Triethylamine → 4-bromo-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-1H-indole-6-carbonitrile

HRID 2421237Notes

Reaction equation

HRID 2421237 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[N:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[CH2:13]([O:20][C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][C:22]=1[F:30])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(N(CC)CC)C>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[N:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[C:24]1[CH:25]=[CH:26][C:21]([O:20][CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[C:22]([F:30])[CH:23]=1

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 27377884-Benzyloxy-3-fluorophenylboronic Acid2×HCID 247288834-bromo-1H-indole-6-carbonitrile

Product 1

HCID 671360974-bromo-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-1H-indole-6-carbonitrileYield 63.1%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-bromo-6-cyanoindole (900 mg, 4.1 mmol) in dichloromethane (30 mL) was added 4-benzyloxy-3-fluorobenzeneboronic acid (2.0 g, 8.1 mmol), triethylamine (1.2 mL, 8.6 mmol), copper (II) acetate (1.5 g, 8.2 mmol) and powdered 4A molecular sieves (2.0 g). The reaction mixture was stirred at room temperature in the presence of air for 16 hours. Further quantities of 4-benzyloxy-3-fluorobenzeneboronic acid (500 mg), triethylamine (0.3 mL) and copper acetate (375 mg) were added and the mixture stirred at room temperature in the presence of air for a further 16 hours. The mixture was filtered and the solid washed with dichloromethane. The filtrate was concentrated at reduced pressure. The product was purified by silica gel chromatography eluting with 2-40% ethyl acetate in hexane to yield the title compound (D13), (1.09 g).

Workup

  1. stirringthe mixture stirred at room temperature in the presence of air for a further 16 hours
  2. filtrationThe mixture was filtered
  3. washthe solid washed with dichloromethane
  4. concentrationThe filtrate was concentrated at reduced pressure
  5. customThe product was purified by silica gel chromatography
  6. washeluting with 2-40% ethyl acetate in hexane

Sources & evidence

ORD record
ord-4a8dfc6eb62a4692b56e02a4beec653c
Source dataset
uspto-grants-2011_06
Patent number
US07956083B2

Reaction notes

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