Hydrazine → benzyl 4-(6-oxo-6,7-dihydro-5H-imidazo[4,5-c]pyridazin-5-yl)piperidine-1-carboxylate

HRID 271882

Reaction equation

HRID 271882 reaction equation
[CH2:1]([CH:4]1[N:8]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:16])[CH2:11][CH2:10]2)[C:7](=[O:25])[NH:6][C:5]1=O)[CH:2]=C.I([O-])(=O)(=O)=O.[Na+].[NH2:33][NH2:34]>C1COCC1.O.[O-]S([O-])=O.[Na+].[Na+].C([O-])(O)=O.[Na+].C(O)(=O)C.[Os](=O)(=O)(=O)=O>[O:25]=[C:7]1[NH:6][C:5]2[N:33]=[N:34][CH:2]=[CH:1][C:4]=2[N:8]1[CH:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:16])[CH2:11][CH2:10]1

Participants

10

Reactant 3

HCID 9321HydrazineHCID 22293269Benzyl 4-(5-allyl-2,4-dioxoimidazolidin-1-yl)piperidine-1-carboxylateHCID 23667635Sodium periodate

Product 1

HCID 22293218benzyl 4-(6-oxo-6,7-dihydro-5H-imidazo[4,5-c]pyridazin-5-yl)piperidine-1-carboxylateYield 6.8%

Reagents, catalysts & solvents 6

HCID 30318Osmium TetroxideCatalystHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 24437Sodium SulfiteSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
50 °C

Procedure

Benzyl 4-(5-allyl-2,4-dioxoimidazolidin-1-yl)piperidine-1-carboxylate (0.480 g, 1.34 mmol) was dissolved in THF (5 mL), and osmium tetroxide (0.05 mL, 2.5% solution in t-butanol) was added followed by a solution of sodium periodate (0.862 g, 4.03 mmol) in water (4 mL). After 24 h, the reaction was diluted with saturated aqueous Na2SO3 and NaHCO3 and extracted with ethyl acetate (4×). The combined organic washes were dried over sodium sulfate, filtered and evaporated to give the crude aldehyde (0.352 g). To a portion of this material (0.250 g, 0.696 mmol) in acetic acid (10 mL) was added hydrazine (0.446 mL, 13.9 mmol). This mixture was heated at 50° C. for 24 h, and then concentrated to dryness. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid) gave the product (0.032 g). MS 354.2 (M+1).

Workup

  1. extractionextracted with ethyl acetate (4×)
  2. dry with materialThe combined organic washes were dried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customto give the crude aldehyde (0.352 g)
  6. concentrationconcentrated to dryness
  7. customPurification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-eab4cd7b42634159aae56d7c6cdbfff2
Source dataset
uspto-grants-2008_11
Patent number
US07452903B2

Linked notes

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