(+-)-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 2250298Notes

Reaction equation

HRID 2250298 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-5b8e240562364e13a78d06db82b0a317
Source dataset
uspto-grants-2008_01
Patent number
US07314883B2

Reaction notes

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