HCID 58505549, compound → HCID 178471307, compound

HRID 1917600Notes

Reaction equation

HRID 1917600 reaction equation
C([O:8][C:9]1[CH:10]=[CH:11][N:12]2[C:16]([CH:17]=1)=[C:15]([C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:14]([CH2:24][C:25]([CH3:32])([CH3:31])[C:26]([O:28][CH2:29][CH3:30])=[O:27])=[C:13]2[C:33]([C:35]1[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=1)=[O:34])C1C=CC=CC=1>CCO.[Pd]>[Cl:41][C:38]1[CH:37]=[CH:36][C:35]([C:33]([C:13]2[N:12]3[C:16]([CH:17]=[C:9]([OH:8])[CH:10]=[CH:11]3)=[C:15]([C:18](=[O:23])[C:19]([CH3:21])([CH3:22])[CH3:20])[C:14]=2[CH2:24][C:25]([CH3:31])([CH3:32])[C:26]([O:28][CH2:29][CH3:30])=[O:27])=[O:34])=[CH:40][CH:39]=1

Participants

4

Reactant 1

HCID 58505549HCID 58505549, compound

Product 1

HCID 178471307HCID 178471307, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a stirred solution of ethyl 3-[7-(benzyloxy)-3-[(4-chlorophenyl)carbonyl]-1-(2,2-dimethylpropanoyl)indolizin-2-yl]-2,2-dimethylpropanoate (3.50 g, 6.10 mmol) in EtOH (50 mL) is added 10% Pd/C (480 mg). The suspension is stirred under an atmosphere of hydrogen for 1.5 h then filtered through a pad of diatomaceous earth and washed with EtOH. The filtrate is concentrated in vacuo to give ethyl 3-{3-[(4-chlorophenyl)carbonyl]-1-(2,2-dimethylpropanoyl)-7-hydroxyindolizin-2-yl}-2,2-dimethylpropanoate (2.50 g, 85%). Also obtained is ethyl 3-[1-(2,2-dimethylpropanoyl)-7-hydroxy-3-(phenylcarbonyl)indolizin-2-yl]-2,2-dimethylpropanoate (0.28 g, 10%). A suspension of ethyl 3-{3-[(4-chlorophenyl)carbonyl]-1-(2,2-dimethylpropanoyl)-7-hydroxyindolizin-2-yl}-2,2-dimethylpropanoate (100 mg, 0.207 mmol), 2-(chloromethyl)quinoline-HCl (66.0 mg, 0.310 mmol), and potassium carbonate (114 mg, 0.826 mmol) in DMF (3 mL) is stirred for 24 h at 23° C. The mixture is filtered and concentrated in vacuo to give ethyl 3-{3-[(4-chlorophenyl)carbonyl]-1-(2,2-dimethylpropanoyl)-7-(quinolin-2-ylmethoxy)indolizin-2-yl}-2,2-dimethylpropanoate that is dissolved in THF (2 mL), MeOH (3 mL), and 6M aqueous NaOH (2 mL) and heated at 70° C. for 1 h then cooled to 23° C. and acidified to pH=1 with concentrated aqueous HCl. The mixture is partitioned between CH2Cl2 and brine then organics are dried with MgSO4, filtered, and concentrated in vacuo. Purification of the crude by HPLC (25 to 75% CH3CN/0.1% TFA in water) gives the title compound (60 mg, 49%).

Workup

  1. filtrationthen filtered through a pad of diatomaceous earth
  2. washwashed with EtOH
  3. concentrationThe filtrate is concentrated in vacuo

Sources & evidence

ORD record
ord-fa691808fcdd4106ba956c66d3e14667
Source dataset
uspto-grants-2013_12
Patent number
US08618300B2

Reaction notes

Loading…