1-[4-(2-(Azepan-1-yl)ethoxy)benzyl]-5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-3-methyl-1H-indole → Bazedoxifene

HRID 1862562Notes

Reaction equation

HRID 1862562 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][N:28]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)=[CH:21][CH:20]=1)[C:13]([C:35]1[CH:40]=[CH:39][C:38]([O:41]CC3C=CC=CC=3)=[CH:37][CH:36]=1)=[C:12]2[CH3:49])C1C=CC=CC=1>C1COCC1.CCO>[N:28]1([CH2:27][CH2:26][O:25][C:22]2[CH:21]=[CH:20][C:19]([CH2:18][N:14]3[C:15]4[C:11](=[CH:10][C:9]([OH:8])=[CH:17][CH:16]=4)[C:12]([CH3:49])=[C:13]3[C:35]3[CH:36]=[CH:37][C:38]([OH:41])=[CH:39][CH:40]=3)=[CH:24][CH:23]=2)[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1

Participants

3

Reactant 1

HCID 98958311-[4-(2-(Azepan-1-yl)ethoxy)benzyl]-5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-3-methyl-1H-indole

Product 1

HCID 154257Bazedoxifene

Reagents, catalysts & solvents 1

HCID 21873804Tetrahydrofuran ethanolSolvent

Procedure

A solution consisting of indole 44 (17.5g, 26.9 mmol) in THF/EtOH (1:1) was hydrogenated under an atmosphere of H2 using 10% Pd/C as a catalyst. Chromatography on silica gel CH2Cl2/MeOH (gradient from 100/0 to 85/15) yields the desired product as 8.5 g of white foam along with 2.5 g of a fraction containing small impurities. Although the free base is the material used in the next step (bis-glucuronidation), for purposes of characterization and enhancing the compounds shelf life an acid addition salt may be made with HCl by dissolving the compound in MeOH and treating with 1.1 eq of a 2 N aq HCl solution. The compound slowly precipitates out as white crystals. Physical data listed below describes the HCl salt of indole 45:

Sources & evidence

ORD record
ord-fa4dfd38c6944c3ca10afd6a3617661b
Source dataset
uspto-grants-2003_03
Patent number
US06537971B2

Reaction notes

Loading…