Water → 6-Chloro-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazole

HRID 69561Notes

Reaction equation

C(OC([N:8]=[C:9]1[N:13]([CH2:14][C:15](O)=O)[N:12]=[C:11]([CH2:18][O:19][CH3:20])[S:10]1)=O)(C)(C)C.C(N(CC)CC)C.P(Cl)(Cl)([Cl:30])=O.O>C(#N)C>[Cl:30][C:15]1[N:8]=[C:9]2[N:13]([CH:14]=1)[N:12]=[C:11]([CH2:18][O:19][CH3:20])[S:10]2

Participants

Conditions

Temperature: 80 °C

Procedure

To {2-[(tert-butoxycarbonyl)imino]-5-(methoxymethyl)-1,3,4-thiadiazol-3(2H)-yl}acetic acid a33 (418 g, 1.378 mol, 1 eq) in acetonitrile (2.51) at room temperature, are successively and slowly added triethyl amine (278.9 g, 2.756 mol, 2 eq), then phosphorous oxychloride (633.9 g, 4.134 mol, 3 eq). The reaction mixture is heated at 80° C. for one hour. After reaction completion, water (2.2 l) is slowly and carefully added at 50° C. The reaction mixture is extracted with dichloromethane (2×1.21), the combined organic layers are washed by a NaOH/NaCl aqueous solution (1.4 l of saturated NaCl solution+400 ml 2N NaOH), dried over MgSO4, filtered and condensed under reduced pressure. The residue is recrystallized from acetonitrile/water (1/1) to afford 99.8 g of pure 6-chloro-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazole a35.

Workup

customat room temperature
additioncarefully added at 50° C
extractionThe reaction mixture is extracted with dichloromethane (2×1.21)
washthe combined organic layers are washed by a NaOH/NaCl aqueous solution (1.4 l of saturated NaCl solution+400 ml 2N NaOH)
dry with materialdried over MgSO4
filtrationfiltered
customcondensed under reduced pressure
customThe residue is recrystallized from acetonitrile/water (1/1)

Sources & evidence

ORD record: ord-64df23a1c7804d298af637772a1d5a90
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822508B2

Reaction notes

Loading…