(-)-2-Butanol → 3-Ethyl-5-[5-(4-ethylpiperazin-1-ylsulphonyl)-2-(1(r)-methyl-n-propoxy)pyridin-3-yl]-2-methyl-2,6-dihydro-7h-pyrazolo[4,3-d]pyrimidin-7-one

HRID 990237

Reaction equation

HRID 990237 reaction equation
C(O[C:4]1[C:9]([C:10]2[NH:11][C:12](=[O:22])[C:13]3[C:14](=[C:16]([CH2:20][CH3:21])[N:17]([CH3:19])[N:18]=3)[N:15]=2)=[CH:8][C:7]([S:23]([N:26]2[CH2:31][CH2:30][N:29]([CH2:32][CH3:33])[CH2:28][CH2:27]2)(=[O:25])=[O:24])=[CH:6][N:5]=1)C.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:44][C@@H:45]([OH:48])[CH2:46][CH3:47]>>[CH2:20]([C:16]1[N:17]([CH3:19])[N:18]=[C:13]2[C:12](=[O:22])[NH:11][C:10]([C:9]3[C:4]([O:48][C@H:45]([CH3:44])[CH2:46][CH3:47])=[N:5][CH:6]=[C:7]([S:23]([N:26]4[CH2:27][CH2:28][N:29]([CH2:32][CH3:33])[CH2:30][CH2:31]4)(=[O:25])=[O:24])[CH:8]=3)=[N:15][C:14]=12)[CH3:21]

Participants

4

Reactant 3

HCID 84682(-)-2-ButanolHCID 3251421Potassium bis(trimethylsilyl)amideHCID 1358163675-[2-Ethoxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridin-3-yl]-3-ethyl-2-methyl-2,6-dihydro-7h-pyrazolo[4,3-d]pyrimidin-7-one

Product 1

HCID 1360364593-Ethyl-5-[5-(4-ethylpiperazin-1-ylsulphonyl)-2-(1(r)-methyl-n-propoxy)pyridin-3-yl]-2-methyl-2,6-dihydro-7h-pyrazolo[4,3-d]pyrimidin-7-oneYield 17%

Conditions

Temperature
110 °C

Procedure

The title compound of Example 78 (400 mg, 0.84 mmol) was added to a mixture of potassium bis(trimethylsilyl)amide (840 mg, 4.2 mmol) in (R)-2-butanol (4 ml) and the mixture stirred at 110° C. for 18 hours. The cooled mixture was concentrated under reduced pressure and the residue suspended in water (10 ml) and neutralised using 2N hydrochloric acid. This aqueous suspension was extracted with ethyl acetate (3×30 ml), the combined organic extracts washed with sodium hydroxide solution (20 ml), brine (2×30 ml), dried (Na2SO4) and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel, using an elution gradient of dichloromethane:methanol (100:0 to 97.5:2.5) and the product suspended in ether and evaporated under reduced pressure. This solid was recrystallised from hexane/ethyl acetate to afford the title compound (72 mg, 17%) as a white solid.

Workup

  1. concentrationThe cooled mixture was concentrated under reduced pressure
  2. extractionThis aqueous suspension was extracted with ethyl acetate (3×30 ml)
  3. washthe combined organic extracts washed with sodium hydroxide solution (20 ml), brine (2×30 ml)
  4. dry with materialdried (Na2SO4)
  5. customevaporated under reduced pressure
  6. customThe crude product was purified by column chromatography on silica gel
  7. customevaporated under reduced pressure
  8. customThis solid was recrystallised from hexane/ethyl acetate

Sources & evidence

ORD record
ord-984400835fd7410f8231b6c1d08260c0
Source dataset
uspto-grants-2002_10
Patent number
US06458951B2

Linked notes

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