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

HRID 1431541Notes

Reaction equation

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

Participants

Conditions

Temperature: 100 °C

Procedure

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).

Workup

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

Sources & evidence

ORD record: ord-5eeaa140d9364d70b9a756c33461ba24
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940724B2

Reaction notes

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