Chlorosulfonic acid → 5-[3-Ethoxy-5-(4-methylpiperazinylsulfonyl)-thiophene-2-yl]-1-methyl-3-n-propyl-6,7-dihydro-1H-pyrazolo-[4,3-d]pyrimidin-7-one

HRID 1421483ノート

反応式

HRID 1421483 の反応式
C(OC1C=CS[C:5]=1[C:9]1[NH:10][C:11](=O)[C:12]2[N:17]([CH3:18])N=C(CCC)C=2N=1)C.ClS(O)(=O)=O.Cl[S:29]([C:32]1[S:36][C:35]([C:37]2[NH:38][C:39](=[O:50])[C:40]3[N:45]([CH3:46])[N:44]=[C:43]([CH2:47][CH2:48][CH3:49])[C:41]=3[N:42]=2)=[C:34]([O:51][CH2:52][CH3:53])[CH:33]=1)(=[O:31])=[O:30].ClS(C1SC(C2NC(=O)C3N(C)N=C(CCC)C=3N=2)=C(O)C=1)(=O)=O.CN1CCNCC1>CO>[CH2:52]([O:51][C:34]1[CH:33]=[C:32]([S:29]([N:10]2[CH2:9][CH2:5][N:17]([CH3:18])[CH2:12][CH2:11]2)(=[O:31])=[O:30])[S:36][C:35]=1[C:37]1[NH:38][C:39](=[O:50])[C:40]2[N:45]([CH3:46])[N:44]=[C:43]([CH2:47][CH2:48][CH3:49])[C:41]=2[N:42]=1)[CH3:53]

参加物

7

反応物 5

HCID 24638Chlorosulfonic acidHCID 531671-MethylpiperazineHCID 1354942865-(3-ethoxy-2-thienyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-oneHCID 1360726075-(5-chlorosulfonyl-3-hydroxythiophene-2-yl)-1-methyl-3-n-propyl-6,7-dihydro-1H-pyrazolo-[4,3-d]pyrimidin-7-oneHCID 1362054165-(5-chlorosulfonyl-3-ethoxythiophene-2-yl)-1-methyl-3-n-propyl-6,7-dihydro-1H-pyrazolo-[4,3-d]pyrimidin-7-one

生成物 1

HCID 1354268775-[3-Ethoxy-5-(4-methylpiperazinylsulfonyl)-thiophene-2-yl]-1-methyl-3-n-propyl-6,7-dihydro-1H-pyrazolo-[4,3-d]pyrimidin-7-one

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
50 °C

実験手順

Compound 4 (165 mg, 0.517 mmol) was added to chlorosulfonic acid (0.35 mL, 5.2 mmol) at 0° C. The mixture was stirred under nitrogen at 50° C. for 24 h. Ice was added and the mixture was extracted with a mixture of CH2Cl2 /MeOH (9:1), dried with Na2SO4. After evaporation of the solvent, a white solid was obtained which, by NMR analysis contained predominantly 5-(5-chlorosulfonyl-3-ethoxythiophene-2-yl)-1-methyl-3-n-propyl-6,7-dihydro-1H-pyrazolo-[4,3-d]pyrimidin-7-one and a small amount of 5-(5-chlorosulfonyl-3-hydroxythiophene-2-yl)-1-methyl-3-n-propyl-6,7-dihydro-1H-pyrazolo-[4,3-d]pyrimidin-7-one. This white solid (90 mg, 0.456 mmol) was added to a solution of methylpiperazine (137 mg, 1.37 mmol) in methanol (abs. 15 mL) and stirred at rt for 4 days. The solvent was evaporated, and the residue was dissolved in CH2Cl2 /MeOH (9:1) and washed with saturated Na2CO3. The aqueous layer was extracted with CH2Cl2 /MeOH (9:1). The organic layers were combined and dried with MgSO4. The residue obtained after evaporation of the solvent contained two compounds. Separation and purification was carried out by column chromatography (silica gel). Compound 5 was obtained as a white solid by elution with ethyl acetate; mp: 219-220° C.; 1H NMR (DMSO-d6) δ 0.94(t, J=7 Hz, 3H), 1.42(t, J=7 Hz,3 H), 1.74(sxt, J=7 Hz, 2 H), 2.18 (s, 3 H), 2.40 (m, 4 H), 2.76 (t, J=7 Hz, 2 H), 3.35 (m, 4 H), 4.14 (s, 3 H), 4.44 (q, J=7 Hz, 2 H), 7.72 (s, 1 H), 10.79 (br s, 1H); MS (m/z): 481 (MH+). The hydrochloride salt was prepared by adding a solution of HCl in dioxane (4.0 M, 0.2 mL) to a suspension of the free base (6.0 mg) in MeOH (1 mL) and stirring for 1 h. Following removal of the solvents under vacuum a white solid was obtained; mp: 225° C. (dec.).

後処理

  1. additionIce was added
  2. extractionthe mixture was extracted with a mixture of CH2Cl2 /MeOH (9:1)
  3. dry with materialdried with Na2SO4
  4. customAfter evaporation of the solvent
  5. customa white solid was obtained which
  6. stirringstirred at rt for 4 days
  7. customThe solvent was evaporated
  8. dissolutionthe residue was dissolved in CH2Cl2 /MeOH (9:1)
  9. washwashed with saturated Na2CO3
  10. extractionThe aqueous layer was extracted with CH2Cl2 /MeOH (9:1)
  11. dry with materialdried with MgSO4
  12. customThe residue obtained
  13. customafter evaporation of the solvent
  14. customSeparation and purification

出典と根拠

ORDレコード
ord-133d661c2487400f96b158d7305f5a0c
出典データセット
uspto-grants-2000_06
特許番号
US06077841

反応ノート

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