HCID 86687543, compound → HCID 86687542, compound

HRID 1473488Notes

Reaction equation

HRID 1473488 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]=1[C:13]1[C:22]2[C:17](=[CH:18][C:19]([S:24]([N:27](CC3C=CC(OC)=CC=3)[C:28]3[S:29][CH:30]=[CH:31][N:32]=3)(=[O:26])=[O:25])=[CH:20][C:21]=2[CH3:23])[N:16]=[CH:15][CH:14]=1>CO.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:13]1[C:22]2[C:17](=[CH:18][C:19]([S:24]([NH:27][C:28]3[S:29][CH:30]=[CH:31][N:32]=3)(=[O:25])=[O:26])=[CH:20][C:21]=2[CH3:23])[N:16]=[CH:15][CH:14]=1

Participants

3

Reactant 1

HCID 86687543HCID 86687543, compound

Product 1

HCID 86687542HCID 86687542, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Procedure

To a microwave vial charged with (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (3.16 mg, 0.014 mmol), 4-chloro-N-(4-methoxybenzyl)-5-methyl-N-(thiazol-2-yl)quinoline-7-sulfonamide (6 mg, 0.013 mmol), potassium phosphate tribasic (3.24 μl, 0.039 mmol) and 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(ii) chloride (0.924 mg, 1.304 μmol) was added dioxane (52.3 μl) and water (17.44 μl). The mixture was irradiated at 100° C. for 30 min affording conversion to desired product according to LC-MS, 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-5-methyl-N-(thiazol-2-yl)quinoline-7-sulfonamide. m/z (ESI) 600.2 (M+H)+. 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 to 100%, 10% DCM throughout) providing product, obtained as a film. The material was lyophilized from MeOH/H2O providing 4-(2-methoxy-4-(trifluoromethyl)phenyl)-5-methyl-N-(thiazol-2-yl)quinoline-7-sulfonamide (2 mg, 4.17 μmol, 32.0% yield) as a yellow film. 1H NMR (500 MHz, DMSO-d6) δ ppm 3.75 (s, 3H) 6.86 (d, J=4.59 Hz, 1H) 7.28 (d, J=4.59 Hz, 1H) 7.38 (d, J=4.27 Hz, 1H) 7.41-7.48 (m, 2H) 7.49 (s, 1H) 7.63 (s, 1H) 8.32-8.39 (m, 1H) 8.99 (d, J=4.27 Hz, 1H). m/z (ESI) 480.2 (M+H)+.

Workup

  1. customThe mixture was dried under reduced pressure
  2. additionTo the crude oil was added DCM (0.9 ml) and TFA (0.3 ml)
  3. additionwas added at room temperature
  4. customThe mixture was dried under reduced pressure
  5. custompurified with a 25 g (15 μm spherical silica) column ramping EtOAc in heptane (0 to 100%, 10% DCM throughout)
  6. customproviding product
  7. customobtained as a film

Sources & evidence

ORD record
ord-a7776a77da984ef0bddd99e90cee2138
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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