Ethyl Acetoacetate → Ethyl 4-amino-6-methylthieno[2,3-b]pyridine-5-carboxylate

HRID 573584Notes

Reaction equation

HRID 573584 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[CH:5][C:6]=1[C:7]#[N:8].[C:9]([O:15][CH2:16][CH3:17])(=[O:14])[CH2:10][C:11]([CH3:13])=O.Cl[Sn](Cl)(Cl)Cl>C1(C)C=CC=CC=1>[NH2:8][C:7]1[C:10]([C:9]([O:15][CH2:16][CH3:17])=[O:14])=[C:11]([CH3:13])[N:1]=[C:2]2[S:3][CH:4]=[CH:5][C:6]=12

Participants

5

Reactant 3

HCID 8868Ethyl AcetoacetateHCID 24287Tin tetrachlorideHCID 7366072-Aminothiophene-3-carbonitrile

Product 1

HCID 68323805Ethyl 4-amino-6-methylthieno[2,3-b]pyridine-5-carboxylateYield 25.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 2-amino-3-thiophenecarbonitrile (2 g, 16.11 mmol), ethyl acetoacetate (2.24 mL, 17.72 mmol) and SnCl4 (3.78 mL, 32.2 mmol) in toluene (120 mL) was stirred at RT for 30 min and then at reflux for ca. 4 h. After cooling to RT, the mixture was quenched with 6M NaOH (ca. 80 mL), diluted with ethyl acetate (80 mL) and then filtered through celite. The organic layer of the filtrate was separated and the aqueous layer was re-extracted with ethyl acetate (50 mL×5). The combined organics were dried and concentrated. Purification by chromatography on silica, eluting with a gradient of 0-50% ethyl acetate in cyclohexane, to give the title compound (960 mg). LCMS (A) m/z: 237 [M+1]+, Rt 0.67 min (acidic).

Workup

  1. temperatureat reflux for ca. 4 h
  2. temperatureAfter cooling to RT
  3. customthe mixture was quenched with 6M NaOH (ca. 80 mL)
  4. additiondiluted with ethyl acetate (80 mL)
  5. filtrationfiltered through celite
  6. customThe organic layer of the filtrate was separated
  7. extractionthe aqueous layer was re-extracted with ethyl acetate (50 mL×5)
  8. customThe combined organics were dried
  9. concentrationconcentrated
  10. customPurification by chromatography on silica
  11. washeluting with a gradient of 0-50% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-5d11a0b2c5084ab591fb66a22b7da0ad
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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