Dimethylformamide → HCID 117737047, compound

HRID 1504364Notes

Reaction equation

HRID 1504364 reaction equation
[Br:1][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.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C.[CH3:42][O:43][C:44]1[CH:51]=[CH:50][C:47]([CH2:48]Cl)=[CH:46][CH:45]=1>O.C(Cl)Cl.CCOC(C)=O>[Br:1][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]([N:22]([C:23]4[CH:27]=[CH:26][O:25][N:24]=4)[CH2:48][C:47]4[CH:50]=[CH:51][C:44]([O:43][CH3:42])=[CH:45][CH:46]=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]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 699934-Methyloxybenzyl chlorideHCID 117737112HCID 117737112, compound

Product 1

HCID 117737047HCID 117737047, compoundYield 74.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 40-mL vial containing 1-(4-bromo-5-fluoro-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (750 mg, 1.517 mmol) and cesium carbonate (1483 mg, 4.55 mmol) was flushed with N2 and subsequently charged with DMF (2.5 mL) and 4-methoxybenzyl chloride (309 μl, 2.276 mmol). The brown slurry was stirred at rt for 5 d. The reaction was then diluted with H2O and extracted thrice with EtOAc. The organic extracts were combined, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to an oily orange residue. Column chromatography (25 g Snap Ultra column, 0% to 100% EtOAc/hept with 10% DCM) afforded 1-(4-bromo-5-fluoro-2-methoxyphenyl)-N-(isoxazol-3-yl)-N-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (697.8 mg, 1.136 mmol, 74.8% yield) as a yellow amorphous solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.71 (d, J=1.76 Hz, 6 H) 4.92 (s, 2 H) 6.74 (s, 1 H) 6.77-6.92 (m, 4 H) 7.22-7.29 (m, 2H) 7.59-7.72 (m, 2H) 7.76 (d, J=9.02 Hz, 1 H) 8.14-8.20 (m, 1 H) 8.38 (d, J=3.45 Hz, 1 H) 8.38 (s, 1 H) 8.82 (d, J=3.25 Hz, 1 H) 8.81 (s, 1 H). m/z (ESI) 614.0 (M+H)+.

Workup

  1. customwas flushed with N2
  2. extractionextracted thrice with EtOAc
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo to an oily orange residue

Sources & evidence

ORD record
ord-fbf04105be4f4d24a5c3407890dbf412
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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