Potassium Carbonate → HCID 117737079, compound

HRID 1504511Notes

Reaction equation

HRID 1504511 reaction equation
Br[C:2]1[C:3]([Cl:30])=[CH:4][C:5]([O:28][CH3:29])=[C:6]([N:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([NH:21][C:22]4[CH:26]=[CH:25][O:24][N:23]=4)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[CH:11]=[CH:10][C:9]2=[O:27])[CH:7]=1.[Cl:31][C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[C:36]([F:38])[CH:37]=1.C(=O)([O-])[O-].[K+].[K+].[Cl-].[NH4+]>O1CCOCC1.O.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:31][C:32]1[CH:33]=[C:34]([C:2]2[C:3]([Cl:30])=[CH:4][C:5]([O:28][CH3:29])=[C:6]([N:8]3[C:17]4[C:12](=[CH:13][C:14]([S:18]([NH:21][C:22]5[CH:26]=[CH:25][O:24][N:23]=5)(=[O:20])=[O:19])=[CH:15][CH:16]=4)[CH:11]=[CH:10][C:9]3=[O:27])[CH:7]=2)[CH:35]=[C:36]([F:38])[CH:37]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 15391287(3-Chloro-5-fluorophenyl)boronic acidHCID 117737014HCID 117737014, compound

Product 1

HCID 117737079HCID 117737079, compoundYield 64.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

1-(5-Bromo-4-chloro-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.484 g, 0.948 mmol), (3-chloro-5-fluorophenyl)boronic acid (0.248 g, 1.421 mmol), potassium carbonate (0.393 g, 2.84 mmol), and Pd(PPh3)4 (0.110 g, 0.095 mmol) were combined in 1,4-dioxane (3.55 ml) and water (1.185 ml). The reaction was heated to 90° C. for 2 h. The reaction was cooled to RT and sat. aq. ammonium chloride was added. The organics were extracted (×3) with DCM, dried via phase separator, and concentrated in vacuo. The crude material was purified via MPLC, eluting with 0-100% ethyl acetate in heptanes, to yield 1-(3′,6-dichloro-5′-fluoro-4-methoxy-[1,1′-biphenyl]-3-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.344 g, 0.614 mmol, 64.8% yield). m/z (ESI) 562.0 (M+H)+. 1 H NMR (400 MHz, DMSO-d6) δ ppm 3.76 (s, 3 H) 6.45 (d, J=1.76 Hz, 1 H) 6.79 (d, J=9.64 Hz, 1 H) 6.93 (d, J=9.02 Hz, 1 H) 7.35 (ddd, J=9.59, 2.38, 1.50 Hz, 1 H) 7.39-7.41 (m, 1 H) 7.49 (dt, J=8.73, 2.11 Hz, 1 H) 7.57 (d, J=5.08 Hz, 2H) 7.84 (dd, J=9.02, 2.28 Hz, 1 H) 8.22 (d, J=9.54 Hz, 1 H) 8.37 (d, J=2.18 Hz, 1 H) 8.72 (d, J=1.76 Hz, 1 H) 11.66 (s, 1 H). The material was separated by chiral SFC on a Chiralpak AD with 45% isopropanol to give (P)-1-(3′,6-dichloro-5′-fluoro-4-methoxy-3-biphenylyl)-N-3-isoxazolyl-2-oxo-1,2-dihydro-6-quinolinesulfonamide as peak 1 and (M)-1-(3′,6-dichloro-5′-fluoro-4-methoxy-3-biphenylyl)-N-3-isoxazolyl-2-oxo-1,2-dihydro-6-quinolinesulfonamide as peak 2. Data for peak 1: m/z (ESI) 560.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.76 (s, 3 H) 6.45 (d, J=1.76 Hz, 1 H) 6.79 (d, J=9.64 Hz, 1 H) 6.93 (d, J=8.91 Hz, 1 H) 7.35 (d, J=9.51 Hz, 1 H) 7.40 (s, 1 H) 7.49 (dt, J=8.76, 2.15 Hz, 1 H) 7.57 (d, J=5.18 Hz, 2 H) 7.84 (dd, J=9.02, 2.28 Hz, 1 H) 8.22 (d, J=9.43 Hz, 1 H) 8.37 (d, J=2.28 Hz, 1 H) 8.72 (d, J=1.76 Hz, 1 H) 11.66 (s, 1 H). Data for peak 2: m/z (ESI) 560.0 (M+H)+. 1 H NMR (400 MHz, DMSO-d6) δ ppm 3.76 (s, 3 H) 6.45 (d, J=1.76 Hz, 1 H) 6.79 (d, J=9.64 Hz, 1 H) 6.93 (d, J=8.91 Hz, 1 H) 7.35 (ddd, J=9.61, 2.36, 1.50 Hz, 1 H) 7.39-7.41 (m, 1 H) 7.49 (dt, J=8.71 Hz, 1 H) 7.57 (d, J=5.18 Hz, 2 H) 7.84 (dd, J=8.97, 2.23 Hz, 1 H) 8.22 (d, J=9.54 Hz, 1 H) 8.37 (d, J=2.18 Hz, 1 H) 8.72 (d, J=1.76 Hz, 1 H) 11.66 (s, 1 H).

Workup

  1. temperatureThe reaction was cooled to RT
  2. extractionThe organics were extracted (×3) with DCM
  3. customdried via phase separator
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified via MPLC
  6. washeluting with 0-100% ethyl acetate in heptanes

Sources & evidence

ORD record
ord-d7f5ba3e95d143be9d2edb2aee6e32c6
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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