(+-)-3-Quinuclidinol → (+/-)-3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid 1-aza-bicyclo[2.2.2]oct-3-yl ester

HRID 2355986Notes

Reaction equation

HRID 2355986 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH2:11][CH:12]([NH:16][C:17]([N:19]2[CH2:24][CH2:23][CH:22]([N:25]3[CH2:34][C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[NH:27][C:26]3=[O:35])[CH2:21][CH2:20]2)=[O:18])[C:13]([OH:15])=[O:14])[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2.CCN=C=NCCCN(C)C.[N:47]12[CH2:54][CH2:53][CH:50]([CH2:51][CH2:52]1)[CH:49](O)[CH2:48]2>CN(C)C1C=CN=CC=1.CN(C)C=O>[N:47]12[CH2:54][CH2:53][CH:50]([CH2:51][CH2:52]1)[CH:49]([O:14][C:13](=[O:15])[CH:12]([NH:16][C:17]([N:19]1[CH2:20][CH2:21][CH:22]([N:25]3[CH2:34][C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[NH:27][C:26]3=[O:35])[CH2:23][CH2:24]1)=[O:18])[CH2:11][C:4]1[CH:5]=[C:6]3[C:10](=[C:2]([CH3:1])[CH:3]=1)[NH:9][N:8]=[CH:7]3)[CH2:48]2

Participants

6

Reactant 3

HCID 15381(+-)-3-QuinuclidinolHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 21102025(+)-3-(7-methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid

Product 1

HCID 11478806(+/-)-3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid 1-aza-bicyclo[2.2.2]oct-3-yl ester

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of (±)-3-(7-methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid (50 mg, 0.105 mmol), EDCI (100 mg), and 4-dimethylaminopyridine (0.2 equiv.) in dimethylformamide was added aza-bicyclo[2.2.2]oct-3-yl alcohol (0.525 mmol, 5 equiv.). The mixture was stirred at room temperature overnight. The solvent was removed in vacuo and the residue was dissolved in ethyl acetate, washed with brine, dried over magnesium sulfate, and purified by preparative HPLC to yield the desired compound. LC/MS: tR=1.62 min, 586.41 (MH)+.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over magnesium sulfate
  5. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-8dd9f424cd37439d9ea8eb3ead68ab2a
Source dataset
uspto-grants-2010_07
Patent number
US07754732B2

Reaction notes

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