Methanesulfinic acid → N-(2,5-dimorpholinopyridin-3-yl)-7-fluoro-3-methyl-2-(2-(methylsulfonyl)-5-nitrophenyl)quinolin-4-amine

HRID 1431634Notes

Reaction equation

HRID 1431634 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:12]([NH:13][C:14]3[C:23]4[C:18](=[CH:19][C:20]([F:24])=[CH:21][CH:22]=4)[N:17]=[C:16]([C:25]4[CH:30]=[C:29]([N+:31]([O-:33])=[O:32])[CH:28]=[CH:27][C:26]=4F)[C:15]=3[CH3:35])=[CH:11][C:10]([N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)=[CH:9][N:8]=2)[CH2:3][CH2:2]1.[CH3:42][S:43]([OH:45])=[O:44].[Na]>CC(N(C)C)=O>[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:12]([NH:13][C:14]3[C:23]4[C:18](=[CH:19][C:20]([F:24])=[CH:21][CH:22]=4)[N:17]=[C:16]([C:25]4[CH:30]=[C:29]([N+:31]([O-:33])=[O:32])[CH:28]=[CH:27][C:26]=4[S:43]([CH3:42])(=[O:45])=[O:44])[C:15]=3[CH3:35])=[CH:11][C:10]([N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)=[CH:9][N:8]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 87251Methanesulfinic acidHCID 5360545SodiumHCID 59631298N-(2,5-dimorpholinopyridin-3-yl)-7-fluoro-2-(2-fluoro-5-nitrophenyl)-3-methylquinolin-4-amine

Product 1

HCID 59631575N-(2,5-dimorpholinopyridin-3-yl)-7-fluoro-3-methyl-2-(2-(methylsulfonyl)-5-nitrophenyl)quinolin-4-amine

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

The N-(2,5-dimorpholinopyridin-3-yl)-7-fluoro-2-(2-fluoro-5-nitrophenyl)-3-methylquinolin-4-amine (66 mg, 0.112 mmol) and methanesulfinic acid, sodium salt (12.0 mg, 0.112 mmol) was added to dimethylacetamide (0.24 mL) and placed in a microwave reactor for 2 h at 150° C. An LCMS was taken and ˜35% of starting material had converted to desired product. The mixture was reheated and stirred at 150° C. for 4 h. The reaction was then diluted with water (20 mL) and extracted with EtOAc (2×30 mL). The combined organic layers were washed with water (1×30 mL) and brine (1×30 mL) and dried over magnesium sulfate. The mixture was purified by reverse-phase preparative HPLC using a Phenomenex Gemini™ column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 90% over 20 minutes to provide N-(2,5-dimorpholinopyridin-3-yl)-7-fluoro-3-methyl-2-(2-(methylsulfonyl)-5-nitrophenyl)-quinolin-4-amine after extraction with satd sodium bicarbonate. 1H NMR (CDCl3) δ ppm 8.48-8.56 (1H, m), 8.40-8.47 (1H, m), 8.31 (1H, s), 7.88-8.04 (1H, m), 7.67 (1H, dd, J=9.5, 2.6 Hz), 7.62 (1H, d, J=2.0 Hz), 7.38-7.47 (1H, m), 7.01 (1H, br. s.), 6.38 (1H, br. s.), 3.89-4.06 (4H, m), 3.76 (4H, t, J=4.6 Hz), 3.37-3.56 (2H, m), 2.93-3.28 (9H, m), 2.03 (3H, s). Mass Spectrum (ESI) m/e=623.3.3 (M+1).

Sources & evidence

ORD record
ord-45c057e2a53145318c67419016d1fe53
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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