1,4-Dioxane → HCID 86687588, compound

HRID 1473530Notes

Reaction equation

HRID 1473530 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](=[CH:22][C:23]([S:29]([N:32](CC3C=CC(OC)=CC=3)[C:33]3[S:34][CH:35]=[CH:36][N:37]=3)(=[O:31])=[O:30])=[C:24]([O:27][CH3:28])[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>[CH3:28][O:27][C:24]1[CH:25]=[C:26]2[C:21](=[CH:22][C:23]=1[S:29]([NH:32][C:33]1[S:34][CH:35]=[CH:36][N:37]=1)(=[O:31])=[O:30])[N:20]=[CH:19][CH:18]=[C:17]2[C:4]1[CH:5]=[CH:6][C:7]([C:9]([F:12])([F:11])[F:10])=[CH:8][C:3]=1[O:2][CH3:1]

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 24901776(2-Methoxy-4-(trifluoromethyl)phenyl)boronic acidHCID 86687586HCID 86687586, compound

Product 1

HCID 86687588HCID 86687588, compound

Reagents, catalysts & solvents 2

HCID 178482226HCID 178482226, compoundCatalystHCID 962WaterSolvent

Procedure

To a microwave vial charged with (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (35.6 mg, 0.162 mmol), 4-chloro-6-methoxy-N-(4-methoxybenzyl)-N-(thiazol-2-yl)quinoline-7-sulfonamide (70 mg, 0.147 mmol), potassium phosphate tribasic (36.5 μl, 0.441 mmol) and 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(ii) chloride (10.41 mg, 0.015 mmol) was added Dioxane (590 μl) and Water (197 μl). The mixture was irradiated at 100° C. for 30 mins affording conversion to desired product according to LC-MS. The mixture was dried under reduced pressure. To the crude oil was added DCM (0.9 ml) and TFA (0.3 ml) was added at room temperature. After 1 hr of stirring LC-MS indicated complete PMB cleavage. The mixture was dried under reduced pressure and purified with a 25 g (15 μm spherical silica) column ramping EtOAc in heptane (0-100%, 10% DCM throughout) providing product, obtained as a film. The material was lyophilized from MeOH/H2O providing 6-methoxy-4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)quinoline-7-sulfonamide (53 mg, 0.107 mmol, 72.7% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.62 (s, 3H) 3.80 (s, 3H) 6.83 (s, 1H) 6.88 (d, J=4.60 Hz, 1H) 7.28 (d, J=4.60 Hz, 1H) 7.47-7.54 (m, 3H) 7.57 (d, J=7.63 Hz, 1H) 8.52 (s, 1H) 8.91 (d, J=4.40 Hz, 1H) 12.80 (br. s., 1H). m/z (ESI) 496.2 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-0ceb719cd5ee4c9c962b5cdb2289adaf
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…