Triethylamine → HCID 22396596, compound

HRID 1356353Notes

Reaction equation

HRID 1356353 reaction equation
Br[C:2]1[C:3]2[C:4]3[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11][C:5]=3[NH:6][C:7]=2[CH:8]=[CH:9][CH:10]=1.CCN(CC)CC.[CH3:30][C:31]1([CH3:38])[C:35]([CH3:37])([CH3:36])[O:34][BH:33][O:32]1>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.O1CCOCC1>[CH3:30][C:31]1([CH3:38])[C:35]([CH3:37])([CH3:36])[O:34][B:33]([C:2]2[C:3]3[C:4]4[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11][C:5]=4[NH:6][C:7]=3[CH:8]=[CH:9][CH:10]=2)[O:32]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolaneHCID 22396611HCID 22396611, compound

Product 1

HCID 22396596HCID 22396596, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

tert-Butyl 10-bromo-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (1.51 g, 4.12 mmol) and dioxane (26 mL) were combined at rt under N2. Et3N (3.43 mL, 2.49 g, 24.6 mmol) and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.28 mL, 1.05 g, 8.21 mmol) were added to the mixture by syringe. trans-Dichlorobis(triphenylphosphine)palladium(II) (0.147 g, 0.209 mmol) was added and Ar was bubbled through the reaction mixture for 15 min. The reaction mixture was refluxed under N2 for 16 h. The cooled reaction mixture was concentrated and the residue was combined with toluene (50 mL), brine (20 mL) and H2O (100 mL). The layers were separated and the aqueous layer was extracted with toluene (2 ×50 mL). The combined organic extracts were washed with brine (40 mL), dried over MgSO4, filtered and concentrated. The crude product (1.90 g) was chromatographed (SiO2 60 g, eluted with 2:2:1 heptane:CH2Cl2:Et2O) to give tert-butyl 10-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (1.57 g) in 93% yield. MS (ESI+) for C23H33BN2O4 m/z 413.2 (M+H)+.

Workup

  1. customwere combined at rt under N2
  2. customAr was bubbled through the reaction mixture for 15 min
  3. temperatureThe reaction mixture was refluxed under N2 for 16 h
  4. customThe cooled reaction mixture
  5. concentrationwas concentrated
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with toluene (2 ×50 mL)
  8. washThe combined organic extracts were washed with brine (40 mL)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude product (1.90 g) was chromatographed
  13. wash(SiO2 60 g, eluted with 2:2:1 heptane:CH2Cl2:Et2O)

Sources & evidence

ORD record
ord-3617cffa30a648728c643b345473a893
Source dataset
uspto-grants-2003_07
Patent number
US06586421B2

Reaction notes

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