Potassium bis(trimethylsilyl)amide → 5-[2-Benzyloxy-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 990230Notes

Reaction equation

HRID 990230 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:11]([O:13][C:14]1[C:19]([C:20]2[NH:21][C:22](=[O:38])[C:23]3[C:24](=[C:26]([CH2:36][CH3:37])[N:27]([CH2:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=4)[N:28]=3)[N:25]=2)=[CH:18][C:17]([S:39]([N:42]2[CH2:47][CH2:46][N:45]([CH2:48][CH3:49])[CH2:44][CH2:43]2)(=[O:41])=[O:40])=[CH:16][N:15]=1)[CH3:12]>C(O)C1C=CC=CC=1>[CH2:11]([O:13][C:14]1[C:19]([C:20]2[NH:21][C:22](=[O:38])[C:23]3[C:24](=[C:26]([CH2:36][CH3:37])[N:27]([CH2:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=4)[N:28]=3)[N:25]=2)=[CH:18][C:17]([S:39]([N:42]2[CH2:47][CH2:46][N:45]([CH2:48][CH3:49])[CH2:44][CH2:43]2)(=[O:40])=[O:41])=[CH:16][N:15]=1)[C:12]1[CH:14]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

4

Reactant 2

HCID 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 1358163755-[2-Benzyloxy-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 77.7%

Reagents, catalysts & solvents 1

HCID 244Benzyl AlcoholSolvent

Procedure

Potassium bis(trimethylsilyl)amide (360 mg, 1.81 mmol) was added to a stirred solution of the title compound of Example 1 (200 mg, 0.36 mmol) in benzyl alcohol (5 ml) at 100° C. and the reaction mixture stirred for 14 hours, then allowed to cool. The resulting mixture was partitioned between dichloromethane (10 ml) and brine (10 ml), the phases separated, the aqueous phase extracted with dichloromethane (2×10 ml) and the combined organic solutions dried (Na2SO4) and evaporated under reduced pressure. The residual benzyl alcohol was removed by Kugelrohr distillation, then the crude product purified by column chromatography on silica gel, using dichloromethane:methanol (97.5:2.5) as eluant, to provide the title compound (86 mg, 39%) as a white solid. Found: C, 59.92; H, 5.64; N, 17.60. C31H34N8O4S; 0.40H2O requires C, 59.87; H, 5.64; N, 18.02%. δ (CDCl3): 1.05 (3H, t), 1.29 (3H, t), 2.41 (2H, q), 2.56 (4H, m), 3.05 (2H, q), 3.15 (4H, m), 5.68 (2H, s), 5.75 (2H, s), 7.10 (1H, d), 7.24 (1H, m), 7.42 (3H, m), 7.52 (2H, m), 7.64 (1H, m), 8.58 (1H, d), 8.65 (1H, s), 9.02 (1H, s), 10.58 (1H, s). LRMS: m/z 615 (M+1)+.

Workup

  1. temperatureto cool
  2. customThe resulting mixture was partitioned between dichloromethane (10 ml) and brine (10 ml)
  3. customthe phases separated
  4. extractionthe aqueous phase extracted with dichloromethane (2×10 ml)
  5. dry with materialthe combined organic solutions dried (Na2SO4)
  6. customevaporated under reduced pressure
  7. customThe residual benzyl alcohol was removed by Kugelrohr distillation
  8. customthe crude product purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-cf4b31d2f93941109cf24629b94e2a78
Source dataset
uspto-grants-2002_10
Patent number
US06458951B2

Reaction notes

Loading…