Potassium Carbonate → HCID 118006176, compound

HRID 926627Notes

Reaction equation

HRID 926627 reaction equation
[Cl:1][C:2]1[C:11]([CH2:12][C:13]2[CH:18]=[CH:17][C:16](SC)=[CH:15][CH:14]=2)=[C:10]([Cl:21])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:22]([C:30]3[C:31]([CH3:37])=[N:32][C:33]([CH3:36])=[CH:34][CH:35]=3)([C:24]3[N:28]([CH3:29])[N:27]=[N:26][CH:25]=3)[OH:23])[CH:8]=2)[N:3]=1.ClC1C=CC=C(C(OO)=O)C=1.[CH3:49][S:50]([O-:53])(=O)=[O:51].CS(C1C=CC=C[N+]=1[O-])(=O)=O.BrP(Br)Br.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(Cl)Cl>[Cl:1][C:2]1[C:11]([CH2:12][C:13]2[CH:14]=[CH:15][C:16]([S:50]([CH3:49])(=[O:53])=[O:51])=[CH:17][CH:18]=2)=[C:10]([Cl:21])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:22]([C:30]3[C:31]([CH3:37])=[N:32][C:33]([CH3:36])=[CH:34][CH:35]=3)([C:24]3[N:28]([CH3:29])[N:27]=[N:26][CH:25]=3)[OH:23])[CH:8]=2)[N:3]=1

Participants

9

Reactant 6

HCID 11430Potassium CarbonateHCID 24614Phosphorus tribromide2×HCID 70297m-Chloroperbenzoic acidHCID 85257MethanesulfonateHCID 187085Pyridine, 2-(methylsulfonyl)-, 1-oxideHCID 118006319HCID 118006319, compound

Product 1

HCID 118006176HCID 118006176, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A suspension of (2,4-dichloro-3-(4-(methylthio)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol (1.10 g, 2.00 mmol, Example 95), 3-chloroperbenzoic acid (˜77%, 1.62 g, 7.23 mmol) and DCM (100 mL) was stirred at room temperature for 2.5 hours, during which it became a clear solution. LCMS showed mainly methylsulfonate product and methylsulfonyl pyridine-oxide by-product. To the mixture was added tribromophosphine (1.0 M in DCM, 3.2 mL, 3.2 mmol) dropwise (a white suspension formed at the end of the addition). DMF (10 mL) was then added and the suspension dissolved. After stirring for ˜30 minutes, additional tribromophosphine (1.0 M in DCM, 3.2 mL, 3.2 mmol) was added. After stirring for 1 hour, 1 M K2CO3 (aqueous) was added, the organic layer was separated. The aqueous layer was further extracted with DCM. The combined organic phases were washed with 1 M K2CO3 (aqueous), and the aqueous layer was back extracted with DCM. The organic phase was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, 30-100% EtOAc in heptanes, 10% MeOH in DCM) to provide the title compound. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.25 (d, J=2.02 Hz, 1H), 8.02 (d, J=9.09 Hz, 1H), 7.93 (br. s., 1H), 7.86 (d, J=8.59 Hz, 2H), 7.58 (dd, J=2.27, 8.84 Hz, 1H), 7.44 (d, J=8.59 Hz, 2H), 6.91-6.98 (m, 2H), 6.87 (s, 1H), 4.61 (s, 2H), 3.94 (s, 3H), 3.03 (s, 3H), 2.54 (s, 3H), 2.36 (s, 3H); MS m/e 582.2 [M+H]+.

Workup

  1. customformed at the end of the addition)
  2. dissolutionthe suspension dissolved
  3. stirringAfter stirring for ˜30 minutes
  4. stirringAfter stirring for 1 hour
  5. customthe organic layer was separated
  6. extractionThe aqueous layer was further extracted with DCM
  7. washThe combined organic phases were washed with 1 M K2CO3 (aqueous)
  8. extractionthe aqueous layer was back extracted with DCM
  9. dry with materialThe organic phase was dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by flash column chromatography (silica gel, 30-100% EtOAc in heptanes, 10% MeOH in DCM)

Sources & evidence

ORD record
ord-6270f6300b1c490cb332841c958b034e
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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