4-Bromopyrimidine → 2,8-dimethyl-5-(pyrimidin-4-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1400644Notes

Reaction equation

HRID 1400644 reaction equation
[C:1]([N:3]1[C:11]2[CH:10]=[CH:9][C:8]([CH3:12])=[CH:7][C:6]=2[C:5]2[CH2:13][N:14]([CH3:17])[CH2:15][CH2:16][C:4]1=2)#[CH:2].Br[C:19]1[CH:24]=[CH:23][N:22]=[CH:21][N:20]=1>C(N(CC)CC)C.[Cu](I)I>[CH3:17][N:14]1[CH2:15][CH2:16][C:4]2[N:3]([C:1]#[C:2][C:19]3[CH:24]=[CH:23][N:22]=[CH:21][N:20]=3)[C:11]3[CH:10]=[CH:9][C:8]([CH3:12])=[CH:7][C:6]=3[C:5]=2[CH2:13]1

Participants

5

Reactant 2

HCID 127522204-BromopyrimidineHCID 594550005-Ethynyl-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 594550372,8-dimethyl-5-(pyrimidin-4-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoleYield 17.7%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
40 °C

Procedure

5-Ethynyl-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (100 mg, 0.466 mmol) and 4-bromopyrimidine (126 mg, 0.797 mmol) were dissolved in triethylamine (1.5 mL), and the solution was purged with nitrogen. Dichlorobis (triphenylphosphine) palladium (12.5 mg, 0.017 mmol) and copper iodide (6.7 mg, 0.035 mmol) were added and the reaction mixture was purged again with nitrogen. The reaction mixture was heated by microwave at 40° C. for 90 min. The reaction mixture was quenched with 30 mL water and extracted with EtOAc (3×15 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to obtain crude product. The crude product was purified with column chromatography (silica gel: 100-200 mesh, eluent 0-10% MeOH in DCM) to obtain 25 mg product. 1H NMR (CDCl3, freebase) δ (ppm): 9.17 (s, 1H), 8.76 (d, 1H), 7.57 (d, 1H), 7.40 (d, 1H), 7.18 (m, 2H), 3.64 (s, 2H), 3.06 (d, 2H), 2.98 (d, 2H), 2.61 (s, 3H), 2.43 (s, 3H).

Workup

  1. customthe solution was purged with nitrogen
  2. customthe reaction mixture was purged again with nitrogen
  3. customThe reaction mixture was quenched with 30 mL water
  4. extractionextracted with EtOAc (3×15 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto obtain crude product
  8. customThe crude product was purified with column chromatography (silica gel: 100-200 mesh, eluent 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-d7a6c9e5539e448097fef8aef7cdf3eb
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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