Potassium Phosphate, Tribasic → methyl 7-(morpholine-4-carbonyl)-2-phenyl-5H-pyrido[3,2-b]indole-4-carboxylate

HRID 2410750Notes

Reaction equation

HRID 2410750 reaction equation
[C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:11]1[CH:12]=[C:13]([C:32]([O:34][CH3:35])=[O:33])[C:14]2[NH:15][C:16]3[CH:17]=[C:18]([C:24]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[O:25])[CH:19]=[CH:20][C:21]=3[C:22]=2[N:23]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:26]1([C:24]([C:18]2[CH:19]=[CH:20][C:21]3[C:22]4[N:23]=[C:11]([C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)[CH:12]=[C:13]([C:32]([O:34][CH3:35])=[O:33])[C:14]=4[NH:15][C:16]=3[CH:17]=2)=[O:25])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 66827Phenylboronic AcidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86663021methyl 2-bromo-7-(morpholine-4-carbonyl)-5H-pyrido[3,2-b]indole-4-carboxylate

Product 1

HCID 66604852methyl 7-(morpholine-4-carbonyl)-2-phenyl-5H-pyrido[3,2-b]indole-4-carboxylateYield 75.1%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
80 °C

Procedure

A mixture of phenylboronic acid (92 mg, 0.75 mmol), methyl 2-bromo-7-(morpholine-4-carbonyl)-5H-pyrido[3,2-b]indole-4-carboxylate (150 mg, 0.359 mmol), finely powdered potassium phosphate tribasic (183 mg, 0.861 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (56.8 mg, 0.119 mmol), and palladium(II) acetate (11 mg, 0.047 mmol) in a vial was flushed with nitrogen. Tetrahydrofuran (3 mL) was added and the reaction was heated at 80° C. overnight. It was partitioned between water and methylene chloride. The organic phase was separated, washed with brine, and dried over sodium sulfate. Removal of the solvents followed by radial silica gel chromatography (step gradient elution with methylene chloride containing 0 to 2% MeOH) afforded methyl 7-(morpholine-4-carbonyl)-2-phenyl-5H-pyrido[3,2-b]indole-4-carboxylate (112 mg) as a solid. MS (ESI) m/z 416.1 (M+H). 1H NMR (CDCl3) δ ppm 9.82 (1H, s), 8.40 (1H, d, J=7.93 Hz), 8.25 (1H, s), 8.12 (2H, d, J=7.63 Hz), 7.60 (1H, s), 7.48 (2H, t, J=7.63 Hz), 7.36-7.42 (1H, m), 7.32 (1H, d, J=7.93 Hz), 4.03 (3H, s), 3.38-3.95 (8H, m).

Workup

  1. customwas flushed with nitrogen
  2. additionTetrahydrofuran (3 mL) was added
  3. customIt was partitioned between water and methylene chloride
  4. customThe organic phase was separated
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. customRemoval of the solvents
  8. washfollowed by radial silica gel chromatography (step gradient elution with methylene chloride containing 0 to 2% MeOH)

Sources & evidence

ORD record
ord-f0c44e9e3a6c4eeda62574b7aa98c449
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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