo-5-(trifluoromethyl)pyrazin-2-yl)amino)cyclopentyl)carbamate

Product 1

HCID 118308262tert-Butyl N-[(1S,2S)-2-{[3-cyclopropyl-5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]carbamate

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A suspension of tert-butyl N-[(1S,2S)-2-{[3-bromo-5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]carbamate (2.44 g, 5.73 mmol), cyclopropylboronic acid (2.46 g, 28.6 mmol), potassium carbonate (3.17 g, 22.9 mmol) and tetrakis(triphenylphosphine)palladium (0.662 g, 0.57 mmol) in 1,4-dioxane (15 ml) and water (4 ml) was subjected to microwave irradiation at 140° C. for 2 hours. The reaction was partitioned between ethyl acetate (20 ml) and water (20 ml). The aqueous layer was extracted with ethyl acetate (2×50 ml) and combined organics were washed with brine (50 ml), filtered through a hydrophobic frit and concentrated in vacuo. The crude product was purified by column chromatography (silica, 0-50% ethyl acetate/petrol) to afford the title compound.

Workup

  1. customirradiation at 140° C. for 2 hours
  2. customThe reaction was partitioned between ethyl acetate (20 ml) and water (20 ml)
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×50 ml)
  4. washcombined organics were washed with brine (50 ml)
  5. filtrationfiltered through a hydrophobic frit
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography (silica, 0-50% ethyl acetate/petrol)

Sources & evidence

ORD record
ord-576dd6495d4140a698c64458db474eb3
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

Loading…