Potassium Carbonate → HCID 117737148, compound

HRID 1504457Notes

Reaction equation

HRID 1504457 reaction equation
Br[C:2]1[C:7]([Cl:8])=[CH:6][C:5]([N:9]2[C:18]3[C:13](=[CH:14][C:15]([S:19]([NH:22][C:23]4[CH:27]=[CH:26][O:25][N:24]=4)(=[O:21])=[O:20])=[CH:16][CH:17]=3)[CH:12]=[CH:11][C:10]2=[O:28])=[C:4]([O:29][CH3:30])[CH:3]=1.[Cl:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][C:33]=1[CH3:41].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:8][C:7]1[CH:6]=[C:5]([N:9]2[C:18]3[C:13](=[CH:14][C:15]([S:19]([NH:22][C:23]4[CH:27]=[CH:26][O:25][N:24]=4)(=[O:20])=[O:21])=[CH:16][CH:17]=3)[CH:12]=[CH:11][C:10]2=[O:28])[C:4]([O:29][CH3:30])=[CH:3][C:2]=1[C:35]1[CH:36]=[CH:37][C:32]([Cl:31])=[C:33]([CH3:41])[CH:34]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 3786632(4-Chloro-3-methylphenyl)boronic acidHCID 117736950HCID 117736950, compound

Product 1

HCID 117737148HCID 117737148, compound

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

The following compounds were made via method 65. A vial was charged with 1-(4-bromo-5-chloro-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.300 g, 0.587 mmol), (4-chloro-3-methylphenyl)boronic acid (0.150 g, 0.881 mmol), potassium carbonate (0.244 g, 1.762 mmol), and Pd(Ph3P)4 (0.068 g, 0.059 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (2.2 mL) and water (0.73 mL) were added. The vial was sealed and heated to 90° C. for 2 h. The mixture was cooled, quenched with NH4Cl and extracted with EtOAc (5×). The combined organic extracts were concentrated, dried over magnesium sulfate and concentrated. The residue was purified by chromatography on silica gel (40-g Ultra SNAP column, 25-g silica gel loading column, 0-50% EtOAc/Heptane) to give 1-(2,4′-dichloro-5-methoxy-3′-methyl-[1,1′-biphenyl]-4-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide. This material was purified by chiral SFC on Chiralpak AS-H column (25% MeOH/75% CO2) to give (P)-1-(2,4′-dichloro-5-methoxy-3′-methyl-[1,1′-biphenyl]-4-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide as peak 1 and (M)-1-(2,4′-dichloro-5-methoxy-3′-methyl-[1,1′-biphenyl]-4-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide as peak 2, both as off-white solids. Data for peak 1: 1H NMR (400 MHz, DMSO-d6) δ=11.68 (br. s., 1H), 8.66 (s, 1H), 8.35 (d, J=1.96 Hz, 1H), 8.23 (d, J=9.68 Hz, 1H), 7.86 (dd, J=2.10, 8.95 Hz, 1H), 7.67 (s, 1H), 7.55-7.61 (m, 2H), 7.44 (dd, J=1.71, 8.27 Hz, 1H), 7.32 (s, 1H), 6.77-6.88 (m, 2H), 6.41 (d, J=1.66 Hz, 1H), 3.73 (s, 3H), 2.44 (s, 3H). m/z (ESI) 557.1 (M+H)+. Data for peak 2: 1H NMR (400 MHz, DMSO-d6) δ=11.68 (br. s., 1H), 8.63 (br. s., 1H), 8.33 (d, J=1.86 Hz, 1H), 8.22 (d, J=9.68 Hz, 1H), 7.82-7.88 (m, 1H), 7.67 (s, 1H), 7.57-7.60 (m, 2H), 7.41-7.47 (m, 1H), 7.32 (s, 1H), 6.77-6.85 (m, 2H), 6.39 (s, 1H), 3.72 (s, 3H), 2.44 (s, 3H). m/z (ESI) 557.1 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (2.2 mL) and water (0.73 mL) were added
  3. customThe vial was sealed
  4. temperatureThe mixture was cooled
  5. customquenched with NH4Cl
  6. extractionextracted with EtOAc (5×)
  7. concentrationThe combined organic extracts were concentrated
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. customThe residue was purified by chromatography on silica gel (40-g Ultra SNAP column, 25-g silica gel loading column, 0-50% EtOAc/Heptane)

Sources & evidence

ORD record
ord-94f24aea8cad4397a4f2f2efa023a662
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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