Stannanecarbonitrile, tributyl- → 4-(5'-Methoxy-5-morpholino-2,3'-bipyridin-3-ylamino)-3-methyl-2-(4-methylpyridin-2-yl)quinoline-8-carbonitrile

HRID 1431541노트

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HRID 1431541 반응식
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C([Sn]([C:48]#[N:49])(CCCC)CCCC)CCC.Cl[C:51]1[CH:52]=[CH:53][CH:54]=[C:55]2[C:60]=1[N:59]=[C:58]([C:61]1[CH:66]=[C:65]([CH3:67])[CH:64]=[CH:63][N:62]=1)[C:57]([CH3:68])=[C:56]2[NH:69][C:70]1[C:71]([C:82]2[CH:83]=[N:84][CH:85]=[C:86]([O:88][CH3:89])[CH:87]=2)=[N:72][CH:73]=[C:74]([N:76]2[CH2:81][CH2:80][O:79][CH2:78][CH2:77]2)[CH:75]=1>CN1CCCC1=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:89][O:88][C:86]1[CH:87]=[C:82]([C:71]2[C:70]([NH:69][C:56]3[C:55]4[C:60](=[C:51]([C:48]#[N:49])[CH:52]=[CH:53][CH:54]=4)[N:59]=[C:58]([C:61]4[CH:66]=[C:65]([CH3:67])[CH:64]=[CH:63][N:62]=4)[C:57]=3[CH3:68])=[CH:75][C:74]([N:76]3[CH2:77][CH2:78][O:79][CH2:80][CH2:81]3)=[CH:73][N:72]=2)[CH:83]=[N:84][CH:85]=1

참가 물질

6

반응물 3

HCID 200512Stannanecarbonitrile, tributyl-HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 509080438-chloro-N-(5'-methoxy-5-morpholino-2,3'-bipyridin-3-yl)-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-amine

생성물 1

HCID 509080424-(5'-Methoxy-5-morpholino-2,3'-bipyridin-3-ylamino)-3-methyl-2-(4-methylpyridin-2-yl)quinoline-8-carbonitrile

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 13387N-methyl-2-pyrrolidone용매

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온도
100 °C

실험 절차

To a stirred solution of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (1.9 mg, 4.05 μmol), tri-n-butyltin cyanide (8.00 mg, 0.025 mmol), 8-chloro-N-(5′-methoxy-5-morpholino-2,3′-bipyridin-3-yl)-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-amine (0.014 g, 0.025 mmol) in 1-methylpyrrolidin-2-one (2.0 mL) was added Pd2dba3 (0.927 mg, 1.01 μmol). The reaction mixture was heated to 100° C. and stirred for 21.5 h. The crude product was filtered through a plug of alumina eluting with EtOAc. The filtrate was cond in vacuo. The crude product was purified by column chromatography on alumina (0 to 50% EtOAc in hexanes) to give the desired product. The desired product was further purified with HPLC (10-90% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution). The desired fractions were cond then diluted with EtOAc. After washing twice with satd aq. sodium bicarbonate solution, the solvent was removed under reduced pressure to yield pure product 4-(5′-methoxy-5-morpholino-2,3′-bipyridin-3-ylamino)-3-methyl-2-(4-methylpyridin-2-yl)quinoline-8-carbonitrile. 1H NMR (400 MHz, CD2Cl2) δ ppm 8.53 (1H, d, J=5.1 Hz), 8.42 (1H, d, J=1.8 Hz), 8.30 (1H, d, J=2.7 Hz), 8.06-8.15 (2H, m), 7.97 (1H, s), 7.84 (1H, m), 7.56 (1H, dd, J=8.4, 7.2 Hz), 7.39 (1H, dd, J=2.8, 1.9 Hz), 7.24 (1H, m), 6.30 (1H, br. s.), 5.47 (1H, s), 3.90 (3H, s), 3.64 (4H, t, J=4.9 Hz), 3.25 (4H, br. s.), 2.50 (3H, s), 2.43 (3H, s). Mass Spectrum (ESI) m/e=544.2 (M+1).

후처리

  1. filtrationThe crude product was filtered through a plug of alumina eluting with EtOAc
  2. customThe crude product was purified by column chromatography on alumina (0 to 50% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-5eeaa140d9364d70b9a756c33461ba24
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940724B2

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