Nitrogen → HCID 117737203, compound

HRID 1504365Notes

Reaction equation

HRID 1504365 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]([N:22]([C:32]4[CH:36]=[CH:35][O:34][N:33]=4)[CH2:23][C:24]4[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=4)(=[O:21])=[O:20])=[CH:16][CH:17]=3)[CH:12]=[CH:11][C:10]2=[O:37])=[C:4]([O:38][CH3:39])[CH:3]=1.[OH:40][C:41]1[CH:46]=[C:45]([CH3:47])[CH:44]=[CH:43][N:42]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN[C@@H]1CCCC[C@H]1NC.N#N>[Cu]I.O1CCOCC1>[F:8][C:7]1[C:2]([N:42]2[CH:43]=[CH:44][C:45]([CH3:47])=[CH:46][C:41]2=[O:40])=[CH:3][C:4]([O:38][CH3:39])=[C:5]([N:9]2[C:18]3[C:13](=[CH:14][C:15]([S:19]([N:22]([C:32]4[CH:36]=[CH:35][O:34][N:33]=4)[CH2:23][C:24]4[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=4)(=[O:20])=[O:21])=[CH:16][CH:17]=3)[CH:12]=[CH:11][C:10]2=[O:37])[CH:6]=1

Participants

8

Reactant 5

HCID 947NitrogenHCID 10796Cesium carbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 117737047HCID 117737047, compoundHCID 178428601HCID 178428601, compound

Product 1

HCID 117737203HCID 117737203, compoundYield 3.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A blue-green dioxane (2.2 mL) slurry of 1-(4-bromo-5-fluoro-2-methoxyphenyl)-N-(isoxazol-3-yl)-N-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.683 g, 1.11 mmol), 2-hydroxy-4-methylpyridine (1.21 g, 11.1 mmol), cesium carbonate (0.543 g, 1.67 mmol), copper(I) iodide (0.212 g, 1.11 mmol), and trans-N,N′-dimethyl-1,2-cyclohexanediamine (0.18 mL, 1.17 mmol) was sparged with N2 for 45 min in a 40-mL vial. The sealed flask was then heated to 110° C. After stirring for 2 h, the reaction was then quenched with H2O and extracted thrice with EtOAc. The organic extracts were combined, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Column chromatography (25 g Snap Ultra column, 0% to 80% [3:1 EtOAc/EtOH]/hept gradient with 10% DCM) followed by additional column chromatography (55 g Interchim C18 PuriFlash column, 0-100% MeCN/H2O with 0.1% NH4OH) afforded 1-(5-fluoro-2-methoxy-4-(4-methyl-2-oxopyridin-1(2H)-yl)phenyl)-N-(isoxazol-3-yl)-N-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (25 mg, 0.039 mmol, 3.5% yield). m/z (ESI) 643.2 (M+H)+.

Workup

  1. customthe reaction was then quenched with H2O
  2. extractionextracted thrice with EtOAc
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7db8dddd35e743a7b9b2ceef6cc1e153
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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