Trifluoroacetic acid → (3S)-3-amino-4-cyclobutyl-N-cyclopropyl-2-hydroxy-butanamide trifluoroacetic acid salt

HRID 1511459Notes

Reaction equation

HRID 1511459 reaction equation
C(OC(=O)[NH:7][C@H:8]([CH:14]([OH:21])[C:15]([NH:17][CH:18]1[CH2:20][CH2:19]1)=[O:16])[CH2:9][CH:10]1[CH2:13][CH2:12][CH2:11]1)(C)(C)C.[F:23][C:24]([F:29])([F:28])[C:25]([OH:27])=[O:26]>ClCCl>[F:23][C:24]([F:29])([F:28])[C:25]([OH:27])=[O:26].[NH2:7][C@@H:8]([CH2:9][CH:10]1[CH2:11][CH2:12][CH2:13]1)[CH:14]([OH:21])[C:15]([NH:17][CH:18]1[CH2:20][CH2:19]1)=[O:16]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57893118HCID 57893118, compound

Product 1

HCID 68739749(3S)-3-amino-4-cyclobutyl-N-cyclopropyl-2-hydroxy-butanamide trifluoroacetic acid salt

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Tert-butyl-(2S)-1-cyclobutyl-4-(cyclopropylamino)-3-hydroxy-4-oxobutan-2-ylcarbamate (51 mg, 0.165 mmol) was dissolved in dichloromethane (3.0 mL) and trifluoroacetic acid (3.0 mL) was added. After stirring for 1 hour at room temperature, the reaction mixture was evaporated to dryness to give (3S)-3-amino-4-cyclobutyl-N-cyclopropyl-2-hydroxy-butanamide trifluoroacetic acid salt as a white solid. A solution of (2S,4R)-1-((S)-2-(3-tert-butylureido)-3,3-dimethylbutanoyl)-4-(7-methoxy-2-(1H-pyrazol-1-yl)quinolin-4-yloxy)pyrrolidine-2-carboxylic acid in dichloromethane/N,N-dimethylformamide (1:1, 6.0 mL) was added to the (3S)-3-amino-4-cyclobutyl-N-cyclopropyl-2-hydroxy-butanamide trifluoroacetic acid salt followed by O (7 azabenzotriazol 1 yl) 1,1,3,3 tetramethyl-uronium hexafluorophosphate (HATU) (75 mg, 0.198 mmol) and diisopropylethylamine (0.1 mL, 0.7 mmol). After 24 hours at room temperature, the reaction mixture was diluted with ethyl acetate and washed with 1N HCl, saturated sodium bicarbonate, and brine. The ethyl acetate layer was dried (magnesium sulfate), filtered and evaporated to dryness under reduced pressure. The crude product was then dissolved in dry dichloromethane (10.0 mL) and 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (Dess-Martin periodinane reagent, 112 mg, 0.264 mmol) added. After stirring at room temperature for 2 hours, the reaction mixture was quenched with 0.26M sodium thiosulfate in saturated sodium bicarbonate and extracted with ethyl acetate. The combined ethyl acetate layers were then washed with saturated sodium bicarbonate and brine. Purification by preparative HPLC gave (2S,4R)-1-((S)-(3-tert-butylureido)-3,3-dimethylbutanoyl]-N-((S)-1-cyclobutyl-4-(cyclopropylamino)-3,4-dioxobutan-2-yl)-4-(7-methoxy-2-(1H-pyrazol-1-yl)-quinolin-4-yloxy)pyrrolidine-2-carboxamide in >99% purity by HPLC.

Workup

  1. customthe reaction mixture was evaporated to dryness

Sources & evidence

ORD record
ord-94ff184b7d7b4318930f3c2bb65f0837
Source dataset
uspto-grants-2012_07
Patent number
US08211897B2

Reaction notes

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