1,4-Dioxane → HCID 86687593, compound

HRID 1473535Notes

Reaction equation

HRID 1473535 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1B(O)O.Cl[C:17]1[C:26]2[C:21](=[C:22]([CH3:45])[C:23]([S:27]([N:30](CC3C=CC(OC)=CC=3)[C:31]3[S:32][CH:33]=[CH:34][N:35]=3)(=[O:29])=[O:28])=[CH:24][CH:25]=2)[N:20]=[CH:19][CH:18]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1NC)(C)(C)C.O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[C:17]1[C:26]2[C:21](=[C:22]([CH3:45])[C:23]([S:27]([NH:30][C:31]3[S:32][CH:33]=[CH:34][N:35]=3)(=[O:28])=[O:29])=[CH:24][CH:25]=2)[N:20]=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 24901776(2-Methoxy-4-(trifluoromethyl)phenyl)boronic acidHCID 86687591HCID 86687591, compound

Product 1

HCID 86687593HCID 86687593, compound

Reagents, catalysts & solvents 2

HCID 178482226HCID 178482226, compoundCatalystHCID 962WaterSolvent

Procedure

To a microwave vial charged with (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (52.6 mg, 0.239 mmol), 4-chloro-N-(4-methoxybenzyl)-8-methyl-N-(thiazol-2-yl)quinoline-7-sulfonamide (100 mg, 0.217 mmol), potassium phosphate tribasic (54.0 μl, 0.652 mmol) and 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(II) chloride (15.39 mg, 0.022 mmol) was added dioxane (872 μl) and water (291 μl). The mixture was irradiated at 100° C. for 30 min affording conversion to desired product according to LC-MS. The organic layer was decanted and the aqueous extracted with EtOAc. The combined organics were dried under reduced pressure. The crude material was dissolved in DCM (3.0 ml) and TFA (1.0 ml) was added. The brown solution was stirred at room temperature for 1 hr affording complete PMB cleavage according to LC-MS. The light brown solution was dried under reduced pressure and the crude material purified with a 25 g Interchim column ramping EtOAc in heptane (0-100%) affording product (elution at 100% polar eluent) 4-(2-methoxy-4-(trifluoromethyl)phenyl)-8-methyl-N-(thiazol-2-yl)quinoline-7-sulfonamide (84 mg, 0.175 mmol, 81% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ=12.81 (s, 1H), 9.08 (d, J=4.3 Hz, 1H), 8.03 (d, J=8.9 Hz, 1H), 7.62-7.45 (m, 4H), 7.43 (d, J=8.9 Hz, 1H), 7.26 (d, J=4.6 Hz, 1H), 6.81 (d, J=4.6 Hz, 1H), 3.13 (s, 3H). m/z (ESI) 480.0 (M+H)+.

Workup

  1. customThe mixture was irradiated at 100° C. for 30 min

Sources & evidence

ORD record
ord-0e166b9d0d324ce29db386daf5b64b64
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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