Formaldehyde → HCID 57929979, compound

HRID 1930004Notes

Reaction equation

HRID 1930004 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:13]([C:14]2[CH:15]=[CH:16][C:17]3[N:18]([C:20]([CH:23]([CH3:25])[CH3:24])=[N:21][N:22]=3)[N:19]=2)=[CH:12][N:11]([CH:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[N:10]=1.C=O.[C:34](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:13]([C:14]2[CH:15]=[CH:16][C:17]3[N:18]([C:20]([CH:23]([CH3:24])[CH3:25])=[N:21][N:22]=3)[N:19]=2)=[CH:12][N:11]([CH:26]2[CH2:31][CH2:30][N:29]([CH3:34])[CH2:28][CH2:27]2)[N:10]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 57929875HCID 57929875, compound

Product 1

HCID 57929979HCID 57929979, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

The 6-(3-(2,4-difluorophenyl)-1-(piperidin-4-yl)-1H-pyrazol-4-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine (0.10 g, 0.24 mmol; Example #Q.2.1) was suspended in DCE (5 mL) and then formaldehyde (30% solution in water, 0.12 g, 1.18 mmol) and sodium triacetoxyborohydride (0.10 g, 0.47 mmol) were added. After about 1 h, the mixture was concentrated under reduced pressure, dissolved in DMF/HOAc, and purified by RP-HPLC (Table 1, Method d). The appropriate fractions were combined and concentrated under reduced pressure and then the mixture was basified with 2 N NaOH and extracted with EtOAc. The organic solution was dried over MgSO4, filtered, and concentrated under reduced pressure. Evaporation several times with Et2O/heptane gave a white solid which was collected by filtration and dried under vacuum to give the title compound (0.042 g, 41%): LC/MS (Table 1, Method a) Rt=1.83 min; MS m/z: 438.2 (M+H)+.

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. dissolutiondissolved in DMF/HOAc
  3. custompurified by RP-HPLC (Table 1, Method d)
  4. concentrationconcentrated under reduced pressure
  5. extractionextracted with EtOAc
  6. dry with materialThe organic solution was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customEvaporation several times with Et2O/heptane
  10. customgave a white solid which
  11. filtrationwas collected by filtration
  12. customdried under vacuum

Sources & evidence

ORD record
ord-904929c4a01c407f981470f01534a270
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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