Hydrochloric Acid → 5-Methyl-3-(2-{3-[2-(trifluoromethyl)phenoxy]pyrrolidin-1-yl}-1,3-thiazol-5-yl)-1,2,4-oxadiazole

HRID 2355063Notes

Reaction equation

[OH:1][N:2]=[C:3]([C:5]1[S:9][C:8]([N:10]2[CH2:14][CH2:13][CH:12]([O:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]([F:25])([F:24])[F:23])[CH2:11]2)=[N:7][CH:6]=1)[NH2:4].[C:26](OC(=O)C)(=O)[CH3:27].Cl>N1C=CC=CC=1.O>[CH3:26][C:27]1[O:1][N:2]=[C:3]([C:5]2[S:9][C:8]([N:10]3[CH2:14][CH2:13][CH:12]([O:15][C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[C:22]([F:25])([F:24])[F:23])[CH2:11]3)=[N:7][CH:6]=2)[N:4]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To N′-hydroxy-2-{3-[2-(trifluoromethyl)phenoxy]pyrrolidin-1-yl}-1,3-thiazole-5-carboximidamide (190 mg, 0.51 mmol) in pyridine (1.5 mL) at rt was added acetic anhydride (48 μL, 0.51 mmol) and heated at 100° C. for 4 h. After cooling, the reaction mixture was diluted with water, acidified with 1 N HCl (20 mL) and extracted with EtOAc. The EtOAc layer was washed with diluted brine, dried (Na2SO4) and concentrated. Combi-Flash chromatography (10 g, 50-100% EtOAc in hexanes in 20 min, 20 mL/min, 15 mL/fraction) gave a white solid which was triturated with Et2O to give the title compound as a white powder. 1H NMR (400 MHz, acetone-d6): δ 7.81 (s, 1 H), 7.71-7.65 (m, 2 H), 7.41 (d, 1 H), 7.17 (t, 1 H), 5.52 (s, 1 H), 3.98 (m, 1 H), 3.84-3.67 (m, 3 H), 2.61 (s, 3 H), 2.60-2.43 (m, 2 H). MS (+ESI) m/z 397 (MH+).

Workup

temperatureAfter cooling
extractionextracted with EtOAc
washThe EtOAc layer was washed with diluted brine
dry with materialdried (Na2SO4)
concentrationconcentrated
customCombi-Flash chromatography (10 g, 50-100% EtOAc in hexanes in 20 min, 20 mL/min, 15 mL/fraction) gave a white solid which
customwas triturated with Et2O

Sources & evidence

ORD record: ord-3ca15d33e44c4fdaa0a80d98cbbfecf7
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07754745B2

Reaction notes

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