2-Ethyl-7-hydroxymethyl-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one → 2-ethyl-5-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidine-7-carbaldehyde
Reaction equation
[CH2:1]([C:3]1[S:14][C:6]2=[N:7][C:8]([CH2:12][OH:13])=[CH:9][C:10](=[O:11])[N:5]2[N:4]=1)[CH3:2]>CC(C)=O.O=[Mn]=O>[CH2:1]([C:3]1[S:14][C:6]2=[N:7][C:8]([CH:12]=[O:13])=[CH:9][C:10](=[O:11])[N:5]2[N:4]=1)[CH3:2]Participants
Procedure
A mixture of 7-Chloromethyl-2-ethyl-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one (11.48 g, 50 mmol), sodium iodide (15 g, 100 mmol, 2 equiv), sodium bicarbonate (12.6 g, 150 mmol, 3 equiv), water (25 mL) and DMSO (250 mL) was stirred and heated at 80° C. for 18 h. The volatiles were mostly removed on the rotary evaporator, then the residue treated with ethyl acetate to precipitate the salts, and the mixture filtered. The filtrate was lyophilized and chromatographed on silica gel using a gradient of ethyl acetate to 3% methanol in ethyl acetate, affording 2-ethyl-7-hydroxymethyl-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one (4.24 g, 40%). This alcohol was dissolved in acetone (150 mL) and refluxed for 3 days with a total of 15 equivalents of MnO2, added in 3-equiv portions over this time, affording complete conversion to the corresponding aldehyde. The reaction mixture was filtered through celite, the cake washed with acetone (3×100 mL), and the filtrate concentrated in vacuo, affording the title product (2.84 g, 67%). 1H NMR (300 MHz, CDCl3): δ 1.55 (t, 3H), 3.10 (q, 2H), 6.98 (s, 1H), 9.90 (s, 1H). MS (APCI) calcd for C8H7ClN3O2S: 209.03, found (M+H+): 210.2.
Workup
- additionadded in 3-equiv portions over this time
Sources & evidence
- ORD record
- ord-bec0cc0d6f8641c78a66fd7ef2a8a6b9
- Source dataset
- uspto-grants-2006_12
- Patent number
- US07151105B2
Reaction notes
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