Water → 2-Ethyl-7-hydroxymethyl-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one

HRID 2387104Notes

Reaction equation

HRID 2387104 reaction equation
Cl[CH2:2][C:3]1[N:4]=[C:5]2[S:12][C:11]([CH2:13][CH3:14])=[N:10][N:6]2[C:7](=[O:9])[CH:8]=1.[I-].[Na+].C(=O)(O)[O-:18].[Na+].O>CS(C)=O>[CH2:13]([C:11]1[S:12][C:5]2=[N:4][C:3]([CH2:2][OH:18])=[CH:8][C:7](=[O:9])[N:6]2[N:10]=1)[CH3:14]

Participants

6

Reactant 4

HCID 962WaterHCID 5238Sodium IodideHCID 516892Sodium BicarbonateHCID 71308367-(chloromethyl)-2-ethyl-5H-(1,3,4)thiadiazolo(3,2-a)pyrimidin-5-one

Product 1

HCID 167698582-Ethyl-7-hydroxymethyl-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-oneYield 40.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

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

  1. customThe volatiles were mostly removed on the rotary evaporator
  2. additionthe residue treated with ethyl acetate
  3. customto precipitate the salts
  4. filtrationthe mixture filtered
  5. customchromatographed on silica gel using a gradient of ethyl acetate to 3% methanol in ethyl acetate

Sources & evidence

ORD record
ord-b4464e64451045cb83bbbfb47d3d192e
Source dataset
uspto-grants-2012_09
Patent number
US08268835B2

Reaction notes

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