Quinoline → US9321721, Example 7

HRID 631777Notes

Reaction equation

HRID 631777 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]#[C:23][C:24]([NH2:26])=[O:25])=[CH:18][CH:17]=1)=[O:14].N1C2C(=CC=CC=2)C=CC=1.[H][H]>[Pd].CC([O-])=O.CC([O-])=O.[Pb+2].CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:9])[F:10])=[CH:4][C:3]=1[NH:12][C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19](/[CH:22]=[CH:23]\[C:24]([NH2:26])=[O:25])=[CH:18][CH:17]=1)=[O:14]

Participants

6

Reactant 3

HCID 7047QuinolineHCID 903870243-{4-[({[2-Fluoro-5-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenyl}prop-2-ynamideHCID 178418361HCID 178418361, compound

Product 1

HCID 78427114US9321721, Example 7Yield 85%

Reagents, catalysts & solvents 2

HCID 131709914Lindlars catalystCatalyst2×HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-{4-[({[2-fluoro-5-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenyl}prop-2-ynamide (12.2 mg, 0.033 mmol), 0.005 mL quinoline, and 4 mg Lindlar catalyst in 1.5 mL EtOAc was reacted under a balloon of hydrogen. After 1.75 hours, an additional catalytic amount of Lindlar catalyst was added and the reaction continued for an additional 1 hour. The reaction mixture was partitioned between EtOAc and dilute aqueous HCl, the EtOAc layer washed with H2O, brine, dried with Na2SO4 and evaporated. The crude material was chromatographed eluting with hexane/acetone to give the title compound as a white solid (10.3 mg, 84%). 1H NMR (Acetone-d6) δ: 8.79 (d, J=7.9 Hz, 1H), 8.69 (br. s., 1H), 8.37 (br. s., 1H), 7.75 (d, J=8.5 Hz, 2H), 7.50 (d, J=8.8 Hz, 2H), 7.35-7.43 (m, 2H), 6.93 (br. s., 1H), 6.64 (d, J=12.9 Hz, 1H), 6.41 (br. s., 1H), 5.97 (d, J=12.9 Hz, 1H)

Workup

  1. waitthe reaction continued for an additional 1 hour
  2. customThe reaction mixture was partitioned between EtOAc and dilute aqueous HCl
  3. washthe EtOAc layer washed with H2O, brine
  4. dry with materialdried with Na2SO4
  5. customevaporated
  6. customThe crude material was chromatographed
  7. washeluting with hexane/acetone

Sources & evidence

ORD record
ord-1671af54c7614cfcb837b6a71ee9dfa0
Source dataset
uspto-grants-2016_04
Patent number
US09321721B2

Reaction notes

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