Stannanecarbonitrile, tributyl- → 3-Methyl-2-(4-methylpyridin-2-yl)-4-(5-morpholinopyridin-3-ylamino)-quinoline-8-carbonitrile

HRID 1431540노트

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HRID 1431540 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[CH:71]=[N:72][CH:73]=[C:74]([N:76]2[CH2:81][CH2:80][O:79][CH2:78][CH2:77]2)[CH:75]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:68][C:57]1[C:58]([C:61]2[CH:66]=[C:65]([CH3:67])[CH:64]=[CH:63][N:62]=2)=[N:59][C:60]2[C:55]([C:56]=1[NH:69][C:70]1[CH:71]=[N:72][CH:73]=[C:74]([N:76]3[CH2:81][CH2:80][O:79][CH2:78][CH2:77]3)[CH:75]=1)=[CH:54][CH:53]=[CH:52][C:51]=2[C:48]#[N:49]

참가 물질

7

반응물 4

HCID 200512Stannanecarbonitrile, tributyl-HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596311068-chloro-3-methyl-2-(4-methylpyridin-2-yl)-N-(5-morpholinopyridin-3-yl)quinolin-4-amine

생성물 1

HCID 574497763-Methyl-2-(4-methylpyridin-2-yl)-4-(5-morpholinopyridin-3-ylamino)-quinoline-8-carbonitrile

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

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온도
100 °C

실험 절차

To a stirred solution of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.025 g, 0.053 mmol), tri-n-butyltin cyanide (0.104 g, 0.33 mmol), 8-chloro-3-methyl-2-(4-methylpyridin-2-yl)-N-(5-morpholinopyridin-3-yl)quinolin-4-amine (0.15 g, 0.33 mmol) and Pd2dba3 (0.012 g, 0.013 mmol) in toluene (3.30 mL) was added sodium tert-butoxide (0.079 g, 0.82 mmol). The reaction mixture was heated to 100° C. for 66 h. After which, the reaction mixture 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 3-methyl-2-(4-methylpyridin-2-yl)-4-(5-morpholinopyridin-3-ylamino)quinoline-8-carbonitrile. 1H NMR (400 MHz, CD2Cl2) δ ppm 8.59 (1H, d, J=5.5 Hz), 8.06 (2H, ddd, J=14.8, 7.9, 1.4 Hz), 7.86 (1H, d, J=2.5 Hz), 7.78-7.83 (1H, m), 7.67 (1H, d, J=2.3 Hz), 7.48 (1H, dd, J=8.5, 7.1 Hz), 7.27 (1H, m), 6.60 (1H, s), 6.43 (1H, t, J=2.3 Hz), 3.75 (4H, m), 3.05 (4H, m), 2.51 (3H, s), 2.36 (3H, s). Mass Spectrum (ESI) m/e=437.1 (M+1).

후처리

  1. filtrationAfter which, the reaction mixture 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-6336e1e2e41d4131b0a2f4382d33da76
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940724B2

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