Trimethylsilylacetylene → 5-(2-Butoxy-5-trimethylsilylethynyl-3-pyridinyl)-2-[2-(dimethylamino)-ethyl]-3-ethyl-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

HRID 1007148Notes

Reaction equation

HRID 1007148 reaction equation
[CH3:1][Si:2]([C:5]#[CH:6])([CH3:4])[CH3:3].[CH2:7]([O:11][C:12]1[C:17]([C:18]2[NH:19][C:20](=[O:34])[C:21]3[C:22](=[C:24]([CH2:32][CH3:33])[N:25]([CH2:27][CH2:28][N:29]([CH3:31])[CH3:30])[N:26]=3)[N:23]=2)=[CH:16][C:15](I)=[CH:14][N:13]=1)[CH2:8][CH2:9][CH3:10]>C(N(CC)CC)C.C(#N)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>[CH2:7]([O:11][C:12]1[C:17]([C:18]2[NH:19][C:20](=[O:34])[C:21]3[C:22](=[C:24]([CH2:32][CH3:33])[N:25]([CH2:27][CH2:28][N:29]([CH3:30])[CH3:31])[N:26]=3)[N:23]=2)=[CH:16][C:15]([C:6]#[C:5][Si:2]([CH3:4])([CH3:3])[CH3:1])=[CH:14][N:13]=1)[CH2:8][CH2:9][CH3:10]

Participants

6

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 1356742275-(2-butoxy-5-iodo-3-pyridinyl)-2-[2-(dimethylamino)ethyl]-3-ethyl-2,6-dihydro-7H-pyrazolo[4,3-d]-pyrimidin-7-one

Product 1

HCID 1356742305-(2-Butoxy-5-trimethylsilylethynyl-3-pyridinyl)-2-[2-(dimethylamino)-ethyl]-3-ethyl-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-oneYield 93.2%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

Pd(PPh3)2Cl2 (11.2 mg, 0.016 mmol), trimethylsilylacetylene (179 μl, 1.29 mmol) and cuprous iodide (3 mg, 0.016 mmol) were added to a stirred slurry of 5-(2-butoxy-5-iodo-3-pyridinyl)-2-[2-(dimethylamino)ethyl]-3-ethyl-2,6-dihydro-7H-pyrazolo[4,3-d]-pyrimidin-7-one (Example 44 in Annex 1, PCT Application, IB 00/01430) (330 mg, 0.647 mmol) in triethylamine (8 ml) and acetonitrile (2 ml) at room temperature under a nitrogen atmosphere. The mixture was heated at 60° C. for 3 h, cooled and extracted from brine with dichloromethane (2×100 ml). The organics were dried (MgSO4), filtered and concentrated to give a yellow solid. Purification by flash column chromatography (elution with DCM/MeOH, 95:5) gave the title compound as a pale brown oil (290 mg, 93%).

Workup

  1. temperaturecooled
  2. extractionextracted from brine with dichloromethane (2×100 ml)
  3. dry with materialThe organics were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a yellow solid
  7. customPurification
  8. washby flash column chromatography (elution with DCM/MeOH, 95:5)

Sources & evidence

ORD record
ord-1e658c5f85bc498f9196b3513e9d3c84
Source dataset
uspto-grants-2004_09
Patent number
US06794387B2

Reaction notes

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