Water → 5-Methoxy[1,3]thiazolo[5,4-b]pyridin-2-amine

HRID 1009022Notes

Reaction equation

HRID 1009022 reaction equation
[S-:1][C:2]#[N:3].[K+].[NH2:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][CH3:13])=[N:10][CH:11]=1.BrBr.O>C(O)(=O)C>[CH3:13][O:12][C:9]1[N:10]=[C:11]2[S:1][C:2]([NH2:3])=[N:5][C:6]2=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24408BromineHCID 811216-Methoxy-3-pyridinylamineHCID 516872Potassium thiocyanate

Product 1

HCID 28015575-Methoxy[1,3]thiazolo[5,4-b]pyridin-2-amine

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Conditions

Temperature
0 °C

Procedure

Potassium thiocyanate Fluka 60519 (38.8 g, 400 mmol, 8.0 equiv.) and 5-amino-2-methoxypyridine Aldrich A6, 120-9 (6.2 g, 50 mmol, 1.0 equiv.) were added to 100 mL glacial acetic acid precooled to 5° C. (semi solid) with mechanical stirring. Bromine (23.9 g, 150 mmol, 3.0 equiv.) dissolved in 30 mL glacial acetic acid was added dropwise to the reaction mixture over 1.5 hr at 0° C. The thick slurry was stirred 2 hrs at 0° C. and overnight at RT. Then 30 mL water was added to the orange suspension, which was heated to 85° C. and filtered hot. The residue was treated again with acetic acid, heated and filtered like before. The combined filtrates were cooled and neutralized with NH4OH at pH 6. The red precipitate was filtered, dissolved in ethyl acetate and washed with NaHCO3 and brine, dried over Na2SO4, evaporated and crystallized from ethyl acetate-hexane using charcoal to give 5-methoxy-thiazolo[5,4-b]pyridin-2-ylamine m/e 182.0 (MH+).

Workup

  1. customprecooled to 5° C.
  2. additionwas added dropwise to the reaction mixture over 1.5 hr at 0° C
  3. temperaturewas heated to 85° C.
  4. filtrationfiltered hot
  5. additionThe residue was treated again with acetic acid
  6. temperatureheated
  7. filtrationfiltered like before
  8. temperatureThe combined filtrates were cooled
  9. filtrationThe red precipitate was filtered
  10. dissolutiondissolved in ethyl acetate
  11. washwashed with NaHCO3 and brine
  12. dry with materialdried over Na2SO4
  13. customevaporated
  14. customcrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-cfbd7db98fb8452dac13b9e687db8f0c
Source dataset
uspto-grants-2011_07
Patent number
US07973051B2

Reaction notes

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