Sodium Thiosulfate → 7-{[4-(Cyclopropylcarbonyl)-1H-pyrazol-1-yl]methyl}-4-(4-fluorophenyl)quinoline-2-carboxamide

HRID 922766Notes

Reaction equation

HRID 922766 reaction equation
[CH:1]1([CH:4]([OH:31])[C:5]2[CH:6]=[N:7][N:8]([CH2:10][C:11]3[CH:20]=[C:19]4[C:14]([C:15]([C:24]5[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=5)=[CH:16][C:17]([C:21]([NH2:23])=[O:22])=[N:18]4)=[CH:13][CH:12]=3)[CH:9]=2)[CH2:3][CH2:2]1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[O-]S([O-])(=S)=O.[Na+].[Na+].C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH:1]1([C:4]([C:5]2[CH:6]=[N:7][N:8]([CH2:10][C:11]3[CH:20]=[C:19]4[C:14]([C:15]([C:24]5[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=5)=[CH:16][C:17]([C:21]([NH2:23])=[O:22])=[N:18]4)=[CH:13][CH:12]=3)[CH:9]=2)=[O:31])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 24477Sodium ThiosulfateHCID 159087TriacetoxyperiodinaneHCID 516892Sodium BicarbonateHCID 715657377-({4-[Cyclopropyl(hydroxy)methyl]-1H-pyrazol-1-yl}methyl)-4-(4-fluorophenyl)quinoline-2-carboxamide

Product 1

HCID 715657387-{[4-(Cyclopropylcarbonyl)-1H-pyrazol-1-yl]methyl}-4-(4-fluorophenyl)quinoline-2-carboxamideYield 15.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a room temperature solution of 7-({4-[cyclopropyl(hydroxy)methyl]-1H-pyrazol-1-yl}methyl)-4-(4-fluorophenyl)quinoline-2-carboxamide (3-10, 22 mg, 0.053 mmol, 1.0 equiv.) in methylene chloride (1.0 mL) was added Dess-Martin Periodinane (67.2 mg, 0.158 mmol, 3.0 equiv.) and the mixture was stirred at room temperature overnight. Aqueous Na2S2O3 (saturate, 2.0 mL) and aqueous sodium hydrogen carbonate (saturate, 5.0 mL) were added and the mixture was extracted with ethyl acetate (3×5 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier) to afford 7-{[4-(cyclopropylcarbonyl)-1H-pyrazol-1-yl]methyl}-4-(4-fluorophenyl)quinoline-2-carboxamide (3-11, 3.30 mg, 15.1%) as a colorless solid. 1H NMR (400 MHz, CDCl3): δ 8.239 (s, 1H); 8.179 (br s, 1H); 8.088 (s, 1H); 8.039 (s, 1H); 8.017 (s, 1H); 7.965 (d, J=8.81 Hz, 1H); 7.466-7.510 (m, 3H); 7.219-7.263 (m, 2H); 6.369 (br s, 1H); 5.585 (s, 2H); 2.283-2.345 (m, 1H); 1.187-1.225 (m, 2H); 0.958-1.004 (m, 2H). LRMS m/z (M+H)+ 415.2 found, 415.2 required.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×5 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier)

Sources & evidence

ORD record
ord-0f552d5507844e89b63d8bd7d4899629
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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