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

HRID 990228Notes

Reaction equation

HRID 990228 reaction equation
[CH2:1]([O:3][C:4]1[C:9]([C:10]2[NH:11][C:12](=[O:28])[C:13]3[C:14](=[C:16]([CH2:26][CH3:27])[N:17]([CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=4)[N:18]=3)[N:15]=2)=[CH:8][C:7]([S:29]([N:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH3:39])[CH2:34][CH2:33]2)(=[O:31])=[O:30])=[CH:6][N:5]=1)[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:50](O)[CH2:51]CC>>[CH2:1]([O:3][C:4]1[C:9]([C:10]2[NH:11][C:12](=[O:28])[C:13]3[C:14](=[C:16]([CH2:26][CH3:27])[N:17]([CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=4)[N:18]=3)[N:15]=2)=[CH:8][C:7]([S:29]([N:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH3:39])[CH2:34][CH2:33]2)(=[O:30])=[O:31])=[CH:6][N:5]=1)[CH2:2][CH2:50][CH3:51]

Participants

4

Reactant 3

HCID 2631-ButanolHCID 3251421Potassium bis(trimethylsilyl)amideHCID 1355816594-{6-Ethoxy-5-[3-ethyl-6,7-dihydro-7-oxo-2-(2-pyridylmethyl)-2H-pyrazolo [4,3-d]pyrimidin-5-yl]-3-pyridylsulfonyl}-1-ethylpiperazine

Product 1

HCID 1364369065-[2-n-Butoxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridin-3-yl]-3-ethyl-2-(pyridin-2-yl)methyl-2,6-dihydro-7h-pyrazolo[4,3-d]pyrimidin-7-oneYield 69%

Conditions

Temperature
100 °C

Procedure

A mixture of the title compound of Example 1 (200 mg, 0.36 mmol), potassium bis(trimethylsilyl)amide (360 mg, 1.81 mmol) and n-butanol (5 ml) was stirred at 100° C. for 18 hours, then allowed to cool. The resulting mixture was evaporated under reduced pressure and the residue partitioned between water (5 ml) and dichloromethane (5 ml). The phases were separated and the aqueous layer extracted with dichloromethane (2×10 ml), then the combined organic solutions dried (MgSO4) and evaporated under reduced pressure. The residual yellow solid was purified by column chromatography on silica gel, using dichloromethane: methanol (97.5:2.5) as eluant, to yield the title compound (145 mg, 69%) as a white solid. Found: C, 57.43; H, 6.29; N. 18.82. C28H36N8O4S; 0.20 H2O requires C, 57.56; H, 6.28; N, 19.18%. δ (CDCl3): 1.03 (6H, 2×t), 1.30 (3H, t), 1.55 (2H, m), 1.94 (2H, m), 2.40 (2H, q), 2.55 (4H, m), 3.03 (2H, q), 3.13 (4H, m), 4.67 (2H, t), 5.68 (2H, s), 7.10 (1H, d), 7.22 (1H, m), 7.62 (1H, m), 8.56 (1H, d), 8.62 (1H, s), 9.01 (1H, s), 10.64 (1H, s). LRMS: m/z 581 (M+1)+.

Workup

  1. temperatureto cool
  2. customThe resulting mixture was evaporated under reduced pressure
  3. customthe residue partitioned between water (5 ml) and dichloromethane (5 ml)
  4. customThe phases were separated
  5. extractionthe aqueous layer extracted with dichloromethane (2×10 ml)
  6. dry with materialthe combined organic solutions dried (MgSO4)
  7. customevaporated under reduced pressure
  8. customThe residual yellow solid was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-df7e3bdbee0a4a36b3e544d4633b48d0
Source dataset
uspto-grants-2002_10
Patent number
US06458951B2

Reaction notes

Loading…