Ethyl 2-((pyridin-3-yl)methoxy)acetate → 3-(((pyridin-3-yl)methoxy)methyl)-N-(3-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-amine

HRID 446905Notes

Reaction equation

HRID 446905 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][O:8][CH2:9][C:10](OCC)=O)[CH:2]=1.[Cl:15][C:16]1[CH:17]=[C:18]([NH:22][C:23]2[N:24]=[N:25][C:26]([NH:29][NH2:30])=[CH:27][CH:28]=2)[CH:19]=[CH:20][CH:21]=1>CS(C)=O.Cl.CO>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][O:8][CH2:9][C:10]2[N:25]3[N:24]=[C:23]([NH:22][C:18]4[CH:19]=[CH:20][CH:21]=[C:16]([Cl:15])[CH:17]=4)[CH:28]=[CH:27][C:26]3=[N:29][N:30]=2)[CH:2]=1

Participants

5

Reactant 2

HCID 19261392Ethyl 2-((pyridin-3-yl)methoxy)acetateHCID 59363292N-(3-chlorophenyl)-6-hydrazinylpyridazin-3-amine

Product 1

HCID 248307123-(((pyridin-3-yl)methoxy)methyl)-N-(3-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-amine

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 21893726Hydrochloride methanolSolvent

Procedure

(Step 4-ii) Ethyl 2-((pyridin-3-yl)methoxy)acetate (65 mg, 0.33 mmol) and N-(3-chlorophenyl)-6-hydrazinylpyridazin-3-amine (60 mg, 0.25 mmol) were combined in a 16×100 mm test tube and placed into a 160° C. oil bath for 15 min. The residue was dissolved in 1 mL DMSO and purified by reversed-phase HPLC. Fractions containing pure product were concentrated in vacuo to yield a solid, dissolved in HCl/methanol, and concentrated in vacuo to give the yellow solid product, 3-(((pyridin-3-yl)methoxy)methyl)-N-(3-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-amine, as an HCl salt (22 mg, 0.055 mmol, 22% yield). 1H-NMR (500 MHz, DMSO-d6) 10.25 (s, 1H), 8.80 (s, 1H), 8.77 (d, J=5.2 Hz, 1H), 8.40 (d, J=8.1 Hz, 1H), 8.16 (d, J=9.9 Hz, 1H), 8.07 (t, J=2.0 Hz, 1H), 7.90 (dd, J=5.6, 7.9 Hz, 1H), 7.61 (dd, J=2.0, 8.2 Hz, 1H), 7.36 (t, J=8.1 Hz, 1H), 7.20 (d, J=9.9 Hz, 1H), 7.08-7.06 (m, 1H), 5.11 (s, 2H), 4.89 (s, 2H); MH+367.3.

Workup

  1. customplaced into a 160° C.
  2. customfor 15 min
  3. custompurified by reversed-phase HPLC
  4. additionFractions containing pure product
  5. concentrationwere concentrated in vacuo
  6. customto yield a solid
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-65a4b79f0f2c45d8885e836512a9eea4
Source dataset
uspto-grants-2013_07
Patent number
US08481538B2

Reaction notes

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