Potassium Carbonate → HCID 117736833, compound

HRID 1504407Notes

Reaction equation

HRID 1504407 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.[F:31][C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[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[C:36]1[CH:35]=[CH:34][CH:33]=[C:32]([F:31])[CH:37]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 117736975HCID 117736975, compound

Product 1

HCID 117736833HCID 117736833, compoundYield 41.7%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A microwave 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-fluorophenyl)boronic acid (0.045 g, 0.321 mmol), potassium carbonate (0.089 g, 0.642 mmol), and Pd(Ph3P)4 (0.025 g, 0.021 mmol). The vial was flushed with Ar (g), then dioxane (0.803 ml) and water (0.268 ml) were added. The reaction was microwaved at 90° C. for 30 minutes. The organic layer was pipetted off of the aqueous layer and concentrated. The resulting film was dissolved in DMSO and 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-fluorophenyl)-2-methoxypyridin-3-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.047 g, 0.089 mmol, 41.7% yield) as a tan solid. 1H NMR (500 MHz, DMSO-d6) δ=11.67 (br. s., 1 H), 8.73 (d, J=1.6 Hz, 1 H), 8.40 (d, J=1.9 Hz, 1 H), 8.30 (s, 1 H), 8.27 (d, J=9.7 Hz, 1 H), 7.87 (dd, J=2.1, 9.0 Hz, 1 H), 7.73 (d, J=7.7 Hz, 1 H), 7.67 (d, J=9.7 Hz, 1 H), 7.64-7.58 (m, 1 H), 7.42-7.33 (m, 1 H), 7.04 (d, J=9.0 Hz, 1 H), 6.84 (d, J=9.7 Hz, 1 H), 6.46 (d, J=1.6 Hz, 1H), 3.83 (s, 3H). m/z (ESI) 527.1 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. additiondioxane (0.803 ml) and water (0.268 ml) were added
  3. customThe reaction was microwaved at 90° C. for 30 minutes
  4. concentrationconcentrated
  5. dissolutionThe resulting film was dissolved in DMSO
  6. filtrationfiltered through a syringe
  7. filtrationfilter
  8. 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-2b07f861a9db45689d99806c645b2d1e
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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