Diisopropylethylamine → (2S)-5,5,5-trifluoro-2-({(1S)-2,2,2-trifluoro-1-[4'-(methylsulfonyl)-1,1'-biphenyl-4-yl]ethyl}amino)pentanoic acid cyanomethyl amide

HRID 1620940Notes

Reaction equation

HRID 1620940 reaction equation
[F:1][C:2]([F:32])([F:31])[CH2:3][CH2:4][C@H:5]([NH:9][C@@H:10]([C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][CH:22]=2)=[CH:17][CH:16]=1)[C:11]([F:14])([F:13])[F:12])[C:6](O)=[O:7].Cl.[NH2:34][CH2:35][C:36]#[N:37].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.O.C(OCC)(=O)C>[C:36]([CH2:35][NH:34][C:6](=[O:7])[C@@H:5]([NH:9][C@@H:10]([C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:22]=[CH:23][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:25][CH:26]=2)=[CH:17][CH:16]=1)[C:11]([F:12])([F:14])[F:13])[CH2:4][CH2:3][C:2]([F:1])([F:32])[F:31])#[N:37]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11491918Aminoacetonitrile hydrochlorideHCID 86590547HCID 86590547, compound

Product 1

HCID 59715492(2S)-5,5,5-trifluoro-2-({(1S)-2,2,2-trifluoro-1-[4'-(methylsulfonyl)-1,1'-biphenyl-4-yl]ethyl}amino)pentanoic acid cyanomethyl amide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

(2S)-5,5,5-Trifluoro-2-({(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)pentanoic acid (0.55 g, 0.114 mmol), aminoacetonitrile hydrochloride (21 mg, 0.228 mmol) and HATU (43 mg, 0.114 mmol) were dissolved in DMF (2 mL) and the reaction mixture was cooled to −20° C. Diisopropylethylamine (0.10 mL, 0.57 mmol) was added and the reaction mixture was stirred at −20° C. for three hours and then at ambient temperature for 16 hours. Ethyl acetate (ca.30 mL) and water (ca.30 mL) were added and the mixture was shaken vigorously. The organic layer was washed with water, dried with magnesium sulfate, and filtered. The filtrate was concentrated by rotary evaporation and the residue was purified by silica gel chromatography using 30% ethyl acetate in hexanes as eluant to yield (2S)-5,5,5-trifluoro-2-({(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)pentanoic acid cyanomethyl amide as a white solid.

Workup

  1. waitat ambient temperature for 16 hours
  2. stirringthe mixture was shaken vigorously
  3. washThe organic layer was washed with water
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated by rotary evaporation
  7. customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-21165ef407fa4902b56a320527d0cef8
Source dataset
uspto-grants-2014_07
Patent number
US08772336B2

Reaction notes

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