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Stannanecarbonitrile, tributyl- → (2,5-Dimorpholinopyridin-3-ylamino)-3-methyl-2-(pyridin-2-yl)quinoline-8-carbonitrile

HRID 1431537
ノート
印刷プレビュー

反応式

HRID 1431537 の反応式
Cl[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1)[C:8]([CH3:18])=[C:7]2[NH:19][C:20]1[C:21]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)=[N:22][CH:23]=[C:24]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[CH:25]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C([Sn]([C:85]#[N:86])(CCCC)CCCC)CCC>CN1CCCC1=O.FC(F)(F)C([O-])=O.FC(F)(F)C([O-])=O.[Pd+2]>[O:35]1[CH2:34][CH2:33][N:32]([C:21]2[C:20]([NH:19][C:7]3[C:6]4[C:11](=[C:2]([C:85]#[N:86])[CH:3]=[CH:4][CH:5]=4)[N:10]=[C:9]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=4)[C:8]=3[CH3:18])=[CH:25][C:24]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[CH:23][N:22]=2)[CH2:37][CH2:36]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 200512Stannanecarbonitrile, tributyl-HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl2 回HCID 596314868-chloro-N-(2,5-dimorpholinopyridin-3-yl)-3-methyl-2-(pyridin-2-yl)quinolin-4-amine

生成物 1

HCID 59631330(2,5-Dimorpholinopyridin-3-ylamino)-3-methyl-2-(pyridin-2-yl)quinoline-8-carbonitrile

試薬・触媒・溶媒 2

HCID 2733347
Palladium(II) trifluoroacetate
触媒
2 回
HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
160 °C

実験手順

To a stirred solution of 8-chloro-N-(2,5-dimorpholinopyridin-3-yl)-3-methyl-2-(pyridin-2-yl)quinolin-4-amine (0.180 g, 0.35 mmol) in 1-methylpyrrolidin-2-one (3.46 mL) was added palladium bis(trifluoroacetate) (0.017 g, 0.052 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropyl-biphenyl (0.050 g, 0.11 mmol) followed by tri-n-butyltin cyanide (0.109 g, 0.35 mmol). The reaction was heated to 160° C. for 36 h. A further 0.3 eq of palladium bis(trifluoroacetate) and 0.6 eq of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine was added. The reaction was further heated at 160° C. for 3 h. After which, the reaction was cooled to 23° C. The crude product was filtered through a plug of alumina eluting with EtOAc. The organic layer was washed with water, dried over MgSO4 and filtered and evaporated in vacuo. The crude product was purified by column chromatography on alumina (0 to 50% EtOAc/hexane)) to give the desired product 4-((2,5-dimorpholinopyridin-3-ylamino)-3-methyl-2-(pyridin-2-yl)quinoline-8-carbonitrile. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.72 (1H, ddd, J=4.8, 1.8, 1.0 Hz), 8.29 (1H, dd, J=7.1, 1.3 Hz), 8.19 (1H, dd, J=8.5, 1.3 Hz), 8.03-8.08 (2H, m), 7.96 (1H, dt, J=7.9, 1.1 Hz), 7.61-7.65 (2H, m), 7.53 (1H, ddd, J=7.6, 4.8, 1.3 Hz), 6.55 (1H, d, J=2.7 Hz), 3.65 (4H, m), 3.39 (4H, m), 2.95 (4H, m), 2.88 (4H, m), 2.19 (3H, s). Mass Spectrum (ESI) m/e=508.3 (M+1).

後処理

  1. temperatureThe reaction was further heated at 160° C. for 3 h
  2. temperatureAfter which, the reaction was cooled to 23° C
  3. filtrationThe crude product was filtered through a plug of alumina eluting with EtOAc
  4. washThe organic layer was washed with water
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe crude product was purified by column chromatography on alumina (0 to 50% EtOAc/hexane))

出典と根拠

ORDレコード
ord-50c97e3a8c554dfcaa08cc446da7a903
出典データセット
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08940724B2

反応ノート

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