Binap, (A+-)- → 2-(2H-1,2,3-Triazol-2-yl)-N-[(1S,2S)-2-{[5-(trifluoromethoxy)pyridin-2-yl]amino}cyclopentyl]benzamide

HRID 1750680Notes

Reaction equation

HRID 1750680 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:7][CH2:6][CH2:5][C@@H:4]1[NH:8][C:9](=[O:21])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[N:16]1[N:20]=[CH:19][CH:18]=[N:17]1.Br[C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[CH:25][N:24]=1.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.CC(C)([O-])C.[Na+]>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]>[N:20]1[N:16]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[C:9]([NH:8][C@H:4]2[CH2:5][CH2:6][CH2:7][C@@H:3]2[NH:2][C:23]2[CH:28]=[CH:27][C:26]([O:29][C:30]([F:31])([F:33])[F:32])=[CH:25][N:24]=2)=[O:21])[N:17]=[CH:18][CH:19]=1

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 457896272-Bromo-5-(trifluoromethoxy)pyridineHCID 118025476N-[(1S,2S)-2-Aminocyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide hydrochloride2×

Product 1

HCID 1183081952-(2H-1,2,3-Triazol-2-yl)-N-[(1S,2S)-2-{[5-(trifluoromethoxy)pyridin-2-yl]amino}cyclopentyl]benzamide

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of N-[(1S,2S)-2-aminocyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide hydrochloride (Intermediate 4; 75 mg, 0.24 mmol), 2-bromo-5-(trifluoromethoxy)pyridine (CAS number 888327-36-4; 59 mg, 0.24 mmol), BINAP (15 mg, 0.024 mmol), tris(dibenzylideneacetone)dipalladium(0) (11 mg, 0.012 mmol) and sodium tert-butoxide (33 mg, 0.34 mmol) in dry toluene (2.4 ml) was sealed, evacuated and purged with nitrogen and heated at 110° C. for 17 hours. The reaction was partitioned between ethyl acetate and water, washing with water, brine, filtered through a hydrophobic frit and concentrated in vacuo. The residue was purified by column chromatography (silica, 0-100% ethyl acetate/petrol) to afford the title compound.

Workup

  1. customwas sealed
  2. customevacuated
  3. custompurged with nitrogen
  4. customThe reaction was partitioned between ethyl acetate and water
  5. washwashing with water, brine
  6. filtrationfiltered through a hydrophobic frit
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (silica, 0-100% ethyl acetate/petrol)

Sources & evidence

ORD record
ord-809af118bd094fee88de1be288495d10
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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