HCID 117737112, compound → HCID 117737025, compound

HRID 1504409Notes

Reaction equation

HRID 1504409 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][CH3:30])[CH:3]=1.[Br-].[CH2:32]([Zn+])[C:33]([CH3:36])([CH3:35])[CH3:34]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.C1COCC1>[F:8][C:7]1[C:2]([CH2:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[CH:3][C:4]([O:29][CH3:30])=[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])[CH:6]=1

Participants

5

Reactant 2

HCID 117737112HCID 117737112, compoundHCID 178445880HCID 178445880, compound

Product 1

HCID 117737025HCID 117737025, compoundYield 24.43%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

A vial was charged with 1-(4-bromo-5-fluoro-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.100 g, 0.202 mmol) and PdCl2(dppf)-CH2Cl2 (0.017 g, 0.020 mmol). The vial was flushed with Ar (g), then THF (1.012 ml) and neopentylzinc bromide, 0.5 M in THF (1.5 ml, 0.750 mmol) were added. The reaction was heated to 70° C. and stirred for one hour. The reaction was purified via column chromatography (RediSep Gold 40 g, gradient elution 10-75% [3:1 EtOAc/EtOH]:Heptane) to afford 1-(5-fluoro-2-methoxy-4-neopentylphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.024 g, 0.049 mmol, 24.43% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ=11.66 (s, 1 H), 8.72 (d, J=1.8 Hz, 1 H), 8.35 (d, J=2.2 Hz, 1 H), 8.21 (d, J=9.6 Hz, 1 H), 7.85 (dd, J=2.2, 9.0 Hz, 1 H), 7.29 (d, J=9.5 Hz, 1 H), 7.10 (d, J=6.6 Hz, 1 H), 6.77 (t, J=9.8 Hz, 2 H), 6.44 (d, J=1.8 Hz, 1 H), 3.64 (s, 3 H), 2.62 (s, 2 H), 0.99 (s, 9 H). m/z (ESI) 486.2 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. customThe reaction was purified via column chromatography (RediSep Gold 40 g, gradient elution 10-75% [3:1 EtOAc/EtOH]:Heptane)

Sources & evidence

ORD record
ord-eafd2a1a511a4ff985268d83956e5ef1
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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