Toluene → 5,7-difluoro-3-methyl-N-(2-(methylsulfonyl)-5-morpholinophenyl)-2-(2-(methylsulfonyl)phenyl)quinolin-4-amine

HRID 1431604Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:13])=[CH:9][C:10]=2[F:12])[N:5]=[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[S:20]([CH3:23])(=[O:22])=[O:21])[C:3]=1[CH3:24].[CH3:25][S:26]([C:29]1[CH:35]=[CH:34][C:33]([N:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)=[CH:32][C:30]=1[NH2:31])(=[O:28])=[O:27].CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].CCOC(C)=O>[F:12][C:10]1[CH:9]=[C:8]([F:13])[CH:7]=[C:6]2[C:11]=1[C:2]([NH:31][C:30]1[CH:32]=[C:33]([N:36]3[CH2:37][CH2:38][O:39][CH2:40][CH2:41]3)[CH:34]=[CH:35][C:29]=1[S:26]([CH3:25])(=[O:28])=[O:27])=[C:3]([CH3:24])[C:4]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[S:20]([CH3:23])(=[O:22])=[O:21])=[N:5]2

Participants

Conditions

Temperature: 95 °C

Procedure

A screw-cap vial was charged with 4-chloro-5,7-difluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)quinoline (50 mg, 0.136 mmol), 2-(methylsulfonyl)-5-morpholinoaniline (Matrix Scientific; 34.8 mg, 0.14 mmol), XPhos precatalyst (CAS 1028206-56-5; 10.0 mg, 0.014 mmol), sodium tert-butoxide (32.7 mg, 0.34 mmol), and toluene (1.5 mL). The mixture was stirred at 95° C. under nitrogen gas for 18 h. The reaction was then cond, and the resulting residue was dissolved in EtOAc. This solution was washed with water, and the product extracted twice with EtOAc and once with DCM. The combined organic layer was then dried over magnesium sulfate and cond, affording a crude residue that was purified by flash-chromatography (silica gel, 0-50% EtOAc in hexanes). This afforded 5,7-difluoro-3-methyl-N-(2-(methylsulfonyl)-5-morpholinophenyl)-2-(2-(methylsulfonyl)phenyl)quinolin-4-amine. Mass Spectrum (ESI) m/e=588.0 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 8.78 (1H, br. s.), 8.20 (1H, d, J=8.0 Hz), 7.66-7.86 (3H, m), 7.50 (1H, br. s.), 7.45 (1H, d, J=7.4 Hz), 7.08 (1H, br. s.), 6.43 (1H, d, J=8.8 Hz), 6.04 (1H, br. s.), 3.72 (4H, t, J=4.6 Hz), 3.17-3.23 (4H, m), 3.16 (3H, s), 3.13 (3H, s), 1.94 (3H, s).

Workup

washThis solution was washed with water
extractionthe product extracted twice with EtOAc and once with DCM
dry with materialThe combined organic layer was then dried over magnesium sulfate and cond

Sources & evidence

ORD record: ord-da7196ec7ca1438185a9a87bc91af592
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940724B2

Reaction notes

Loading…