Hydrochloric Acid → 7-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-(5-formylthien-3-yl)thieno[3,2-b]pyridine-6-carbonitrile

HRID 1178665Notes

Reaction equation

HRID 1178665 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[NH:11][C:12]1[C:17]([C:18]#[N:19])=[CH:16][N:15]=[C:14]2[CH:20]=[C:21]([C:23]3[CH:27]=[C:26]([CH:28]4OCC[O:29]4)[S:25][CH:24]=3)[S:22][C:13]=12.Cl.C(=O)(O)[O-].[Na+]>O1CCCC1>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[NH:11][C:12]1[C:17]([C:18]#[N:19])=[CH:16][N:15]=[C:14]2[CH:20]=[C:21]([C:23]3[CH:27]=[C:26]([CH:28]=[O:29])[S:25][CH:24]=3)[S:22][C:13]=12

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 222566327-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-[5-(1,3-dioxolan-2-yl)thien-3-yl]thieno[3,2-b]pyridine-6-carbonitrile

Product 1

HCID 103442217-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-(5-formylthien-3-yl)thieno[3,2-b]pyridine-6-carbonitrileYield 87.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To the suspension of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-[5-(1,3-dioxolan-2-yl)thien-3-yl]thieno[3,2-b]pyridine-6-carbonitrile (337 mg, 0.67 mmol) in 10 mL of tetrahydrofuran is added 5 mL of 2N hydrochloric acid. The mixture is stirred at room temperature, overnight. The mixture is slowly poured into 30 mL of saturated aqueous sodium bicarbonate and extracted with chloroform. The organic layer is washed with saturated aqueous sodium chloride, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with 5% methanol in dichloromethane to provide 271 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-(5-formylthien-3-yl)thieno[3,2-b]pyridine-6-carbonitrile as yellow crystals, mp 259–261° C.; 1H NMR (DMSO-d6) δ 3.85 (s, 3H), 7.38 (s, 1H), 7.76 (s, 1H), 7.93 (s, 1H), 8.42 (s, 1H), 8.50 (s, 1H), 8.63 (s, 1H), 9.76 (s, 1H), 9.98 (s, 1H); MS 458.1 (M−H)−.

Workup

  1. extractionextracted with chloroform
  2. washThe organic layer is washed with saturated aqueous sodium chloride
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by flash column chromatography
  7. washeluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-53c3e2cd35ba4597a5c654eff7217a2a
Source dataset
uspto-grants-2007_10
Patent number
US07276519B2

Reaction notes

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