Potassium Carbonate → HCID 117737292, compound

HRID 1504408Notes

Reaction equation

HRID 1504408 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:11]2[C:20]3[C:15](=[CH:16][C:17]([S:21]([NH:24][C:25]4[CH:29]=[CH:28][O:27][N:26]=4)(=[O:23])=[O:22])=[CH:18][CH:19]=3)[CH:14]=[CH:13][C:12]2=[O:30])[C:5]([O:9][CH3:10])=[N:6][C:7]=1Cl.Cl.[F:32][C:33]1([F:37])[CH2:36][NH:35][CH2:34]1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([N:11]2[C:20]3[C:15](=[CH:16][C:17]([S:21]([NH:24][C:25]4[CH:29]=[CH:28][O:27][N:26]=4)(=[O:23])=[O:22])=[CH:18][CH:19]=3)[CH:14]=[CH:13][C:12]2=[O:30])[C:5]([O:9][CH3:10])=[N:6][C:7]=1[N:35]1[CH2:36][C:33]([F:37])([F:32])[CH2:34]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 117736975HCID 117736975, compound

Product 1

HCID 117737292HCID 117737292, compoundYield 34.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

A vial was charged with 1-(5,6-dichloro-2-methoxypyridin-3-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.100 g, 0.214 mmol), 3,3-difluoroazetidine hydrochloride (0.055 ml, 0.428 mmol), and potassium carbonate (0.053 g, 0.384 mmol). DMSO (1.070 ml) was added and the reaction was stirred at 130° C. overnight. The reaction was filtered through a syringe filter. The resulting solution was purified via reverse phase HPLC (Xbridge 19×100 mm, 10 um, 40 ml/min, 25-85% 0.1% TFA in Acetonitrile) to afford 1-(5-chloro-6-(3,3-difluoroazetidin-1-yl)-2-methoxypyridin-3-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.038 g, 0.073 mmol, 33.9% yield) as a brown oily solid. 1H NMR (500 MHz, DMSO-d6) δ=11.65 (br. s., 1H), 8.73 (d, J=1.7 Hz, 1H), 8.35 (d, J=2.0 Hz, 1H), 8.20 (d, J=9.7 Hz, 1H), 7.92-7.80 (m, 2H), 6.97 (d, J=9.0 Hz, 1H), 6.78 (d, J=9.6 Hz, 1H), 6.44 (d, J=1.7 Hz, 1H), 4.68 (t, J=12.6 Hz, 4H), 3.75 (s, 3H). m/z (ESI) 524.0 (M+H)+.

Workup

  1. filtrationThe reaction was filtered through a syringe
  2. filtrationfilter
  3. customThe resulting solution was purified via reverse phase HPLC (Xbridge 19×100 mm, 10 um, 40 ml/min, 25-85% 0.1% TFA in Acetonitrile)

Sources & evidence

ORD record
ord-16cc63e50aee499895d0ae1326e585b6
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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