Reaction #441370

Reaction equation

5-(5-Iodo-2-isobutoxy-3-pyridinyl)-2-methyl-3-propyl-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

triethylamine

carbon monoxide

N′-hydroxyethanimidamide

acetamidoxime

triethylamine

→

product

Yield 39.4%

5-[2-Isobutoxy-5-(3-methyl-1,2,4-oxadiazol-5-yl)-3-pyridinyl]-2-methyl-3-propyl-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

Yield 39.4%

Solvents

toluene

ethyl acetate

Conditions

Workup

1. 1
   OtherThe cooled reaction mixture
2. 2
   Washwashed with water and brine
3. 3
   Dryingdried (MgSO4)
4. 4
   Filtrationfiltered
5. 5
   Otherevaporated
6. 6
   OtherPurification
7. 7
   Washby flash column chromatography (gradient elution from dichloromethane:1% methanol:dichloromethane)

Procedure

5-(5-Iodo-2-isobutoxy-3-pyridinyl)-2-methyl-3-propyl-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (Example 22) (200 mg, 0.42 mmol) and N′-hydroxyethanimidamide (EP 795 328) (95 mg, 1.28 mmol) were suspended in toluene (4 mL) and triethylamine (86 mg, 0.85 mmol) was added. Pd(PPh3)2Cl2 (15 mg, 0.02 mmol) was added and placed in a preheated oil bath at 95° C. under 1 atmosphere carbon monoxide. After 4 h a further portion of acetamidoxime (50 mg), triethylamine (43 mg) and Pd(PPh3)2Cl2 (15 mg) were added and stirring was continued at 95° C. for 14 h. The cooled reaction mixture was diluted with ethyl acetate and washed with water and brine, dried (MgSO4), filtered and evaporated. Purification by flash column chromatography (gradient elution from dichloromethane:1% methanol:dichloromethane) gave 70 mg product.

Source