Potassium Carbonate → methyl 5-((4-fluorophenyl)ethynyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxylate

HRID 1401691Notes

Reaction equation

HRID 1401691 reaction equation
[CH3:1][N:2]1[CH2:18][CH2:17][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.C(=O)([O-])[O-].[K+].[K+].Br[C:26]#[C:27][C:28]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=1>C1(C)C=CC=CC=1.S([O-])([O-])(=O)=O.[Cu+2]>[F:34][C:31]1[CH:32]=[CH:33][C:28]([C:27]#[C:26][N:6]2[C:7]3[CH:8]=[CH:9][C:10]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:12]=3[C:4]3[CH2:3][N:2]([CH3:1])[CH2:18][CH2:17][C:5]2=3)=[CH:29][CH:30]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 1070332Methyl 2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxylateHCID 111483184-Fluorophenylethynyl bromide2×

Product 1

HCID 59455226methyl 5-((4-fluorophenyl)ethynyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxylate

Reagents, catalysts & solvents 2

HCID 24462Copper SulfateCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
82.5 °C

Procedure

Methyl 2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole-8-carboxylate (122 mg, 0.5 mmol) was dissolved in toluene (3 mL) and stirred for 10 min. Potassium carbonate (138 mg, 1.0 mmol), copper sulfate (124 mg, 0.05 mmol) and 1,10-phenanthraline (18 mg, 0.1 mmol) were added. The reaction mixture was stirred for 10 min. A solution of 1-(bromoethynyl)-4-fluorobenzene (110 mg, 0.11 mmol) in toluene (2 mL) was added to the reaction mixture, which was heated to 80-85° C. overnight. TLC monitoring showed 10% conversion of reactant to product. As such, more of 1-(bromoethynyl)-4-fluorobenzene (110 mg, 0.5 mmol) was added and heating was continued for 10-12 h. Toluene was removed under reduced pressure to obtain the product, which was purified by column chromatography using silica (100-200 mesh) and 0-5% DCM:MeOH as eluent. The pure compound was converted to its oxalate salt. 1H NMR (CD3OD, oxalate salt) δ (ppm): 8.30 (d, 1H), 8.05 (m, 1H), 7.78 (d, 1H), 7.62 (m, 2H), 7.20 (m, 2H), 3.95 (s, 3H), 3.80 (m, 2H), 3.70 (m, 2H), 3.35 (m, 2H), 3.15 (s, 3H).

Workup

  1. stirringThe reaction mixture was stirred for 10 min
  2. temperatureheating
  3. waitwas continued for 10-12 h
  4. customToluene was removed under reduced pressure
  5. customto obtain the product, which
  6. customwas purified by column chromatography

Sources & evidence

ORD record
ord-4dabbc62caa04c4a9127e02eff89c674
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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