Methyl Thioglycolate → 3-Amino-2-carbomethoxythieno[3,2-b]pyridine-4-oxide

HRID 235067Notes

Reaction equation

HRID 235067 reaction equation
Cl[C:2]1[C:3]([C:9]#[N:10])=[N+:4]([O-:8])[CH:5]=[CH:6][CH:7]=1.[C:11]([O:15][CH3:16])(=[O:14])[CH2:12][SH:13].C[O-].[Na+]>CN(C=O)C>[NH2:10][C:9]1[C:3]2=[N+:4]([O-:8])[CH:5]=[CH:6][CH:7]=[C:2]2[S:13][C:12]=1[C:11]([O:15][CH3:16])=[O:14]

Participants

5

Reactant 3

HCID 16907Methyl ThioglycolateHCID 10942334Sodium MethoxideHCID 187969753-chloro-2-cyanopyridine-N-oxide

Product 1

HCID 104893153-Amino-2-carbomethoxythieno[3,2-b]pyridine-4-oxideYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-chloro-2-cyanopyridine (40g, 0.29 mol) in 500 mL acetic acid added hydrogen peroxide (30%, 52 g, 0.45 mol) dropwise. After stirring at 90° C. for 18 h, the reaction is cooled to 25° C. and a solution of sodium sulfite (57 g, 0.45 mol) in H2O is added dropwise. The reaction is concentrated to remove the bulk of the acetic acid and the residue is partitioned between 1M NaOH and CH2Cl2. The CH2Cl2 layer is dried (MgSO4), filtered, concentrated, and recrystallized from EtOAc to provide 23 g (51%) of 3-chloro-2-cyanopyridine-N-oxide. The N-oxide from above (12.2 g, 79 mmol) was taken up in DMF (160 mL) at 0° C. Methyl thioglycolate (7.1 mL, 79 mmol) was added followed by sodium methoxide (8.5 g, 160 mmol) in portions. The RXN was stirred for 1 h. The RXN was poured onto ice and the resulting solid was collected by filtration, washed with water, dissolved in CH2Cl2, dried (MgSO4), filtered, concentrated, and recrystallized from EtOAc. 10.6 g (60%) of 3-amino-2-carbomethoxythieno[3,2-b]pyridine-4-oxide was obtained. The pyridine-N-oxide (10.6 g, 47 mmol) is mixed with phosphorous oxychloride (100 mL). The RXN is heated to 80° C. for 30 min. The RXN is concentrated and partitioned between CH2Cl2 and NaHCO3 sln. The CH2Cl2 layer is dried (MgSO4), filtered, cone, and chromatographed (5:1 hex:EtOAc). 8.3g (73%) of the 5-chloro and 2.0 g (18%) of the 7-chloro product were obtained: 1H NMR (300 MHz, CDCl3 (5-chloro)) δ3.92 (s, 3H), 6.15 (bs, 2H), 7.37 (d, 1H), 7.99 (d, 1H); MS (DCI/NH3) m/e 243 (M+H)+. 1H NMR (300 MHz, CDCl3 (7-chloro)) δ3.93 (s, 3H), 6.20 (bs, 2H), 7.41 (d, 1H), 8.54 (db, 1H); MS (DCI/NH3) m/e 243 (M+H)+.

Workup

  1. filtrationthe resulting solid was collected by filtration
  2. washwashed with water
  3. dissolutiondissolved in CH2Cl2
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customrecrystallized from EtOAc

Sources & evidence

ORD record
ord-a7b6f89c6563426991c80acc9b7a5bb9
Source dataset
uspto-grants-1997_01
Patent number
US05597823

Reaction notes

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