Methyl iodide → 7-Chloro-2-methylthieno[3,2-b]pyridine-6-carbonitrile

HRID 1178615Notes

Reaction equation

HRID 1178615 reaction equation
[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]2[CH:10]=[CH:11][S:12][C:3]=12.[CH:13]([N-]C(C)C)(C)C.[Li+].CCCCCCC.O1CCCC1.C(C1C=CC=CC=1)C.IC>O1CCCC1>[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]2[CH:10]=[C:11]([CH3:13])[S:12][C:3]=12

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 118164017-Chlorothieno[3,2-b]pyridine-6-carbonitrileHCID 22742125Tetrahydrofuran heptane ethylbenzol

Product 1

HCID 222566287-Chloro-2-methylthieno[3,2-b]pyridine-6-carbonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7-chlorothieno[3,2-b]pyridine-6-carbonitrile (500 mg, 2.57 mmol) in 15 mL of tetrahydrofuran at −78° C. is added dropwise 2.0 M lithium diisopropylamide in heptane/tetrahydrofuran/ethylbenzene (1.6 mL, 3.21 mmol). After stirring for 40 minutes, iodomethane (616 mg, 0.27 mL, 4.34 mmol) is added dropwise over 7 minutes. The reaction mixture is stirred at −78° C. for 5 hours, then the mixture is partitioned between 20 mL of dichloromethane and 10 mL of water. The organic layer is washed with a saturated aqueous ammonium chloride solution, followed by saturated aqueous sodium chloride, then dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with a gradient of 5% ethyl acetate in hexane to 20% ethyl acetate in hexane to provide 274 mg of 7-chloro-2-methylthieno[3,2-b]pyridine-6-carbonitrile as a white solid, mp 163–164° C.; 1H NMR (DMSO-d6) δ 2.73 (s, 3H), 7.55 (s, 1H), 9.03 (s, 1H); MS 209.0, 211.1 (M+H)+.

Workup

  1. stirringThe reaction mixture is stirred at −78° C. for 5 hours
  2. customthe mixture is partitioned between 20 mL of dichloromethane and 10 mL of water
  3. washThe organic layer is washed with a saturated aqueous ammonium chloride solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by flash column chromatography
  8. washeluting with a gradient of 5% ethyl acetate in hexane to 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-eca04e4c4f8c4f9f9de297c9dacde5cf
Source dataset
uspto-grants-2007_10
Patent number
US07276519B2

Reaction notes

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