Triethylamine → methyl 9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indole-3-carboxylate

HRID 1473256Notes

Reaction equation

HRID 1473256 reaction equation
[F:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]3[C:16](O)=[C:17]([C:22]([O:24][CH3:25])=[O:23])[N:18]([CH3:21])[C:19](=[O:20])[C:8]2=3)=[CH:4][CH:3]=1.CCN(CC)CC.O(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O.C([O-])(O)=O.[Na+].[CH3:56][C:57]1[CH:62]=[CH:61][C:60](B(O)O)=[CH:59][CH:58]=1.C([O-])([O-])=O.[Na+].[Na+].[NH4+].[Cl-]>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]3[C:16]([C:60]4[CH:61]=[CH:62][C:57]([CH3:56])=[CH:58][CH:59]=4)=[C:17]([C:22]([O:24][CH3:25])=[O:23])[N:18]([CH3:21])[C:19](=[O:20])[C:8]2=3)=[CH:4][CH:3]=1

Participants

10

Reactant 7

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 25517Ammonium ChlorideHCID 67749Trifluoromethanesulfonic anhydrideHCID 79799Tolylboronic acidHCID 516892Sodium BicarbonateHCID 89462487methyl 9-(4-fluorobenzyl)-4-hydroxy-2-methyl-1-oxo-2,9-dihydro-1H-pyrido[3,4-b]indole-3-carboxylate

Product 1

HCID 89462632methyl 9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indole-3-carboxylateYield 47.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

An ice cold solution of methyl 9-(4-fluorobenzyl)-4-hydroxy-2-methyl-1-oxo-2,9-dihydro-1H-pyrido[3,4-b]indole-3-carboxylate (1.1 g, 2.89 mmol) and Et3N (2.004 ml, 14.46 mmol) in DCM (30 mL) was treated with Tf2O (0.977 ml, 5.78 mmol). After 15 min, the reaction mixture was poured into sat. aq. NaHCO3 and extracted with EtOAc. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The crude residue was dissolved in 1,4-Dioxane (9.57 ml)/Water (1.913 ml), treated with 4-methylphenyl boronic acid (0.550 g, 4.05 mmol) and Na2CO3 (0.920 g, 8.68 mmol) and then degassed with N2 for 5 min. Pd(PPh3)4 (0.334 g, 0.289 mmol) was added and the reaction mixture was warmed to 80° C. After 2 h, the reaction mixture was poured into sat. aq. NH4Cl and extracted with EtOAc. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. the residue was purified by ISCO (0-50% EtOAc-hexanes) to afford methyl 9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indole-3-carboxylate (625 mg, 1.375 mmol, 47.6% yield) as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d)=7.31 (d, J=3.9 Hz, 6H), 7.22 (none, 2H), 6.96 (s, 4H), 6.15 (s, 2H), 3.70 (s, 3H), 3.59 (s, 3H), 2.48 (s, 3H).

Workup

  1. extractionextracted with EtOAc
  2. washThe organic phase was washed with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe crude residue was dissolved in 1,4-Dioxane (9.57 ml)/Water (1.913 ml)
  7. customdegassed with N2 for 5 min
  8. waitAfter 2 h
  9. extractionextracted with EtOAc
  10. dry with materialThe organic layer was dried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customthe residue was purified by ISCO (0-50% EtOAc-hexanes)

Sources & evidence

ORD record
ord-3e9a145a7be64c348298591c1a3461b4
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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