Acetic Acid → 1-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid

HRID 1941892Notes

Reaction equation

HRID 1941892 reaction equation
[C:1]1([N:7]2[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:28]=[CH:27][C:24]([CH:25]=O)=[CH:23][CH:22]=4)[N:17]=3)[CH:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O)(=O)C.[NH:33]1[CH2:36][CH:35]([C:37]([OH:39])=[O:38])[CH2:34]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO.ClCCCl>[C:1]1([N:7]2[C:11]([C:12]([F:13])([F:14])[F:15])=[C:10]([C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:22]=[CH:23][C:24]([CH2:25][N:33]5[CH2:36][CH:35]([C:37]([OH:39])=[O:38])[CH2:34]5)=[CH:27][CH:28]=4)[N:17]=3)[CH:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 931923-azetidinecarboxylic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 866590404-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)benzaldehyde

Product 1

HCID 468359231-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acidYield 56%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent

Procedure

To a solution of 4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)benzaldehyde (700 mg, 1.821 mmol) in MeOH (12 mL) and 1,2-dichloroethane (3 mL) was added 0.1 mL of acetic acid and azetidine-3-carboxylic acid (203 mg, 2.0 mmol). The mixture was allowed to stir at room temperature for 40 min. and then sodium triacetoxyborohydride (618 mg, 2.91 mmol) was added. The mixture was allowed to stir at room temperature for 5 hours, then was filtered to afford a white solid that was washed with water (1 mL) and MeOH (3×1 mL). The solid was dried under vacuum to give 1-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid (480 mg, 1.02 mmol). The compound had an HPLC retention time=6.91 min. −Column: Low pH Col-1: Sunfire C18 3.5 um, 4.6×150 mm; Start % B=10; 12 Min. 100%; 15 Min. 100%; Flow Rate=2 mL/min; Wavelength1=220; Wavelength2=254; Solvent Pair=TFA-MeCN/H2O; Solvent A=0.05% TFA in H2O:MeCN (95:5); Solvent B=0.05% TFA in H2O:MeCN (5:95); Column 1=LOW pH-Parallel HPLC; At 220 nm LC/MS M+1=470.1 1H NMR (500 MHz, MeOD) δ ppm 3.41 (dt, J=8.8 Hz, 7.7 Hz, 1H), 4.12-4.18 (m, 4H), 4.38 (s, 2H), 7.57-7.66 (m, 7H), 8.23 (d, J=8.3 Hz, 2H), 8.50 (s, 1H).

Workup

  1. stirringto stir at room temperature for 5 hours
  2. filtrationwas filtered
  3. customto afford a white solid
  4. washthat was washed with water (1 mL) and MeOH (3×1 mL)
  5. customThe solid was dried under vacuum

Sources & evidence

ORD record
ord-7cc21caecbb84640888dabe7f97a2747
Source dataset
uspto-grants-2013_03
Patent number
US08389509B2

Reaction notes

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