Formaldehyde → N,3-dimethyl-N-(1-phenylethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-amine

HRID 521557Notes

Reaction equation

HRID 521557 reaction equation
[CH3:1][C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH3:13])[CH:9]=[CH:10][C:5]2=[N:4][N:3]=1.C=O.[BH4-].[Na+].[C:24](O)(C(F)(F)F)=O.[OH-].[Na+]>C1COCC1>[CH3:24][N:11]([CH:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:13])[C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([CH3:1])=[N:3][N:4]=2)[N:7]=1

Participants

7

Reactant 5

HCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 426540463-Methyl-N-(1-phenylethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-amine

Product 1

HCID 71115947N,3-dimethyl-N-(1-phenylethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-Methyl-N-(1-phenylethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-amine (100 mg, 0.395 mmol), paraformaldehyde (119 mg, 3.95 mmol), NaBH4 (74.7 mg, 1.974 mmol) and anhydrous THF (5 mL) were charged into a disposable reaction tube equipped with a stirbar and a septum. TFA (2.5 mL) was slowly added at room temperature over 1 h and the reaction was stirred for an additional 18 h at room temperature. A 1M aqueous solution of NaOH was added until pH˜12 and the product was extracted with CH2Cl2/MeOH (19:1) (4×25 mL). The organic layers were combined, dried over Na2SO4 and concentrated to dryness. The crude product was then diluted with MeOH/H2O (19:1), filtered, purified by preparative HPLC (reverse phase) and lyophilized to give the N,3-dimethyl-N-(1-phenylethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-amine (Compound 2) as a white solid (6 mg; 6% yield). 1H NMR (400 MHz, DMSO-d6): δ 7.98 (d, J=10.1 Hz, 1H), 7.22-7.39 (m, 6H), 5.68 (q, J=6.9 Hz, 1H), 2.81 (s, 3H), 2.52 (s, 3H), 1.56 (d, J=7.1 Hz, 3H). LRMS [M+H]+: 268 m/z.

Workup

  1. customequipped with a stirbar
  2. extractionthe product was extracted with CH2Cl2/MeOH (19:1) (4×25 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to dryness
  5. additionThe crude product was then diluted with MeOH/H2O (19:1)
  6. filtrationfiltered
  7. custompurified by preparative HPLC (reverse phase)

Sources & evidence

ORD record
ord-925e845304b94415976a1f1ef75314ee
Source dataset
uspto-grants-2016_05
Patent number
US09328117B2

Reaction notes

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