Oxalic Acid → HCID 67624953、化合物

HRID 1457552ノート

反応式

HRID 1457552 の反応式
[N:1]1[N:2]=[CH:3][N:4]([C:6]2[CH:7]=[C:8]3[C:12](=[CH:13][CH:14]=2)[NH:11][CH:10]=[C:9]3[CH2:15][CH2:16][CH2:17]O)[CH:5]=1.CS(Cl)(=O)=O.[CH2:24]([N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH:32]1[CH2:37][N:38]([CH3:40])[CH3:39])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[C:41]([OH:46])(=[O:45])[C:42]([OH:44])=[O:43]>C1COCC1.CN(C=O)C.C(OCC)(=O)C.C(N(CC)CC)C>[C:41]([OH:46])(=[O:45])[C:42]([OH:44])=[O:43].[CH2:24]([N:31]1[CH2:36][CH2:35][N:34]([CH2:17][CH2:16][CH2:15][C:9]2[C:8]3[C:12](=[CH:13][CH:14]=[C:6]([N:4]4[CH:3]=[N:2][N:1]=[CH:5]4)[CH:7]=3)[NH:11][CH:10]=2)[CH2:33][CH:32]1[CH2:37][N:38]([CH3:40])[CH3:39])[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

参加物

9

反応物 4

HCID 971Oxalic AcidHCID 31297Methanesulfonyl chlorideHCID 106339143-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propan-1-olHCID 53694502N,N-Dimethyl-1-(phenylmethyl)-2-piperazinemethanamine

生成物 1

HCID 67624953HCID 67624953、化合物

試薬・触媒・溶媒 4

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒HCID 8471Triethylamine溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
25 °C

実験手順

To a solution of 3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propan-1-ol (0.490 g, 2.02 mmol) in THF (100 mL) was added triethylamine (0.62 ml), 6.0 mmol) followed by methanesulphonyl chloride (0.35 mL, 3.03 mmol) and the mixture stirred at 25° C. for 1.5 h. The reaction mixture was filtered and the solvent evaporated. The residue was dissolved in DMF (50 mL) and potassium carbonate (0.35 g) added followed by a solution of 1-benzyl-2-(N,N-dimethylaminomethyl)piperazine (step 2) (0.52 g, 2.22 mmol) in DMF (20 mL). The reaction was heated at 85° C. under N2 for 4 days. The solvent was then removed in vacuo and the residue taken up in ethyl acetate (50 mL) and washed with H2O (3×20 mL). The organic layer was dried (MgSO4) and evaporated. The residue was chromatographed on silica eluting with CH2Cl2 →6% MeOH-1% NH3 --CH2Cl2 to obtain a pale yellow oil that was treated with a solution of oxalic acid in ethyl acetate to obtain a white solid that was filtered and dried to obtain 4-benzyl-3-(N,N-dimethylaminomethyl)-1-[3-(5-(1,2,4-triazol-4-yl) -1H-indol-3-yl)propyl]piperazine oxalate, 105 mg. 1H nmr (free base, 250 MHz, CDCl3) δ 1.92 (2H, m), 2.05-2.9 (13H, m), 2.21 (6H, s), 3.22 (1H, d), 4.20 (1H, d), 7.12 (2H, m), 7.23-7.31 (5H, m), 7.46 (1H, d, J=4 Hz), 7.55 (1H, d, J=1 Hz), 8.38 (1H, br s), 8.46 (2H, s). MS (m/z) 458 (M+1).

後処理

  1. filtrationThe reaction mixture was filtered
  2. customthe solvent evaporated
  3. dissolutionThe residue was dissolved in DMF (50 mL)
  4. additionpotassium carbonate (0.35 g) added
  5. temperatureThe reaction was heated at 85° C. under N2 for 4 days
  6. customThe solvent was then removed in vacuo
  7. washwashed with H2O (3×20 mL)
  8. dry with materialThe organic layer was dried (MgSO4)
  9. customevaporated
  10. customThe residue was chromatographed on silica eluting with CH2Cl2 →6% MeOH-1% NH3
  11. customCH2Cl2 to obtain a pale yellow oil that
  12. customto obtain a white solid
  13. filtrationthat was filtered
  14. customdried

出典と根拠

ORDレコード
ord-8f713c221b2c41b3bfe653c01246a316
出典データセット
uspto-grants-1998_12
特許番号
US05849746

反応ノート

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