Potassium Phosphate, Tribasic → methyl 8-chloro-7-methoxy-2-(4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxylate

HRID 2410731Notes

Reaction equation

HRID 2410731 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2[C:14]2[C:19]([O:20][CH3:21])=[CH:18][CH:17]=[CH:16][C:15]=2OC)CCCCC1.COC1C=CC(B(O)O)=CC=1.Br[C:42]1[CH:43]=[C:44]([C:58]([O:60][CH3:61])=[O:59])[C:45]2[NH:46][C:47]3[CH:48]=[C:49]([O:56][CH3:57])[C:50]([Cl:55])=[CH:51][C:52]=3[C:53]=2[N:54]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:55][C:50]1[C:49]([O:56][CH3:57])=[CH:48][C:47]2[NH:46][C:45]3[C:44]([C:58]([O:60][CH3:61])=[O:59])=[CH:43][C:42]([C:16]4[CH:15]=[CH:14][C:19]([O:20][CH3:21])=[CH:18][CH:17]=4)=[N:54][C:53]=3[C:52]=2[CH:51]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 201262(4-Methoxyphenyl)boronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86663015methyl 2-bromo-8-chloro-7-methoxy-5H-pyrido[3,2-b]indole-4-carboxylate

Product 1

HCID 66604816methyl 8-chloro-7-methoxy-2-(4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxylateYield 487.2%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
80 °C

Procedure

A vial containing dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (6 mg, 0.015 mmol), 4-methoxyphenylboronic acid (14 mg, 0.093 mmol), methyl 2-bromo-8-chloro-7-methoxy-5H-pyrido[3,2-b]indole-4-carboxylate (29 mg, 0.077 mmol), palladium(II) acetate (1.7 mg, 7.7 μmol), and potassium phosphate tribasic (49.1 mg, 0.231 mmol) was flushed with nitrogen. Tetrahydrofuran (1 mL) was added and the reaction was heated at 80° C. overnight. The reaction was partitioned between EtOAc and water. The organic phase was separated, washed with brine, dried with sodium sulfate, and the solvents removed. Radial silica gel chromatography (elution with DCM) afforded methyl 8-chloro-7-methoxy-2-(4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxylate (29 mg). MS (ESI) m/z 397.0 (M+H). 1H NMR (CDCl3) δ ppm 9.31 (1H, s), 8.31 (1H, s), 8.00-8.12 (3H, m), 6.99-7.07 (2H, m), 6.90 (1H, s), 4.03 (3H, s), 3.96 (3H, s), 3.88 (3H, s).

Workup

  1. customwas flushed with nitrogen
  2. additionTetrahydrofuran (1 mL) was added
  3. customThe reaction was partitioned between EtOAc and water
  4. customThe organic phase was separated
  5. washwashed with brine
  6. dry with materialdried with sodium sulfate
  7. customthe solvents removed
  8. washRadial silica gel chromatography (elution with DCM)

Sources & evidence

ORD record
ord-13c70ab19bb24840948bccf4af426e52
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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