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

HRID 1750681Notes

Reaction equation

HRID 1750681 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:7][CH2:6][CH2:5][C@@H:4]1[NH:8][C:9](=[O:22])[C:10]1[CH:15]=[C:14]([Cl:16])[CH:13]=[CH:12][C:11]=1[N:17]1[N:21]=[CH:20][CH:19]=[N:18]1.Br[C:24]1[CH:29]=[CH:28][C:27]([O:30][C:31]([F:34])([F:33])[F:32])=[CH:26][N:25]=1.CC(C)([O-])C.[K+].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>C1(C)C=CC=CC=1.O.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]>[Cl:16][C:14]1[CH:13]=[CH:12][C:11]([N:17]2[N:18]=[CH:19][CH:20]=[N:21]2)=[C:10]([CH:15]=1)[C:9]([NH:8][C@H:4]1[CH2:5][CH2:6][CH2:7][C@@H:3]1[NH:2][C:24]1[CH:29]=[CH:28][C:27]([O:30][C:31]([F:32])([F:34])[F:33])=[CH:26][N:25]=1)=[O:22]

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 23665647Potassium tert-butoxideHCID 457896272-Bromo-5-(trifluoromethoxy)pyridineHCID 118308315N-[(1S,2S)-2-Aminocyclopentyl]-5-chloro-2-(2H-1,2,3-triazol-2-yl)benzamide hydrochloride2×

Product 1

HCID 1183082105-Chloro-2-(2H-1,2,3-triazol-2-yl)-N-[(1S,2S)-2-{[5-(trifluoromethoxy)pyridin-2-yl]amino}cyclopentyl]benzamide

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of N-[(1S,2S)-2-aminocyclopentyl]-5-chloro-2-(2H-1,2,3-triazol-2-yl)benzamide hydrochloride (Intermediate 31; 120 mg, 0.35 mmol), 2-bromo-5-(trifluoromethoxy)pyridine (CAS number 888327-36-4; 127 mg, 0.53 mmol) and potassium tert-butoxide (118 mg, 1.05 mmol) in toluene (10 ml) was degassed under a nitrogen atmosphere for 15 minutes. To this was then added BINAP (22 mg, 0.035 mmol) and tris(dibenzylideneacetone)dipalladium(0) (32 mg, 0.035 mmol) and the reaction mixture was again degassed for 15 minutes. The reaction mixture was heated at 120° C. for 15 hours and then was diluted with water, filtered through diatomaceous earth (commercially sold under the trade mark “Celite”) and extracted with ethyl acetate. The organics were washed with water, brine, dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica, 0-2.5% methanol/DCM) to afford the title compound.

Workup

  1. filtrationfiltered through diatomaceous earth (
  2. extractionextracted with ethyl acetate
  3. washThe organics were washed with water, brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by column chromatography (silica, 0-2.5% methanol/DCM)

Sources & evidence

ORD record
ord-0638dc1f9a9e441bb3c9ae868f39e876
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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