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

HRID 1431603ノート

反応式

HRID 1431603 の反応式
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]=[C:18]([CH3:20])[CH:17]=[CH:16][N:15]=2)[C:3]=1[CH3:21].[CH3:22][S:23]([C:26]1[CH:32]=[CH:31][C:30]([N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)=[CH:29][C:27]=1[NH2:28])(=[O:25])=[O:24].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+].C(Cl)Cl>[F:12][C:10]1[CH:9]=[C:8]([F:13])[CH:7]=[C:6]2[C:11]=1[C:2]([NH:28][C:27]1[CH:29]=[C:30]([N:33]3[CH2:34][CH2:35][O:36][CH2:37][CH2:38]3)[CH:31]=[CH:32][C:26]=1[S:23]([CH3:22])(=[O:25])=[O:24])=[C:3]([CH3:21])[C:4]([C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][N:15]=1)=[N:5]2

参加物

7

反応物 4

HCID 1140TolueneHCID 23676156Sodium t-butoxideHCID 265977632-Methylsulfonyl-5-(morpholin-4-yl)anilineHCID 596311504-Chloro-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinoline

生成物 1

HCID 509071845,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)-N-(2-(methylsulfonyl)-5-morpholinophenyl)quinolin-4-amine

試薬・触媒・溶媒 2

HCID 54751079XPhos Palladacycle触媒HCID 6344Dichloromethane溶媒

反応条件

温度
95 °C

実験手順

A screw-cap vial was charged with 4-chloro-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinoline (50 mg, 0.16 mmol), 2-(methylsulfonyl)-5-morpholinoaniline (Matrix Scientific; 50.5 mg, 0.20 mmol), XPhos precatalyst (CAS 1028206-56-5; 24.24 mg, 0.033 mmol), sodium tert-butoxide (39.4 mg, 0.41 mmol), and toluene (1.5 mL). The mixture was stirred at 95° C. under nitrogen gas for 3 h. The reaction was then cond and the resulting residue was dissolved in DCM. This solution was washed with water, dried over magnesium sulfate, and cond. The resulting crude product was purified by flash-chromatography (silica gel, 0-85% EtOAc in hexanes), affording 5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)-N-(2-(methylsulfonyl)-5-morpholinophenyl)quinolin-4-amine as a white solid. Mass Spectrum (ESI) m/e=525.3 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 8.62 (1H, d, J=6.5 Hz), 8.55 (1H, d, J=5.1 Hz), 7.79 (1H, d, J=9.0 Hz), 7.67-7.70 (1H, m), 7.62-7.67 (1H, m), 7.18-7.25 (1H, m), 6.96-7.04 (1H, m), 6.47-6.52 (1H, m), 5.98-6.01 (1H, m), 3.70-3.80 (4H, m), 3.17 (3H, s), 3.06-3.16 (4H, m), 2.49 (3H, s), 2.28 (3H, s).

後処理

  1. washThis solution was washed with water
  2. dry with materialdried over magnesium sulfate, and cond
  3. customThe resulting crude product was purified by flash-chromatography (silica gel, 0-85% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-aff3f16703da40aca78551719ff43458
出典データセット
uspto-grants-2015_01
特許番号
US08940724B2

反応ノート

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