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

HRID 2361408Notes

Reaction equation

HRID 2361408 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])=[C:13]([CH3:33])[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>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[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])=[C:13]([CH3:33])[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

6

Reactant 3

HCID 8471TriethylamineHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 679948107-bromo-3-methyl-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

Product 1

HCID 679951397-acetyl-3-methyl-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamideYield 54.3%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a well degassed mixture of 7-bromo-3-methyl-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (0.101 g, 0.188 mmol) and Bis(triphenylphosphine)palladium(II) chloride (0.018 g, 0.026 mmol) in 1,4-dioxane (2.0 mL) in a sealed tube was added tributyl(1-ethoxyvinyl)stannane (0.148 mL, 0.450 mmol) followed by triethylamine (0.052 mL, 0.375 mmol). The resulting mixture was evacuated and charged with nitrogen (2×), immersed in an oil bath at 100° C., and stirred overnight. The mixture was diluted with ethyl acetate, filtered through a pad of CELITE®, and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (5 mL) and stirred with 1 N aqueous hydrochloric acid (2 mL) for 2 h. The solution was concentrated under reduced pressure, and the residue was suspended in water. The pH was adjusted to ˜6 with 1 N sodium bicarbonate, and the suspension was extracted with ethyl acetate (3×). The combined organic layers were washed with brine and dried over anhydrous sodium sulfate. Concentration under reduced pressure followed by purification by flash silica gel chromatography using a mixture of ethyl acetate and hexane (50%-62%-75%-88%) afforded 7-acetyl-3-methyl-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (0.051 g, 0.102 mmol, 54% yield) as a pale yellow solid. LC/MS M+1=502.1.

Workup

  1. customTo a well degassed
  2. customThe resulting mixture was evacuated
  3. additioncharged with nitrogen (2×)
  4. customimmersed in an oil bath at 100° C.
  5. additionThe mixture was diluted with ethyl acetate
  6. filtrationfiltered through a pad of CELITE®
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
  9. stirringstirred with 1 N aqueous hydrochloric acid (2 mL) for 2 h
  10. concentrationThe solution was concentrated under reduced pressure
  11. extractionthe suspension was extracted with ethyl acetate (3×)
  12. washThe combined organic layers were washed with brine
  13. dry with materialdried over anhydrous sodium sulfate
  14. concentrationConcentration under reduced pressure
  15. customfollowed by purification by flash silica gel chromatography
  16. additiona mixture of ethyl acetate and hexane (50%-62%-75%-88%)

Sources & evidence

ORD record
ord-ab0f1c2532c74547bb682396caeba48d
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

Loading…