Azetidine → HCID 136150027, compound

HRID 2263405Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:31]=[CH:32][C:33]=1[C:34]1[NH:38][C:37](=[O:39])[O:36][N:35]=1)[O:6][CH2:7][C:8]1[S:12][C:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)=[N:10][C:9]=1[CH2:23][CH2:24][CH2:25]OS(C)(=O)=O.[NH:40]1[CH2:43][CH2:42][CH2:41]1.C(N(C(C)C)CC)(C)C>C(#N)C>[N:40]1([CH2:25][CH2:24][CH2:23][C:9]2[N:10]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:20])([F:21])[F:22])=[CH:15][CH:14]=3)[S:12][C:8]=2[CH2:7][O:6][C:5]2[CH:31]=[CH:32][C:33]([C:34]3[NH:38][C:37](=[O:39])[O:36][N:35]=3)=[C:3]([O:2][CH3:1])[CH:4]=2)[CH2:43][CH2:42][CH2:41]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a suspension of 130 mg of methanesulfonic acid 3-[5-[3-methoxy-4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-phenoxymethyl]-2-(4-trifluoromethyl-phenyl)-thiazol-4-yl]-propyl ester in 7 mL of acetonitrile was added 25 μL of azetidine and 57 mg of diisopropylethyl amine. The resulting mixture was heated in a sealed tube to 60° C. under microwave irradiation for 30 minutes and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (gradient from dichloromethane 100 to dichloromethane 90/methanol 10/water 1/acetic acid 1) followed by a 2 g SCX Waters column with gradient CH2Cl2/MeOH 30/70 to 7N NH3 in MeOH and another column chromatography on silica gel (eluting with dichloromethane 90/methanol 10) to give 3.5 mg of 3-{4-[4-(3-azetidin-1-yl-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-phenyl}-4H-[1,2,4]oxadiazol-5-one.

Workup

concentrationconcentrated under reduced pressure
customThe residue was purified by column chromatography on silica gel (gradient from dichloromethane 100 to dichloromethane 90/methanol 10/water 1/acetic acid 1)

Sources & evidence

ORD record: ord-a04a363e2f4447db8477a701ae04c781
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07851493B2

Reaction notes

Loading…