(Diethylamino)sulfur trifluoride → 5,6,7,8 tetrahydro-2-[2,4-dichloro-5-(2-propynyloxy)phenyl]-6-fluoro-1,2,4-triazolo[4,3-alpha]pyridin-3(2H)-one

HRID 1964

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH2:10][C:11]#[CH:12])=[CH:4][C:3]=1[N:13]1[C:22](=[O:23])[N:16]2[CH2:17][CH:18](O)[CH2:19][CH2:20][C:15]2=[N:14]1.C(N(S(F)(F)[F:30])CC)C>ClCCl>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH2:10][C:11]#[CH:12])=[CH:4][C:3]=1[N:13]1[C:22](=[O:23])[N:16]2[CH2:17][CH:18]([F:30])[CH2:19][CH2:20][C:15]2=[N:14]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 169 mg (0.477 mmol) of 5,6,7,8-tetrahydro-2-[2,4-dichloro-5-(2-propynyloxy)phenyl]-6-hydroxy-1,2,4-triazolo[4,3-a]pyridin-3(2H)-one in 5 mL of dichloromethane was added 76 μl (0.573 mmol) of diethylaminosulfur trifluoride (DAST) at 0° C. The reaction mixture was stirred at 0° C. for 1h. The mixture was then quenched with ice and extracted with dichloromethane. The organic extracts were dried (MgSO4), and then concentrated in vacuo to give a pale red solid. The crude product was purified by flash chromatography over silica gel, eluting with a 95:5 v:v mixture of dichloromethane and methanol to give 64 mg of the title product as a pale yellow foam. 19F NMR (CDCl3, 400 MHz) δ-188 ppm, 1H NMR (CDCl3, 400 MHz) δ 7.5 (s,1H), 7.1 (s,1H), 5.2 (m,1H), 4.8 (s,2H), 4.2-3.6 (m,2H), 3.2-3.0 (m,1H), 3.0-2.6 (m,1H), 2.5 (s,1H), 2.3-1.8 (m,2H).

Workup

customThe mixture was then quenched with ice
extractionextracted with dichloromethane
dry with materialThe organic extracts were dried (MgSO4)
concentrationconcentrated in vacuo
customto give a pale red solid
customThe crude product was purified by flash chromatography over silica gel
washeluting with a 95:5 v
additionv mixture of dichloromethane and methanol

Sources & evidence

ORD record: ord-9634d1d63f934be6bfca6b1b336ece9e
Source dataset: uspto-grants-1998_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05728651

Linked notes

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