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

HRID 889594Notes

Reaction equation

HRID 889594 reaction equation
[S-:1][C:2]#[N:3].[K+].Br[C:6]1[N:11]=[CH:10][C:9]([NH2:12])=[CH:8][CH:7]=1.BrBr.[C:15](O)(=[O:17])C>>[CH3:15][O:17][C:6]1[N:11]=[C:10]2[S:1][C:2]([NH2:3])=[N:12][C:9]2=[CH:8][CH:7]=1

Participants

5

Reactant 4

HCID 176Acetic Acid3×HCID 24408BromineHCID 516872Potassium thiocyanateHCID 6428116-Bromopyridin-3-amine

Product 1

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

Conditions

Temperature
0 °C

Procedure

Potassium thiocyanate (156 g, 1600 mmol) is dissolved in acetic acid (1400 mL) and cooled to 0° C. 6-Bromo-pyridin-3-ylamine (50 g, 400 mmol) is dissolved in acetic acid (100 mL) and added dropwise over 10 min. Bromine (25 mL, 480 mmol) is dissolved in acetic acid (100 mL) and added dropwise over 10 min. The reaction is allowed to stir and warm to RT overnight. Acetic acid is removed via concentration. The resulting residue is poured into water (1 L) and adjusted to pH=7 with 1 N sodium hydroxide solution. This is extracted with ethyl acetate. Extracts are combined, washed with brine, and concentrated to a brown sludge. Recrystallization from methanol affords 5-methoxy-thiazolo[5,4-b]pyridin-2-ylamine as a brown solid: 1H NMR (400 MHz, DMSO-D6) δ 3.8 (s, 3 H) 6.7 (d, J=8.8 Hz, 1 H) 7.4 (s, 2 H) 7.6 (d, J=8.6 Hz, 1 H); LC/MS 182.3 (M+1), 180.4 (M−1).

Workup

  1. additionadded dropwise over 10 min
  2. additionadded dropwise over 10 min
  3. temperaturewarm to RT overnight
  4. customAcetic acid is removed via concentration
  5. additionThe resulting residue is poured into water (1 L)
  6. extractionThis is extracted with ethyl acetate
  7. washwashed with brine
  8. concentrationconcentrated to a brown sludge
  9. customRecrystallization from methanol

Sources & evidence

ORD record
ord-00c7a6b6d1f1426ab0f42da518a0ec19
Source dataset
uspto-grants-2012_08
Patent number
US08252931B2

Reaction notes

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