Dichloromethane → HCID 117737105, compound

HRID 1504513Notes

Reaction equation

HRID 1504513 reaction equation
Br[C:2]1[C:7]([F: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][CH2:30][C:31]#[N:32])[CH:3]=1.[Cl:33][C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][C:35]=1[CH3:43].C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl>CN(C=O)C.O.CS(C)=O>[Cl:33][C:34]1[CH:39]=[CH:38][C:37]([C:2]2[CH:3]=[C:4]([O:29][CH2:30][C:31]#[N:32])[C:5]([N:9]3[C:18]4[C:13](=[CH:14][C:15]([S:19]([NH:22][C:23]5[CH:27]=[CH:26][O:25][N:24]=5)(=[O:21])=[O:20])=[CH:16][CH:17]=4)[CH:12]=[CH:11][C:10]3=[O:28])=[CH:6][C:7]=2[F:8])=[CH:36][C:35]=1[CH3:43]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 3786632(4-Chloro-3-methylphenyl)boronic acidHCID 117737018HCID 117737018, compound

Product 1

HCID 117737105HCID 117737105, compoundYield 26%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 1-(4-bromo-2-(cyanomethoxy)-5-fluorophenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.020 g, 0.039 mmol) and (4-chloro-3-methylphenyl)boronic acid (9.84 mg, 0.058 mmol) in DMF (0.154 ml) and water (0.039 ml) was added potassium carbonate (0.016 g, 0.116 mmol) followed by PdCl2dppf, DCM adduct (1.409 mg, 1.926 μmol). The resulting mixture was heated to 50° C. and stirred for 3.5 hours. The solution was then cooled to RT, dissolved in 1.5 ml of DMSO and passed through a 0.20 Micron filter. An additional 0.5 ml was used to rinse the reaction vial and the solution was passed through the same filter. The resulting. DMSO solution was purified by reverse-phase HPLC (Waters XBridge Prep Shield RP18 10 μm OBD 19×100 mm) gradient, 30 to 95% MeCN in water (containing 0.1% trifluoroacetic acid as an additive), flow rate 40 mL/min to yield 1-(4′-chloro-5-(cyanomethoxy)-2-fluoro-3′-methyl-[1,1′-biphenyl]-4-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (5.7 mgs, 26% yield). 1H NMR (500 MHz, DMSO-d6) □=ppm 2.45 (s, 3 H) 5.17-5.27 (m, 2 H) 6.79-6.91 (m, 1 H) 7.00 (br. s., 1 H) 7.10 (br. s., 1 H) 7.20 (br. s., 1 H) 7.54 (d, J=8.04 Hz, 2 H) 7.58-7.66 (m, 2 H) 7.69 (br. s., 1H) 7.87 (d, J=8.89 Hz, 1 H) 8.25 (d, J=7.98 Hz, 1 H) 8.39 (s, 1 H) 8.72 (s, 1 H). m/z (ESI) 565.0 (M+H)+.

Workup

  1. temperatureThe solution was then cooled to RT
  2. filtrationfilter
  3. washto rinse the reaction vial and the solution
  4. customDMSO solution was purified by reverse-phase HPLC (Waters XBridge Prep Shield RP18 10 μm OBD 19×100 mm) gradient, 30 to 95% MeCN in water (
  5. additioncontaining 0.1% trifluoroacetic acid as an additive), flow rate 40 mL/min

Sources & evidence

ORD record
ord-0f522dbefc09441a9191aa0c5a550f72
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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