3-Chloro-6-hydrazinopyridazine → (S)-1-(6-chloro[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethanol

HRID 912057Notes

Reaction equation

HRID 912057 reaction equation
[Cl:1][C:2]1[N:3]=[N:4][C:5]([NH:8][NH2:9])=[CH:6][CH:7]=1.[OH:10][C@@H:11]([CH3:15])[C:12](O)=O.CC1C=CC(S(O)(=O)=O)=CC=1.O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]2[N:4]([C:12]([C@@H:11]([OH:10])[CH3:15])=[N:9][N:8]=2)[N:3]=1

Participants

5

Reactant 3

HCID 1007873-Chloro-6-hydrazinopyridazineHCID 107689L-Lactic AcidHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 57812716(S)-1-(6-chloro[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethanol

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 3-chloro-6-hydrazinopyridazine (1.44 g, 9.96 mmol), (S)-2-hydroxypropanoic acid (1.06 g, 10 mmol, i.e. L-lactic acid, 85% in water) and p-TsOH.H2O (2.37 g, 12.4 mmol) in toluene was refluxed overnight. Some oil formed at the bottom of the flask. LC-MS of this oil showed the desired product was formed. Toluene was poured off, and the oil residue was suspended in water (10 mL), then basified with 3 N aq. NaOH to pH=10. This aqueous solution was extracted with EtOAc (3×30 mL), and the combined organic phases were washed with brine (20 mL), and dried over anhydrous sodium sulfate. Evaporation under reduced pressure afforded the title compound as an off-white solid. MS (ES+): 199/201 (3/1) [MH+]. 1H NMR (400 MHz, CDCl3): δ=1.88 (d, J=6.8 Hz, 3H), 2.94 (d, J=6.6 Hz, 1H, —OH), 5.51 (m, 1H), 7.15 (d, J=9.6 Hz, 1H), 8.11 (d, J=9.6 Hz, 1H).

Workup

  1. temperaturewas refluxed overnight
  2. customSome oil formed at the bottom of the flask

Sources & evidence

ORD record
ord-2279ee2058a44116a2bab4843e5fba18
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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