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

HRID 1431603노트

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HRID 1431603 반응식
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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 54751079XPhos Palladacycle촉매HCID 6344Dichloromethane용매

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온도
95 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-aff3f16703da40aca78551719ff43458
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940724B2

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