Diethyl 2-[(2S)-1-(tert-butoxycarbonyl)pyrrolidinyl]-4-[6-(ethoxycarbonyl)-3-pyridazinyl]-6-(4-fluorobenzyl)-3,5-pyridinedicarboxylate → Ethyl 4-[6-(ethoxycarbonyl)-3-pyridazinyl]-2-(4-fluorobenzyl)-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizine-3-carboxylate

HRID 458449Notes

Reaction equation

HRID 458449 reaction equation
C([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]1[C:18](C(OCC)=O)=[C:17]([C:24]2[N:25]=[N:26][C:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:28][CH:29]=2)[C:16]([C:35]([O:37][CH2:38][CH3:39])=[O:36])=[C:15]([CH2:40][C:41]2[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=2)[N:14]=1)=O)(C)(C)C>FC(F)(F)C(O)=O.ClCCl>[CH2:33]([O:32][C:30]([C:27]1[N:26]=[N:25][C:24]([C:17]2[C:18]3[C:6](=[O:5])[N:8]4[CH:9]([C:13]=3[N:14]=[C:15]([CH2:40][C:41]3[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=3)[C:16]=2[C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:10][CH2:11][CH2:12]4)=[CH:29][CH:28]=1)=[O:31])[CH3:34]

Participants

4

Reactant 1

HCID 69516647Diethyl 2-[(2S)-1-(tert-butoxycarbonyl)pyrrolidinyl]-4-[6-(ethoxycarbonyl)-3-pyridazinyl]-6-(4-fluorobenzyl)-3,5-pyridinedicarboxylate

Product 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-carboxylateYield 71.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

Diethyl 2-[(2S)-1-(tert-butoxycarbonyl)pyrrolidinyl]-4-[6-(ethoxycarbonyl)-3-pyridazinyl]-6-(4-fluorobenzyl)-3,5-pyridinedicarboxylate (E, 260 mg crude) was first dissolved in 15 ml mixture of trifluoroacetic acid and dichloromethane (2 to 1 ratio) and stirred for 1 hour followed by the removal of the solvent. To this residue, 15 ml of mixture of triethylamine and dichloromethane (1 to 2 ratio) was added and the mixture was stirred for 2 hours. Upon removal of the solvent, the residue was purified by flash chromatography. 145 mg solid was obtained. 1H NMR (400 MHz, CDCl3) δ 8.21 (d, 1H), 8.03 (d, 1H), 7.18 (t, 2H), 6.90 (t, 2H), 4.75 (m, 1H), 4.54 (q, 2H), 4.42 (m, 2H), 3.96 (q, 2H), 3.65 (m, 1H), 3.38 (m, 1H), 2.45 (m, 1H), 2.32 (m, 2H), 1.45 (t, 3H), 1.40 (m, 1H), 0.92 (t, 3H) ppm. ESI-MS m/z 505 (M+H)+.

Workup

  1. customfollowed by the removal of the solvent
  2. additionTo this residue, 15 ml of mixture of triethylamine and dichloromethane (1 to 2 ratio) was added
  3. stirringthe mixture was stirred for 2 hours
  4. customUpon removal of the solvent
  5. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-0a7c54b8b5c94756964b7e7dc6adc2b8
Source dataset
uspto-grants-2007_03
Patent number
US07189851B2

Reaction notes

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