Methanesulfinic acid → {4-Chloro-8-methyl-2-(methylsulfonyl)-3-[4-(1H-pyrazol-1-yl)benzyl]quinolin-6-yl}(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

HRID 926641Notes

Reaction equation

HRID 926641 reaction equation
[N:1]1([C:6]2[CH:40]=[CH:39][C:9]([CH2:10][C:11]3[C:12](Cl)=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17]([C:22]([C:30]3[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=3)([C:24]3[N:28]([CH3:29])[CH:27]=[N:26][CH:25]=3)[OH:23])=[CH:16][C:15]=4[CH3:37])=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.[CH3:41][S:42]([OH:44])=[O:43]>CN(C=O)C>[Cl:21][C:20]1[C:19]2[C:14](=[C:15]([CH3:37])[CH:16]=[C:17]([C:22]([C:30]3[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=3)([C:24]3[N:28]([CH3:29])[CH:27]=[N:26][CH:25]=3)[OH:23])[CH:18]=2)[N:13]=[C:12]([S:42]([CH3:41])(=[O:44])=[O:43])[C:11]=1[CH2:10][C:9]1[CH:39]=[CH:40][C:6]([N:1]2[CH:5]=[CH:4][CH:3]=[N:2]2)=[CH:7][CH:8]=1

Participants

4

Reactant 2

HCID 87251Methanesulfinic acid2×HCID 74221529(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloro-8-methylquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol2×

Product 1

HCID 118006264{4-Chloro-8-methyl-2-(methylsulfonyl)-3-[4-(1H-pyrazol-1-yl)benzyl]quinolin-6-yl}(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloro-8-methylquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol (100 mg, 0.17 mmol, Intermediate 67), methanesulfinic acid (16.3 mg, 0.20 mmol), and DMF (2 mL) were combined in a reaction tube then sealed and heated to 100° C. and allowed to react at that temperature overnight. Analysis after overnight reaction showed only partial conversion, so additional methanesulfinic acid (13.3 mg, 0.17 mmol) was added and the vessel was resealed and heated to 100° C. for an additional 24 hours. The reaction vessel was then cooled to room temperature and solvent was removed by reduced pressure distillation. The crude residue was taken up into EtOAc, then extracted twice with a saturated, aqueous NH4Cl solution. The organic phase was separated, dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified via reverse phase chromatography using acetonitrile with ammonium hydroxide in water as eluent to afford the title compound. MS (ESI): mass calcd. for C32H27Cl2N5O3S, 631.1. m/z found, 632.5 [M+H]+. 1H NMR (600 MHz, CDCl3) δ ppm 8.73-8.69 (m, 1H), 7.87 (dd, J=2.5, 0.6 Hz, 1H), 7.68 (d, J=1.8 Hz, 1H), 7.65 (dd, J=1.9, 1.0 Hz, 1H), 7.60-7.57 (m, 2H), 7.37 (s, 1H), 7.35-7.30 (m, 4H), 7.20-7.16 (m, 2H), 6.44 (dd, J=2.5, 1.8 Hz, 1H), 6.37 (s, 1H), 5.06 (s, 2H), 4.48 (s, 1H), 3.39 (s, 3H), 2.92 (s, 3H), 2.74 (s, 3H).

Workup

  1. customthen sealed
  2. customto react at that temperature overnight
  3. customAnalysis after overnight reaction
  4. additionwas added
  5. temperatureheated to 100° C. for an additional 24 hours
  6. temperatureThe reaction vessel was then cooled to room temperature
  7. customsolvent was removed by reduced pressure distillation
  8. extractionextracted twice with a saturated, aqueous NH4Cl solution
  9. customThe organic phase was separated
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe crude material was purified via reverse phase chromatography

Sources & evidence

ORD record
ord-0cf1bcb0a7194440ad01633a23505fd9
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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