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

HRID 1431604ノート

反応式

HRID 1431604 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]=[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

参加物

7

反応物 4

HCID 1140TolueneHCID 23676156Sodium t-butoxideHCID 265977632-Methylsulfonyl-5-(morpholin-4-yl)anilineHCID 596310374-Chloro-5,7-difluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)quinoline

生成物 1

HCID 509071835,7-difluoro-3-methyl-N-(2-(methylsulfonyl)-5-morpholinophenyl)-2-(2-(methylsulfonyl)phenyl)quinolin-4-amine

試薬・触媒・溶媒 2

HCID 54751079XPhos Palladacycle触媒HCID 8857Ethyl Acetate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-(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).

後処理

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

出典と根拠

ORDレコード
ord-da7196ec7ca1438185a9a87bc91af592
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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