Methyl iodide → 4-Chloro-2-methylthieno[2,3-b]pyridine-5-carbonitrile

HRID 1178614

Reaction equation

HRID 1178614 reaction equation
[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]2[S:10][CH:11]=[CH:12][C:3]=12.[CH:13]([N-]C(C)C)(C)C.[Li+].CCCCCCC.O1CCCC1.C(C1C=CC=CC=1)C.IC>O1CCCC1.O.ClCCl>[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]2[S:10][C:11]([CH3:13])=[CH:12][C:3]=12

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 114129074-Chlorothieno[2,3-b]pyridine-5-carbonitrileHCID 22742125Tetrahydrofuran heptane ethylbenzol

Product 1

HCID 222566394-Chloro-2-methylthieno[2,3-b]pyridine-5-carbonitrile

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-chlorothieno[2,3-b]pyridine-5-carbonitrile (0.3 g, 1.54 mmol) in 15 mL of tetrahydrofuran at −78° C. is added dropwise 2.0 M lithium diisopropylamide in heptane/tetrahydrofuran/ethylbenzene (0.93 mL, 1.85 mmol). After stirring for 45 min, a solution of iodomethane (0.115 mL, 1.85 mmol) in 1 mL of tetrahydrofuran is added dropwise. The reaction mixture is stirred at −78° C. for 4 hours, then dichloromethane and water are added. The mixture is allowed to warm to room temperature, then partitioned between water and dichloromethane. The organic layer is washed with a solution of sodium thiosulfate, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with 1:9 ethyl acetate:hexane to provide 0.1 g of 4-chloro-2-methylthieno[2,3-b]pyridine-5-carbonitrile as colorless crystals, mp 101–102° C.; 1H NMR (DMSO-d6) δ 2.68 (s, 3H), 7.39 (s, 1H), 8.92 (s, 1H); MS 209.0 (M+H)+.

Workup

  1. stirringThe reaction mixture is stirred at −78° C. for 4 hours
  2. custompartitioned between water and dichloromethane
  3. washThe organic layer is washed with a solution of sodium thiosulfate
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by flash column chromatography
  8. washeluting with 1:9 ethyl acetate

Sources & evidence

ORD record
ord-e098f85ec59d4135bfa1973b4d843e01
Source dataset
uspto-grants-2007_10
Patent number
US07276519B2

Linked notes

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