methyl 5-[(2R)-2-aminopropyl]-1H-indole-2-carboxylate → methyl 5-{(2R)-2-[((2R)-2-[4-(benzyloxy)-3-(hydroxymethyl)phenyl]-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)amino]propyl}-1H-indole-2-carboxylate

HRID 722772Notes

Reaction equation

HRID 722772 reaction equation
[NH2:1][C@H:2]([CH3:17])[CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8]([C:13]([O:15][CH3:16])=[O:14])=[CH:7]2.[CH2:18]([O:25][C:26]1[CH:31]=[CH:30][C:29]([C@@H:32]([O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37])[CH2:33]Br)=[CH:28][C:27]=1[CH2:43][OH:44])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>ClCCl>[NH3:1].[CH2:18]([O:25][C:26]1[CH:31]=[CH:30][C:29]([C@@H:32]([O:35][Si:36]([C:39]([CH3:41])([CH3:40])[CH3:42])([CH3:37])[CH3:38])[CH2:33][NH:1][C@H:2]([CH3:17])[CH2:3][C:4]2[CH:5]=[C:6]3[C:10](=[CH:11][CH:12]=2)[NH:9][C:8]([C:13]([O:15][CH3:16])=[O:14])=[CH:7]3)=[CH:28][C:27]=1[CH2:43][OH:44])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

5

Reactant 2

HCID 12988833methyl 5-[(2R)-2-aminopropyl]-1H-indole-2-carboxylateHCID 12988834[2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methanol

Product 2

HCID 222AmmoniaHCID 12988832methyl 5-{(2R)-2-[((2R)-2-[4-(benzyloxy)-3-(hydroxymethyl)phenyl]-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)amino]propyl}-1H-indole-2-carboxylateYield 60.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of methyl 5-[(2R)-2-aminopropyl]-1H-indole-2-carboxylate (Preparation 14, 5.00 g, 21.5 mmol) and [2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl] oxy}ethyl)phenyl]methanol (Preparation 20, 4.86 g, 10.8 mmol) in dichloromethane (50 ml) was heated to 90° C. allowing the dichloromethane to evaporate gradually. The resulting melt was left at 90° C. for 16 h under nitrogen. The reaction mixture was then cooled to room temperature and the resulting solid triturated with dichloromethane. The solid was filtered off and the solvent removed in vacuo to give a pale orange oil. The residue was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:0.88 ammonia (99:1:0.1 by volume) to give the title compound as a pale yellow oil (3.90 g).

Workup

  1. customto evaporate gradually
  2. customthe resulting solid triturated with dichloromethane
  3. filtrationThe solid was filtered off
  4. customthe solvent removed in vacuo
  5. customto give a pale orange oil
  6. customThe residue was purified by flash column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-8d7e2f8f1110428ca1b5435a9d166d43
Source dataset
uspto-grants-2006_11
Patent number
US07138527B2

Reaction notes

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