Ethanamine, 2,2,2-trifluoro- → 2-(4-isopropylphenyl)-N-((1R)-1-{5-[(2,2,2-trifluoroethyl)amino]pyridin-2-yl}ethyl)acetamide

HRID 2383518Notes

Reaction equation

HRID 2383518 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C@H:8]([NH:10][C:11](=[O:22])[CH2:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]([CH3:21])[CH3:20])=[CH:15][CH:14]=2)[CH3:9])=[N:6][CH:7]=1.[F:23][C:24]([F:28])([F:27])[CH2:25][NH2:26].CC([O-])(C)C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)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].C1(C)C=CC=CC=1>[CH:19]([C:16]1[CH:17]=[CH:18][C:13]([CH2:12][C:11]([NH:10][C@@H:8]([C:5]2[CH:4]=[CH:3][C:2]([NH:26][CH2:25][C:24]([F:28])([F:27])[F:23])=[CH:7][N:6]=2)[CH3:9])=[O:22])=[CH:14][CH:15]=1)([CH3:21])[CH3:20]

Participants

7

Reactant 4

HCID 9773Ethanamine, 2,2,2-trifluoro-HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 24765575N-[(1R)-1-(5-bromopyridin-2-yl)ethyl]-2-(4-isopropylphenyl)acetamide

Product 1

HCID 579484732-(4-isopropylphenyl)-N-((1R)-1-{5-[(2,2,2-trifluoroethyl)amino]pyridin-2-yl}ethyl)acetamide

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To a 10.0 ml microwave reaction tube was added N-[(1R)-1-(5-bromopyridin-2-yl)ethyl]-2-(4-isopropylphenyl)acetamide (0.100 g, 0.277 mmol), trifluoroethylamine (0.025 ml, 0.332 mmol), NaOtBu (0.042 g, 0.441 mmol), (+/−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.018 g, 0.029 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.013 g, 0.015 mmol) and 2.5 ml of anhydrous toluene. N2 was bubbled through the mixture while stirring for 5 minutes. Then it was heated at 120° C. for 15 minutes in a microwave reaction chamber. Cooled to room temperature, filtered and concentrated. The residue was purified using reverse phase HPLC to afford 2-(4-isopropylphenyl)-N-((1R)-1-{5-[(2,2,2-trifluoroethyl)amino]pyridin-2-yl}ethyl)acetamide as a white solid. 1H NMR (CDCl3, 400 MHz) δ 8.291 (d, J=6.84 Hz, 1H); 8.174 (s, 1H); 7.516 (d, J=8.79 Hz, 1H); 7.357 (d, J=8.79 Hz, 1H); 7.167 (d, J=8.30 Hz, 2H); 7.141 (d, J=8.30 Hz, 2H); 5.823 (br s, 1H); 5.106 (dq, J=7.32 Hz, 1H); 3.692 (br d, J=7.57 Hz, 2H); 3.543 (d, J=14.90 Hz, 1H); 3.501 (d, J=15.14 Hz, 1H); 2.852 (sept, J=6.83 Hz, 1H); 1.563 (d, J=7.08 Hz, 3H); 1.199 (d, J=7.08 Hz, 6H); MS (Electrospray): m/z 380.1 (M+H).

Workup

  1. customN2 was bubbled through the mixture
  2. temperatureCooled to room temperature
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified

Sources & evidence

ORD record
ord-4b6e9e5c8c0848a6a12fff038fab9d6c
Source dataset
uspto-grants-2012_09
Patent number
US08263627B2

Reaction notes

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