Triethylamine → 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

HRID 354188Notes

Reaction equation

HRID 354188 reaction equation
I[C:2]1[CH:3]=[C:4]([C:13]2[NH:14][C:15](=[O:26])[C:16]3[C:17](=[C:19]([CH2:23][CH2:24][CH3:25])[N:20]([CH3:22])[N:21]=3)[N:18]=2)[C:5]([O:8][CH2:9][CH:10]([CH3:12])[CH3:11])=[N:6][CH:7]=1.[OH:27][N:28]=[C:29]([NH2:31])[CH3:30].[CH2:32](N(CC)CC)C.[C]=O>C1(C)C=CC=CC=1.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:9]([O:8][C:5]1[C:4]([C:13]2[NH:14][C:15](=[O:26])[C:16]3[C:17](=[C:19]([CH2:23][CH2:24][CH3:25])[N:20]([CH3:22])[N:21]=3)[N:18]=2)=[CH:3][C:2]([C:32]2[O:27][N:28]=[C:29]([CH3:30])[N:31]=2)=[CH:7][N:6]=1)[CH:10]([CH3:12])[CH3:11]

Participants

8

Reactant 4

HCID 8471Triethylamine2×HCID 30926N-Hydroxyacetamidine2×HCID 1357305795-(5-Iodo-2-isobutoxy-3-pyridinyl)-2-methyl-3-propyl-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-oneHCID 178418416HCID 178418416, compound

Product 1

HCID 1357305995-[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-oneYield 39.4%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

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.

Workup

  1. customThe cooled reaction mixture
  2. washwashed with water and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customPurification
  7. washby flash column chromatography (gradient elution from dichloromethane:1% methanol:dichloromethane)

Sources & evidence

ORD record
ord-5a07ce19e6ac40fc8698459315868cac
Source dataset
uspto-grants-2004_06
Patent number
US06756373B1

Reaction notes

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