Ethyl 4-[6-(ethoxycarbonyl)-3-pyridazinyl]-2-(4-fluorobenzyl)-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizine-3-carboxylate → 6-[3-(Ethoxycarbonyl)-2-(4-fluorobenzyl)-5-oxo-7,8,9,9a-tetrahydro-5h-pyrido[2,3-a]pyrrolizin-4-yl]-3-pyridazinecarboxylic acid

HRID 458450Notes

Reaction equation

HRID 458450 reaction equation
C([O:3][C:4]([C:6]1[N:11]=[N:10][C:9]([C:12]2[C:17]3[C:18](=[O:24])[N:19]4[CH:23]([C:16]=3[N:15]=[C:14]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)[C:13]=2[C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:22][CH2:21][CH2:20]4)=[CH:8][CH:7]=1)=[O:5])C>O1CCOCC1.[OH-].[Na+]>[CH2:36]([O:35][C:33]([C:13]1[C:14]([CH2:25][C:26]2[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=2)=[N:15][C:16]2[CH:23]3[N:19]([C:18](=[O:24])[C:17]=2[C:12]=1[C:9]1[N:10]=[N:11][C:6]([C:4]([OH:5])=[O:3])=[CH:7][CH:8]=1)[CH2:20][CH2:21][CH2:22]3)=[O:34])[CH3:37]

Participants

4

Reactant 1

HCID 18442002Ethyl 4-[6-(ethoxycarbonyl)-3-pyridazinyl]-2-(4-fluorobenzyl)-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizine-3-carboxylate

Product 1

HCID 697426146-[3-(Ethoxycarbonyl)-2-(4-fluorobenzyl)-5-oxo-7,8,9,9a-tetrahydro-5h-pyrido[2,3-a]pyrrolizin-4-yl]-3-pyridazinecarboxylic acidYield 90.5%

Reagents, catalysts & solvents 2

HCID 14798Sodium HydroxideSolventHCID 312751,4-DioxaneSolvent

Procedure

To the ethyl 4-[6-(ethoxycarbonyl)-3-pyridazinyl]-2-(4-fluorobenzyl)-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizine-3-carboxylate (F, 145 mg, 0.29 mmol) in 2.5 ml dioxane, 1.2 ml 1N NaOH was added and the resulting mixture was stirred overnight. Acidified with 2N HCl and extracted with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. Removal of the solvent and purification of the resulting residue with flash chromatography afforded 125 mg off-white solid. 1H NMR (400 MHz, CDCl3) δ 8.38 (d, 1H), 8.17 (d, 1H), 7.20 (t, 2H), 6.95 (t, 2H), 4.79 (m, 1H), 4.42 (m, 2H), 3.98 (q, 2H), 3.62 (m, 1H), 3.39 (m, 1H), 2.45 (m, 1H), 2.32 (m, 2H), 1.41 (m, 1H), 0.92 (t, 3H) ppm. ESI-MS m/z 475 (M−H)−.

Workup

  1. extractionAcidified with 2N HCl and extracted with ethyl acetate
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. customRemoval of the solvent and purification of the resulting residue with flash chromatography

Sources & evidence

ORD record
ord-6ee45fb2cab74b419a996759a8959f87
Source dataset
uspto-grants-2007_03
Patent number
US07189851B2

Reaction notes

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