Triethylamine → 7-Acetyl-4-(3-(6-methoxy-1-oxoisoindolin-2-yl)-2-methylphenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

HRID 2361370Notes

Reaction equation

HRID 2361370 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[C:14]([C:15]4[CH:20]=[CH:19][CH:18]=[C:17]([N:21]5[CH2:29][C:28]6[C:23](=[CH:24][C:25]([O:30][CH3:31])=[CH:26][CH:27]=6)[C:22]5=[O:32])[C:16]=4[CH3:33])=[CH:13][N:12]=[C:11]([C:34]([NH2:36])=[O:35])[C:7]=3[NH:8]2)=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:42]([O:44]CC)=[CH2:43])CCC.C(N(CC)CC)C.C(OCC)(=O)C.CCCCCC>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:42]([C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[C:14]([C:15]4[CH:20]=[CH:19][CH:18]=[C:17]([N:21]5[CH2:29][C:28]6[C:23](=[CH:24][C:25]([O:30][CH3:31])=[CH:26][CH:27]=6)[C:22]5=[O:32])[C:16]=4[CH3:33])=[CH:13][N:12]=[C:11]([C:34]([NH2:36])=[O:35])[C:7]=3[NH:8]2)=[CH:4][CH:3]=1)(=[O:44])[CH3:43]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 21226206Ethyl acetate hexaneHCID 679947687-Bromo-4-(3-(6-methoxy-1-oxoisoindolin-2-yl)-2-methylphenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

Product 1

HCID 679946867-Acetyl-4-(3-(6-methoxy-1-oxoisoindolin-2-yl)-2-methylphenyl)-9H-pyrido[3,4-b]indole-1-carboxamideYield 60.7%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 7-bromo-4-(3-(6-methoxy-1-oxoisoindolin-2-yl)-2-methylphenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (0.198 g, 0.366 mmol), tributyl(1-ethoxyvinyl)stannane (0.301 mL, 0.914 mmol), bis(triphenylphosphine)palladium(II) chloride (0.039 g, 0.055 mmol), triethylamine (0.071 mL, 0.512 mmol) in 1,4-Dioxane (12 mL) was heated at 125° C. for 16 hr. Upon cooling to room temperature, the reaction mixture was filtered through CELITE®, and the filtrate was concentrated under vacuum. The residue was diluted with THF (40 mL) and stirred with 1 N HCl solution (10 mL) at 50° C. for 1 hr. The solution was concentrated under vacuum, basified with 1 N NaOH solution, and extracted with ethyl acetate (3×40 mL). The combined extract was dried over anhydrous MgSO4. The desired product (0.112 g, 0.222 mmol, 60.7% yield) was isolated as a pale yellow solid by ISCO (40 g silica gel, solid loading, 50-90% ethyl acetate/hexane).

Workup

  1. temperatureUpon cooling to room temperature
  2. filtrationthe reaction mixture was filtered through CELITE®
  3. concentrationthe filtrate was concentrated under vacuum
  4. additionThe residue was diluted with THF (40 mL)
  5. concentrationThe solution was concentrated under vacuum
  6. extractionextracted with ethyl acetate (3×40 mL)
  7. extractionThe combined extract
  8. dry with materialwas dried over anhydrous MgSO4

Sources & evidence

ORD record
ord-ee27b0d471d54f8585f8b886d534754f
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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