Ammonium formate → HCID 22609936, compound

HRID 2306604Notes

Reaction equation

HRID 2306604 reaction equation
C([O:8][CH:9]1[CH2:12][CH:11]([C:13]2[C:18]([O:19][CH2:20][C:21]3[N:22]([CH3:26])[N:23]=[CH:24][N:25]=3)=[N:17][N:16]3[C:27]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[F:36])=[N:28][N:29]=[C:15]3[CH:14]=2)[CH2:10]1)C1C=CC=CC=1.C([O-])=O.[NH4+]>[Pd].C(O)=O>[F:36][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=1[C:27]1[N:16]2[N:17]=[C:18]([O:19][CH2:20][C:21]3[N:22]([CH3:26])[N:23]=[CH:24][N:25]=3)[C:13]([CH:11]3[CH2:12][CH:9]([OH:8])[CH2:10]3)=[CH:14][C:15]2=[N:29][N:28]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 22609902HCID 22609902, compound

Product 1

HCID 22609936HCID 22609936, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 284Formic AcidSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 7-(3-benzyloxycyclobutyl)-3-(2-fluorophenyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine (0.04 g, 0.082 mmol), excess ammonium formate (1.0 g), formic acid (1 ml) and 10% palladium on carbon (0.10 g) was stirred at 60° C. under nitrogen for 18 h, then cooled and concentrated. The residue was diluted with dichloromethane (20 ml) and washed with brine (20 ml). The organic layer was dried (Na2SO4), filtered and concentrated. Preparative thin layer chromatogaphy on silica gel, eluting with 10% methanol-dichloromethane, gave recovered 7-(3-benzyloxycyclobutyl)-3-(2-fluorophenyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine (0.016 g, 40%) and 3-(2-fluorophenyl)-7-(3-hydroxycyclobutyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine (0.009 g, 28%) as a white solid, a 3:1 mixture of trans:cis isomers; 1H NMR (360 MHz, CDCl3) δ 2.08-2.18, 2.36-2.56 and 2.70-2.84 (4H, m), 3.00-3.08 and 3.70-3.78 (1H, m), 3.82 (3H, s), 4.36-4.40 and 4.44-4.58 (1H, m), 5.47 (2H, s), 7.24-7.32 (1H, m), 7.43-7.40 (1H, m), 7.54-7.60 (1H, m), 7.82-7.96 (3H, m); MS (ES+) m/e 396 [MH]+.

Workup

  1. temperaturecooled
  2. concentrationconcentrated
  3. additionThe residue was diluted with dichloromethane (20 ml)
  4. washwashed with brine (20 ml)
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. washPreparative thin layer chromatogaphy on silica gel, eluting with 10% methanol-dichloromethane
  9. customgave
  10. customrecovered 7-(3-benzyloxycyclobutyl)-3-(2-fluorophenyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine (0.016 g, 40%) and 3-(2-fluorophenyl)-7-(3-hydroxycyclobutyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine (0.009 g, 28%) as a white solid
  11. additiona 3:1 mixture of trans

Sources & evidence

ORD record
ord-9528fe0ab0864904a0e9783b9342ca02
Source dataset
uspto-grants-2004_12
Patent number
US06828322B2

Reaction notes

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