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

HRID 573555Notes

Reaction equation

HRID 573555 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH3:9])[C:6]=1[C:7]#[N:8].[C:10]([O:16][CH2:17][CH3:18])(=[O:15])[CH2:11][C:12]([CH3:14])=O.Cl[Sn](Cl)(Cl)Cl>C1(C)C=CC=CC=1>[NH2:8][C:7]1[C:11]([C:10]([O:16][CH2:17][CH3:18])=[O:15])=[C:12]([CH3:14])[N:1]=[C:2]2[S:3][CH:4]=[C:5]([CH3:9])[C:6]=12

Participants

5

Reactant 3

HCID 8868Ethyl AcetoacetateHCID 24287Tin tetrachlorideHCID 2642812-Amino-4-methylthiophene-3-carbonitrile

Product 1

HCID 68323726Ethyl 4-amino-3,6-dimethylthieno[2,3-b]pyridine-5-carboxylateYield 38.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 2-amino-4-methyl-3-thiophenecarbonitrile (300 mg, 2.171 mmol), ethyl acetoacetate (0.275 mL, 2.171 mmol) and SnCl4 (0.510 mL, 434 mmol) in toluene (15 mL) was stirred at RT for 30 min and then reflux for 3.5 h. After cooling to RT, the mixture was quenched with 6M NaOH (20 mL) and extracted with ethyl acetate (3×20 mL). The combined organics were washed with brine (30 mL), dried and concentrated. Purification by chromatography on silica gel, eluting with a gradient of 0-50% ethyl acetate in cyclohexane, afforded the title compound (210 mg). LCMS (A) m/z: 251 [M+1]+, Rt 0.77 min (acidic).

Workup

  1. temperaturereflux for 3.5 h
  2. temperatureAfter cooling to RT
  3. customthe mixture was quenched with 6M NaOH (20 mL)
  4. extractionextracted with ethyl acetate (3×20 mL)
  5. washThe combined organics were washed with brine (30 mL)
  6. customdried
  7. concentrationconcentrated
  8. customPurification by chromatography on silica gel
  9. washeluting with a gradient of 0-50% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-4c4c5f8993c744e5b8256fcc68aa764b
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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