Ammonium Chloride → N-3-isoxazolyl-1-(2-methoxy-5-(2-pyridinyl)phenyl)-2-oxo-1,2-dihydro-6-quinolinesulfonamide

HRID 1504441Notes

Reaction equation

HRID 1504441 reaction equation
Br[C:2]1[CH:3]=[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.[Br-].[N:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[Zn+].[Cl-].[NH4+]>C1COCC1.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>[O:24]1[CH:25]=[CH:26][C:22]([NH:21][S:18]([C:14]2[CH:13]=[C:12]3[C:17](=[CH:16][CH:15]=2)[N:8]([C:6]2[CH:7]=[C:2]([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][N:31]=4)[CH:3]=[CH:4][C:5]=2[O:28][CH3:29])[C:9](=[O:27])[CH:10]=[CH:11]3)(=[O:20])=[O:19])=[N:23]1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 1177371161-(5-Bromo-2-methoxy phenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamideHCID 178418723HCID 178418723, compound

Product 1

HCID 117737006N-3-isoxazolyl-1-(2-methoxy-5-(2-pyridinyl)phenyl)-2-oxo-1,2-dihydro-6-quinolinesulfonamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a vial charged with 1-(5-bromo-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.100 g, 0.210 mmol) and Pd(Ph3P)4 (0.024 g, 0.021 mmol) in THF (1.050 ml) was added pyridin-2-ylzinc(II) bromide (0.5M in THF) (2.100 ml, 1.050 mmol). The reaction was sealed and heated to 60° C. for 6.5 h. After cooling to RT, ammonium chloride (sat. aq) was added and the product extracted (×3) with DCM. The organics were dried via phase separator and concentrated in vacuo. The crude material was purified via MPLC, eluting with 20-100% ethyl acetate in heptanes to yield desired product, contaminated with triphenylphosphine oxide. The material was triturated in diethyl ether and filtered to yield N-(isoxazol-3-yl)-1-(2-methoxy-5-(pyridin-2-yl)phenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.070 g, 0.148 mmol, 70.3% yield) as a light yellow solid. MS (ESL pos. ion) m/z: [M+1] 475.1. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.74 (s, 3 H) 6.44 (d, J=1.76 Hz, 1 H) 6.79-6.85 (m, 2 H) 7.31 (t, J=5.85 Hz, 1 H) 7.42 (d, J=8.81 Hz, 1H) 7.52-7.67 (m, 2 H) 7.97 (d, J=8.01 Hz, 1 H) 8.06 (d, J=2.28 Hz, 1 H) 8.23 (d, J=9.64 Hz, 1 H) 8.31-8.41 (m, 2 H) 8.59-8.64 (m, 1 H) 8.72 (d, J=1.87 Hz, 1 H) 11.59-11.69 (m, 1 H).

Workup

  1. customThe reaction was sealed
  2. temperatureAfter cooling to RT
  3. extractionthe product extracted (×3) with DCM
  4. customThe organics were dried via phase separator
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified via MPLC
  7. washeluting with 20-100% ethyl acetate in heptanes

Sources & evidence

ORD record
ord-a530bbc7cecc4d9ea835de30ecbce526
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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