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 1760716Notes

Reaction equation

HRID 1760716 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-c2f9a13640904af1821f0568fd0d292e
Source dataset
uspto-grants-2005_01
Patent number
US06844362B2

Reaction notes

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