Toluene → 5-fluoro-3-methyl-N-(2-(methylsulfonyl)-5-morpholinophenyl)-2-(pyridin-2-yl)quinolin-4-amine

HRID 1431605Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[F:12])[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[C:3]=1[CH3:19].[CH3:20][S:21]([C:24]1[CH:30]=[CH:29][C:28]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)=[CH:27][C:25]=1[NH2:26])(=[O:23])=[O:22].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]=[CH:8][CH:7]=[C:6]2[C:11]=1[C:2]([NH:26][C:25]1[CH:27]=[C:28]([N:31]3[CH2:32][CH2:33][O:34][CH2:35][CH2:36]3)[CH:29]=[CH:30][C:24]=1[S:21]([CH3:20])(=[O:23])=[O:22])=[C:3]([CH3:19])[C:4]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1)=[N:5]2

Participants

Conditions

Temperature: 90 °C

Procedure

A screw-cap vial was charged with 4-chloro-5-fluoro-3-methyl-2-(pyridin-2-yl)-quinoline (50 mg, 0.18 mmol), 2-(methylsulfonyl)-5-morpholinoaniline (47.0 mg, 0.18 mmol), XPhos precatalyst (CAS 1028206-56-5; 27.1 mg, 0.037 mmol), sodium tert-butoxide (44.1 mg, 0.46 mmol), and toluene (1.8 mL). The mixture was stirred at 90° C. for 2 h, then cond. The crude residue was dissolved in EtOAc, washed with water, and the organic layer was dried over magnesium sulfate and cond. The crude product was purified by reverse-phase HPLC (0-70% acetonitrile in water), affording 5-fluoro-3-methyl-N-(2-(methylsulfonyl)-5-morpholinophenyl)-2-(pyridin-2-yl)quinolin-4-amine as an amorphous beige solid. Mass Spectrum (ESI) m/e=493.0 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 8.80 (1H, br. s), 8.72 (1H, d, J=4.7 Hz), 8.14 (1H, br. s), 7.95 (2H, br. s.), 7.80 (1H, d, J=9.0 Hz), 7.64 (1H, m), 7.42 (1H, d, J=3.3 Hz), 7.20 (1H, m), 6.52 (1H, d, J=9.2 Hz), 6.04 (1H, s), 3.70-3.81 (4H, m), 3.18 (3H, s), 3.05-3.17 (4H, m), 2.30 (3H, s).

Workup

washwashed with water
dry with materialthe organic layer was dried over magnesium sulfate and cond
customThe crude product was purified by reverse-phase HPLC (0-70% acetonitrile in water)

Sources & evidence

ORD record: ord-e0a4aff6f51e43d6929f089c7a90a512
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940724B2

Reaction notes

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