Thionyl Chloride → HCID 21084065, compound

HRID 347928Notes

Reaction equation

HRID 347928 reaction equation
O[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:14](=[O:15])[CH:13]=[CH:12][C:11]3[C:16]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[C:17]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[S:18][C:10]2=3)=[CH:5][CH:4]=1.[H-].[Na+].S(Cl)([Cl:34])=O.C([O-])(O)=O.[Na+]>C1COCC1.CN(C=O)C>[Cl:34][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:14](=[O:15])[CH:13]=[CH:12][C:11]3[C:16]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[C:17]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[S:18][C:10]2=3)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 21084069HCID 21084069, compound

Product 1

HCID 21084065HCID 21084065, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of the compound of Example 88 (130 mg, 0.32 mmol) in THF (2 mL) was added NaH (14 mg of 60% dispersion in oil, 0.35 mmol). DMF (0.5 mL) was added to aid solubility and the reaction was stirred for 1 h. Thionyl chloride (25 μL, 0.35 mmol) was added to the reaction mixture cooled in an ice-bath. The mixture was stirred in the ice-bath for 30 mins before quenching the reaction with water (20 mL) and basifying with NaHCO3(aq). The product was extracted into DCM (2×15 mL) and the combined DCM layers dried over MgSO4, filtered and concentrated in vacuo to give ethyl 7-(4-chloromethylphenyl)-6-oxo-3-phenyl-6,7-dihydrothieno[2,3-b]pyridine-2-carboxylate LCMS (ES+) RT 3.97 minutes, 424 (M+H)+. To a solution of this compound in DMF (1 mL) was added 2-methylimidazole (13 mg, 0.16 mmol) and caesium carbonate (52 mg, 0.16 mmol) and the mixture heated at 80° for 3 h. DMF was removed in vacuo and the residue purified by column chromatography (silica, 40–100% EtOAc in isohexane followed by 5% MeOH in DCM) and also mass directed hpic to give the title compound as a solid (3 mg). δH (MeOH-d4) 7.47–7.27 (10 H, m), 7.06 (1H, d, J 1.4 Hz), 6.82 (1H, d, J 1.4 Hz), 6.50 (1H, d, J 9.6 Hz), 5.26 (2H, s), 4.00 (2H, q, J 7.1 Hz), 2.28 (3H, s), 0.99 (3H, t, J 7.1 Hz). LCMS (ES+) RT 2.53 minutes, 470 (M+H)+.

Workup

  1. temperaturecooled in an ice-bath
  2. custombefore quenching
  3. customthe reaction with water (20 mL)
  4. extractionThe product was extracted into DCM (2×15 mL)
  5. dry with materialthe combined DCM layers dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5ac935180a1f49aa8cf0b704150765f6
Source dataset
uspto-grants-2007_02
Patent number
US07176215B2

Reaction notes

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