Trifluoroacetic acid → HCID 25118300, compound

HRID 557755Notes

Reaction equation

HRID 557755 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]([C:23]3[N:24]=[C:25]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[O:38][C:39]([F:42])([F:41])[F:40])[O:26][C:27]=3[C:28]([F:31])([F:30])[F:29])=[O:22])=[CH:16][N:15]=2)[CH2:9]1)=[O:7])(C)(C)[CH3:2].FC(F)(F)C(O)=O.ClC(OCC)=O.C(N(CC)CC)C>>[CH2:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]([C:23]3[N:24]=[C:25]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[O:38][C:39]([F:42])([F:41])[F:40])[O:26][C:27]=3[C:28]([F:29])([F:30])[F:31])=[O:22])=[CH:16][N:15]=2)[CH2:9]1)=[O:7])[CH3:2]

Participants

5

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 86629271HCID 86629271, compound

Product 1

HCID 25118300HCID 25118300, compoundYield 42.7%

Conditions

Temperature
0 °C

Procedure

To a flask containing (S)-3-(5-{[2-(2-trifluoromethoxy-phenyl)-5-trifluoromethyl-oxazole-4-carbonyl]-amino}-pyridin-2-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester (150 mg, 0.249 mmol) was added trifluoroacetic acid (5 mL). When all the starting material was consumed, as indicated by TLC, the reaction mixture was concentrated to dryness. The residue was dissolved in dichloromethane (10 mL) and then cooled to 0° C. Ethyl chloroformate (24 μL, 0.249 mmol) and triethylamine (75.5 mg, 0.747 mmol) were added dropwise, and the reaction mixture was stirred for 2 h at room temperature and then concentrated. The crude product was purified by flash chromatography (Merck silica gel 60, 230-400 mesh, gradient elution with 0%-100% ethyl acetate in hexane) to give (S)-3-(5-{[2-(2-trifluoromethoxy-phenyl)-5-trifluoromethyl-oxazole-4-carbonyl]-amino}-pyridin-2-ylamino)-pyrrolidine-1-carboxylic acid ethyl ester (61 mg, 42.7% yield) as a light yellow solid. LCMS for C24H21F6N5O5 calculated (m/e) 573.46, found 574.15 (M+H).

Workup

  1. customWhen all the starting material was consumed
  2. concentrationthe reaction mixture was concentrated to dryness
  3. dissolutionThe residue was dissolved in dichloromethane (10 mL)
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography (Merck silica gel 60, 230-400 mesh, gradient elution with 0%-100% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-eb64c890f3604a578c7cb3d10c69783c
Source dataset
uspto-grants-2011_11
Patent number
US08058299B2

Reaction notes

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