Cesium carbonate → N-(3-(6-Methoxy-5-(5-(4-methylpiperazin-1-yl)pyridin-2-ylamino)pyridine-3-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-carboxamide

HRID 557537노트

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HRID 557537 반응식
[NH2:1][C:2]1[CH:3]=[C:4]([C:10]2[C:11]([CH3:28])=[C:12]([NH:16][C:17]([C:19]3[S:23][C:22]4[CH2:24][CH2:25][CH2:26][CH2:27][C:21]=4[CH:20]=3)=[O:18])[CH:13]=[CH:14][CH:15]=2)[CH:5]=[N:6][C:7]=1[O:8][CH3:9].Cl[C:30]1[N:35]=[CH:34][C:33]([N:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]2)=[CH:32][CH:31]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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]>[CH3:9][O:8][C:7]1[N:6]=[CH:5][C:4]([C:10]2[C:11]([CH3:28])=[C:12]([NH:16][C:17]([C:19]3[S:23][C:22]4[CH2:24][CH2:25][CH2:26][CH2:27][C:21]=4[CH:20]=3)=[O:18])[CH:13]=[CH:14][CH:15]=2)=[CH:3][C:2]=1[NH:1][C:30]1[CH:31]=[CH:32][C:33]([N:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]2)=[CH:34][N:35]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59740583N-(3-(5-Amino-6-methoxypyridin-3-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamideHCID 753557481-(6-Chloropyridin-3-yl)-4-methylpiperazine

생성물 1

HCID 59740597N-(3-(6-Methoxy-5-(5-(4-methylpiperazin-1-yl)pyridin-2-ylamino)pyridine-3-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-carboxamide수율 50%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

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온도
95 °C

실험 절차

In a 48-mL seal tube equipped with a magnetic stirring bar was placed N-(3-(5-Amino-6-methoxypyridin-3-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide (17) (0.20 g, 0.5 mmol), 1-(6-chloro-pyridin-3-yl)-4-methyl-piperazine (0.11 g, 0.5 mmol), Pd2(dba)3 (0.046 g, 0.050 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.040 g, 0.070 mmol), and Cs2CO3 (0.33 g, 1.0 mmol) in dioxane (10 mL). After the mixture was degassed for 15 min., it was heated at 95° C. for 16 h. Then, the reaction mixture was cooled to room temperature and poured into H2O (10 mL). To this was added dichloromethane (10 mL) and the layers were separated. The aqueous phase was extracted with dichloromethane (3×10 mL), and the combined organic extracts were washed with H2O (5 mL) and brine (5 mL), dried (Na2SO4), and concentrated. The crude mixture was purified by column chromatography, gradient 0-33% MeOH in dichloromethane, to afford 0.140 g (50%) of N-(3-(6-Methoxy-5-(5-(4-methylpiperazin-1-yl)pyridin-2-ylamino)pyridine-3-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-carboxamide (18) as a solid.

후처리

  1. customIn a 48-mL seal tube
  2. customequipped with a magnetic stirring bar
  3. customAfter the mixture was degassed for 15 min.
  4. temperatureThen, the reaction mixture was cooled to room temperature
  5. additionpoured into H2O (10 mL)
  6. additionTo this was added dichloromethane (10 mL)
  7. customthe layers were separated
  8. extractionThe aqueous phase was extracted with dichloromethane (3×10 mL)
  9. washthe combined organic extracts were washed with H2O (5 mL) and brine (5 mL)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated
  12. customThe crude mixture was purified by column chromatography, gradient 0-33% MeOH in dichloromethane

출처 및 근거

ORD 기록
ord-fe95fb84c94d4895942ac86527f59e96
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08058446B2

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