Triethylamine → 7-Acetyl-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

HRID 2361365Notes

Reaction equation

HRID 2361365 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[C:30](=[O:31])[C:29]6[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=6)[N:23]=[CH:22]5)[C:16]=4[CH3:32])=[CH:13][N:12]=[C:11]([C:33]([NH2:35])=[O:34])[C:7]=3[NH:8]2)=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:41]([O:43]CC)=[CH2:42])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:41]([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[C:30](=[O:31])[C:29]6[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=6)[N:23]=[CH:22]5)[C:16]=4[CH3:32])=[CH:13][N:12]=[C:11]([C:33]([NH2:35])=[O:34])[C:7]=3[NH:8]2)=[CH:4][CH:3]=1)(=[O:43])[CH3:42]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 619414Stannane, tributyl(1-ethoxyethenyl)-2×HCID 21226206Ethyl acetate hexaneHCID 679948327-Bromo-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

Product 1

HCID 679945647-Acetyl-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamideYield 48.9%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 7-bromo-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (0.198 g, 0.378 mmol), tributyl(1-ethoxyvinyl)stannane (0.299 mL, 0.906 mmol), bis(triphenylphosphine)palladium(II) chloride (0.037 g, 0.053 mmol), triethylamine (0.068 mL, 0.491 mmol) in 1,4-dioxane (Volume: 15 mL) was heated at 95° C. for 24 hr. No reaction occurred. The starting bromo compound remained unchanged. Upon cooling to room temperature, some yellow precipitate formed. The clear solution was transferred to a pressure tube. Additional tributyl(1-ethoxyvinyl)stannane (0.6 mL, 1.82 mmol), bis(triphenylphosphine)palladium(II) chloride (0.080 g, 0.114 mmol), and triethylamine (0.11 mL, 0.789 mmol) were added. The mixture 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 (30 mL) and stirred with 1 N HCl solution (10 mL) at room temperature for 2 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 (90 mg, 0.185 mmol, 48.9% yield) was isolated as a yellow solid by ISCO (24 g silica gel, solid loading, 60-90% ethyl acetate/hexane).

Workup

  1. temperatureUpon cooling to room temperature
  2. customsome yellow precipitate formed
  3. customThe clear solution was transferred to a pressure tube
  4. temperatureThe mixture was heated at 125° C. for 16 hr
  5. temperatureUpon cooling to room temperature
  6. filtrationthe reaction mixture was filtered through CELITE®
  7. concentrationthe filtrate was concentrated under vacuum
  8. additionThe residue was diluted with THF (30 mL)
  9. concentrationThe solution was concentrated under vacuum
  10. extractionextracted with ethyl acetate (3×40 mL)
  11. extractionThe combined extract
  12. dry with materialwas dried over anhydrous MgSO4

Sources & evidence

ORD record
ord-566e692d4dc84df38634ad494f6dbd30
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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