Ethyl Acetoacetate → Ethyl 4-amino-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridine-5-carboxylate

HRID 573546Notes

Reaction equation

HRID 573546 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH3:16])[CH:10]=2)[C:6]=1[C:7]#[N:8].[C:17]([O:23][CH2:24][CH3:25])(=[O:22])[CH2:18][C:19]([CH3:21])=O.Cl[Sn](Cl)(Cl)Cl>C1(C)C=CC=CC=1>[NH2:8][C:7]1[C:18]([C:17]([O:23][CH2:24][CH3:25])=[O:22])=[C:19]([CH3:21])[N:1]=[C:2]2[S:3][CH:4]=[C:5]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH3:16])[CH:10]=3)[C:6]=12

Participants

5

Reactant 3

HCID 8868Ethyl AcetoacetateHCID 24287Tin tetrachlorideHCID 167961562-Amino-4-[3-(methyloxy)phenyl]-3-thiophenecarbonitrile

Product 1

HCID 68323793Ethyl 4-amino-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridine-5-carboxylateYield 61.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 2-amino-4-[3-(methyloxy)phenyl]-3-thiophenecarbonitrile (1 g, 4.34 mmol) (Description 13), ethyl acetoacetate (0.550 mL, 4.34 mmol) and SnCl4 (1.019 mL, 8.68 mmol) in toluene (25 mL) was stirred at RT for 30 min followed by reflux for 3 h. After cooling to RT, the mixture was quenched with 2M NaOH (50 mL) and extracted with ethyl acetate (3×40 mL). The combined organics were washed with brine (50 mL), dried and concentrated. Purification by chromatography on silica gel, eluting with a gradient of 0-50% ethyl acetate in cyclohexane, to give the title compound (915 mg). LCMS (A) m/z: 343 [M+1]+, Rt 1.25 min (acidic).

Workup

  1. temperatureby reflux for 3 h
  2. temperatureAfter cooling to RT
  3. customthe mixture was quenched with 2M NaOH (50 mL)
  4. extractionextracted with ethyl acetate (3×40 mL)
  5. washThe combined organics were washed with brine (50 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-5c4aab08a7ae4938aa1026bbf02f2d4b
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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