Hydrazine hydrate (1:1) → 4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)-5,6,7-trimethyl-2,6-dihydro-1H-pyrrolo[3,4-d]pyridazin-1-one

HRID 1091744Notes

Reaction equation

HRID 1091744 reaction equation
O.[NH2:2][NH2:3].[F:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([C:14]2[C:15]([C:22]([O:24]C)=O)=[C:16]([CH3:21])[N:17]([CH3:20])[C:18]=2[CH3:19])=O)=[CH:7][C:6]=1[C:26]([N:28]1[CH2:33][CH2:32][CH:31]([O:34][CH3:35])[CH2:30][CH2:29]1)=[O:27]>C(O)(=O)C>[F:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[C:14]3[C:15](=[C:16]([CH3:21])[N:17]([CH3:20])[C:18]=3[CH3:19])[C:22](=[O:24])[NH:2][N:3]=2)=[CH:7][C:6]=1[C:26]([N:28]1[CH2:33][CH2:32][CH:31]([O:34][CH3:35])[CH2:30][CH2:29]1)=[O:27]

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 57791825Methyl 4-(2-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)phenyl)acetyl)-1,2,5-trimethyl-1H-pyrrole-3-carboxylate

Product 1

HCID 577918584-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)-5,6,7-trimethyl-2,6-dihydro-1H-pyrrolo[3,4-d]pyridazin-1-oneYield 5.5%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Hydrazine hydrate (0.014 mL, 0.19 mmol) was added to methyl 4-(2-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)phenyl)acetyl)-1,2,5-trimethyl-1H-pyrrole-3-carboxylate (59) (0.076 g, 0.17 mmol) in acetic acid (4 mL). The resulting solution was stirred at room temperature for 2 days. The resulting mixture was evaporated to dryness and the residue was azeotroped with toluene to afford crude product, which was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the desired compound (4.00 mg, 5.49% yield); m/z (LC-MS, ESI+), RT=1.60 min (M+H=427.11).

Workup

  1. customThe resulting mixture was evaporated to dryness
  2. customthe residue was azeotroped with toluene
  3. customto afford crude product, which
  4. customwas purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  5. additionFractions containing the desired compound
  6. customwere evaporated to dryness

Sources & evidence

ORD record
ord-4d99762481d94fb68db470e87873f9af
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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