Hydrogen Bromide → 7-Methoxy-4-morpholin-4-yl-thiazolo[5,4-c]pyridin-2-ylamine

HRID 917410Notes

Reaction equation

HRID 917410 reaction equation
[CH3:1][O:2][C:3]1[C:4]([NH:15][C:16]([NH2:18])=[S:17])=[CH:5][C:6]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[N:7][CH:8]=1.Br.CS(C)=O>C(OCC)(=O)C>[CH3:1][O:2][C:3]1[C:4]2[N:15]=[C:16]([NH2:18])[S:17][C:5]=2[C:6]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[N:7][CH:8]=1

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 679Dimethyl SulfoxideHCID 58962702(5-Methoxy-2-morpholin-4-yl-pyridin-4-yl)-thiourea

Product 1

HCID 860385537-Methoxy-4-morpholin-4-yl-thiazolo[5,4-c]pyridin-2-ylamineYield 64%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred suspension of 3.51 g (13.1 mmol) (5-methoxy-2-morpholin-4-yl-pyridin-4-yl)-thiourea in 75 ml ethyl acetate heated to reflux was added dropwise over 5 min 4.59 ml (26.2 mmol) hydrobromic acid (5.7 M solution in acetic acid) and stirring continued for a further 15 min. 1.12 ml (15.7 mmol) DMSO was then added dropwise and the reaction mixture stirred for a further 30 min at reflux. The mixture was then cooled to room temperature and partitioned between tetrahydrofuran and saturated brine. 5 N sodium hydroxide solution was added until the aqueous phase was pH 14, then 10% aq. citric acid solution was added until the aqueous phase was pH 6. The mixture was stirred for 20 min and then the phases were separated. The organic phase was dried over sodium sulfate and concentrated in vacuo. Trituration of the residue in ether afforded 2.23 g (64%) 7-methoxy-4-morpholin-4-yl-thiazolo[5,4-c]pyridin-2-ylamine as an off-white crystalline solid. ES-MS m/e (%): 267 (M+H+, 100).

Workup

  1. temperatureheated
  2. temperatureto reflux
  3. stirringthe reaction mixture stirred for a further 30 min
  4. temperatureat reflux
  5. custompartitioned between tetrahydrofuran and saturated brine
  6. addition5 N sodium hydroxide solution was added until the aqueous phase
  7. addition10% aq. citric acid solution was added until the aqueous phase
  8. stirringThe mixture was stirred for 20 min
  9. customthe phases were separated
  10. dry with materialThe organic phase was dried over sodium sulfate
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-94b3c28f9a834a67ba45925ebbbdb35d
Source dataset
uspto-grants-2007_09
Patent number
US07273865B2

Reaction notes

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