Triethylamine → 3-Methyl-6-(pyridin-3-ylethynyl)pyridazine

HRID 902089

Reaction equation

HRID 902089 reaction equation
C[Si]([C:5]#[C:6][C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1)(C)C.Cl[C:14]1[N:15]=[N:16][C:17]([CH3:20])=[CH:18][CH:19]=1.[I-].C(N(CC)CC)C>COCCOC>[CH3:20][C:17]1[N:16]=[N:15][C:14]([C:5]#[C:6][C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 30165Iodide IonHCID 2272543-Chloro-6-methylpyridazineHCID 41008573-(Trimethylsilylethynyl)pyridine

Product 1

HCID 116369943-Methyl-6-(pyridin-3-ylethynyl)pyridazine

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To the solution of 3-[(trimethylsilyl)ethynyl]pyridine (0.175g, 1.0 mmol), 3-chloro-6-methylpyridazine (0.128 g, 1.0 mmol), cupper (I) iodide (0.019 g, 0.1 mmol), triethylamine (0.202 g, 2.1 mmol), in 20 ml Ethylene glycol dimethyl ether was added tetrakis(triphenlyphosphine)palladium (0) (60 mg, 0.052 mmol). The result solution was heated to 80° C. after degasing by argon for 5 minute, and then Tetrabutylammonium fluoride (2.1 ml, 1M/THF) was added dropwise. After stirring at 80° C. for 12 hour, the reaction mixture was quenched with H2O (30 mL), then extracted with EtOAc (3×30 mL) and the combined organic extracts washed with brine. The organic phase was dried over Na2SO4 and concentrated in vacuo. The crude purified by liquid chromatography on silica gel using an ISCO single channel system (Hexane/EtOAc: 9/1 to 1/9) to give 3-methyl-6-(pyridin-3-ylethynyl)pyridazine as brown solid. 1H NMR (CDCl3 300 MHz) δ 8.875-8.87 (m, 1H), 8.65-8.63 (d, 1H), 7.95-7.93 (d, 1H), 7.60-7.58 (dd, 1H), 7.39-7.36 (m, 2H), 2.80 (s, 3H). MS (ESI) 196.10 (M++H).

Workup

  1. customafter degasing by argon for 5 minute
  2. additionTetrabutylammonium fluoride (2.1 ml, 1M/THF) was added dropwise
  3. customthe reaction mixture was quenched with H2O (30 mL)
  4. extractionextracted with EtOAc (3×30 mL)
  5. washthe combined organic extracts washed with brine
  6. dry with materialThe organic phase was dried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude purified by liquid chromatography on silica gel using an ISCO single channel system (Hexane/EtOAc: 9/1 to 1/9)

Sources & evidence

ORD record
ord-1a60b7be88ea455d8a619e1d5bb5f441
Source dataset
uspto-grants-2008_04
Patent number
US07365074B2

Linked notes

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