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

HRID 1431541ノート

反応式

HRID 1431541 の反応式
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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-5eeaa140d9364d70b9a756c33461ba24
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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