Diphenyl Ether → 2-Bromo-6-methyl-3-(3-methylphenyl)thieno[2,3-b]pyridin-4-amine

HRID 573578Notes

Reaction equation

HRID 573578 reaction equation
[NH2:1][C:2]1[C:7](C(OCC)=O)=[C:6]([CH3:13])[N:5]=[C:4]2[S:14][C:15]([Br:24])=[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[CH:18]=3)[C:3]=12.[OH-].[Na+].C1(OC2C=CC=CC=2)C=CC=CC=1>C(O)C>[Br:24][C:15]1[S:14][C:4]2[N:5]=[C:6]([CH3:13])[CH:7]=[C:2]([NH2:1])[C:3]=2[C:16]=1[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[CH:18]=1

Participants

5

Reactant 3

HCID 7583Diphenyl EtherHCID 14798Sodium HydroxideHCID 68324026Ethyl 4-amino-2-bromo-6-methyl-3-(3-methylphenyl)thieno[2,3-b]pyridine-5-carboxylate

Product 1

HCID 683240302-Bromo-6-methyl-3-(3-methylphenyl)thieno[2,3-b]pyridin-4-amineYield 65.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of ethyl 4-amino-2-bromo-6-methyl-3-(3-methyl phenyl)thieno[2,3-b]pyridine-5-carboxylate (Description 58) (900 mg, 2.221 mmol) in ethanol (20 mL) at RT was added aqueous NaOH (5M) (1.0 mL, 5.0 mmol). The reaction mixture was heated to 90° C. for ca. 2 h. After cooling to RT the solvent was removed in vacuo. The residue was re-dissolved in water (ca. 80 mL) and neutralized to ca. pH 7 using aqueous HCl (5M). The solution was then extracted with 20% MeOH in DCM (ca. 50 mL×2). The combined organic layer was passed through a phase separator and the solvent removed in vacuo to give a residue which was subsequently re-dissolved in diphenyl ether (10 mL, 62.9 mmol) and heated to 200° C. for ca. 3 h. The reaction mixture was cooled to RT, passed through an SCX cartridge (eluting with MeOH/2M NH3 MeOH). The basic fractions were combined and the solvent removed in vacuo, to give the title compound (487 mg). LCMS (A) m/z: 333/335 [M+1]+, Rt 0.86 min (acidic).

Workup

  1. temperatureAfter cooling to RT the solvent
  2. customwas removed in vacuo
  3. dissolutionThe residue was re-dissolved in water (ca. 80 mL)
  4. extractionThe solution was then extracted with 20% MeOH in DCM (ca. 50 mL×2)
  5. customthe solvent removed in vacuo
  6. customto give a residue which
  7. temperatureheated to 200° C. for ca. 3 h
  8. temperatureThe reaction mixture was cooled to RT
  9. washpassed through an SCX cartridge (eluting with MeOH/2M NH3 MeOH)
  10. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-b187111dec8541a8a0ac8ff881ad13c5
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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