Cesium carbonate → N-[3-(5-{[5-(1,4-dimethyl-3-oxopiperazin-2-yl)pyridin-2-yl]amino}-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide

HRID 1363516Notes

Reaction equation

HRID 1363516 reaction equation
[NH2:1][C:2]1[C:7](=[O:8])[N:6]([CH3:9])[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]=1.Cl[C:30]1[N:35]=[CH:34][C:33]([CH:36]2[N:41]([CH3:42])[CH2:40][CH2:39][N:38]([CH3:43])[C:37]2=[O:44])=[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]>[CH3:42][N:41]1[CH2:40][CH2:39][N:38]([CH3:43])[C:37](=[O:44])[CH:36]1[C:33]1[CH:32]=[CH:31][C:30]([NH:1][C:2]2[C:7](=[O:8])[N:6]([CH3:9])[CH:5]=[C:4]([C:10]3[C:11]([CH3:28])=[C:12]([NH:16][C:17]([C:19]4[S:23][C:22]5[CH2:24][CH2:25][CH2:26][CH2:27][C:21]=5[CH:20]=4)=[O:18])[CH:13]=[CH:14][CH:15]=3)[CH:3]=2)=[N:35][CH:34]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 57625113N-(3-(5-Amino-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamideHCID 576251793-(6-Chloropyridin-3-yl)-1,4-dimethylpiperazin-2-one

Product 1

HCID 57625085N-[3-(5-{[5-(1,4-dimethyl-3-oxopiperazin-2-yl)pyridin-2-yl]amino}-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamideYield 34%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A 48-mL sealed tube equipped with a magnetic stirring bar was charged with 43 (0.20 g, 0.5 mmol), 3-(6-chloropyridin-3-yl)-1,4-dimethylpiperazin-2-one (0.185 g, 0.8 mmol), Pd2(dba)3 (0.032 g, 0.035 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.030 g, 0.05 mmol), and Cs2CO3 (0.326 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 0-10%, MeOH in dichloromethane/ether (1/1), to afford 0.10 g (34%) of 44 as a solid; MS (ESI+) m/z 596 (M+H).

Workup

  1. customA 48-mL sealed 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 0-10%, MeOH in dichloromethane/ether (1/1)

Sources & evidence

ORD record
ord-60b02ad87b8c478393b030618bedb7ed
Source dataset
uspto-grants-2011_02
Patent number
US07884108B2

Reaction notes

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