Diisopropylcarbodiimide → (2S)-[3-(3-Pyridyl)-1-propyl]-1-[(1,5-dimethylpyrazol-3-yl)carbonyl]azetidine-2-carboxylate

HRID 1264478Notes

Reaction equation

HRID 1264478 reaction equation
[NH:1]1[CH2:4][CH2:3][CH:2]1[C:5]([OH:7])=[O:6].[N:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][CH2:15][CH2:16]O)[CH:9]=1.C(N=[C:22]=[N:23][CH:24]([CH3:26])[CH3:25])(C)C.[C:27]12(CS(O)(=O)=O)C(C)(C)C(CC1)C[C:28]2=[O:29].C[N:43](C1C=CC=CN=1)C>ClCCl>[N:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][CH2:15][CH2:16][O:6][C:5]([C@@H:2]2[CH2:3][CH2:4][N:1]2[C:28]([C:27]2[CH:26]=[C:24]([CH3:25])[N:23]([CH3:22])[N:43]=2)=[O:29])=[O:7])[CH:9]=1

Participants

7

Reactant 5

HCID 12734DiisopropylcarbodiimideHCID 17288Azetidinecarboxylic AcidHCID 178613-PyridinepropanolHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 218852-Dimethylaminopyridine

Product 1

HCID 9884459(2S)-[3-(3-Pyridyl)-1-propyl]-1-[(1,5-dimethylpyrazol-3-yl)carbonyl]azetidine-2-carboxylateYield 279.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(2S)-1-(1,5-dimethylpyrazol-3-yl)carbonyl]azetidine-2-carboxylic acid (129.6 mg, 0.58 mmol, 1.0 eq) was dissolved in dry dichloromethane (10 mL), to which was added 3-(3-pyridyl)-1 -propanol (80 μL, 0.62 mmol, 1.07 eq), diisopropylcarbodiimide (140 μL, 0.89 mmol, 1.53 eq), camphorsulfonic acid (46.3 mg, 0.2 mmol, 0.34 eq) and dimethylaminopyridine (29.2 mg, 0.24 mmol, 0.48 eq) in that order. The mixture was stirred at about room temperature for about 15 hours under argon. The solid was filtered off and washed with dichloromethane. The organic filtrate was concentrated and the residue was subjected to flash chromatography (1-10% methanol in chloroform) to give 191.6 mg (96% yield) of the product as a colorless oil. 1H NMR (CDCl3) δ 1.78-2.82 (series of m and s, 9H); 3.61-3.82 (series of s, 3H); 3.82-4.74 (series of m, 4H); 4.89 and 5.32 (dd, 1H, J=10.3, 6.0, J=10.3, 6.0); 6.50-6.57 (series of s, 1H); 7.18-7.24 (m, 1H); 7.40 and 7.54 (d, 1H, J=7.7, J=7.7); 8.28-8.49 (series of nd, 2H).

Workup

  1. filtrationThe solid was filtered off
  2. washwashed with dichloromethane
  3. concentrationThe organic filtrate was concentrated

Sources & evidence

ORD record
ord-4eb6ce82e4334372be1f271749aaccc2
Source dataset
uspto-grants-2003_04
Patent number
US06544976B1

Reaction notes

Loading…