Oxalic Acid → HCID 67624953, compound

HRID 1457552Notes

Reaction equation

HRID 1457552 reaction equation
[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

Participants

9

Reactant 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

Product 1

HCID 67624953HCID 67624953, compound

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-8f713c221b2c41b3bfe653c01246a316
Source dataset
uspto-grants-1998_12
Patent number
US05849746

Reaction notes

Loading…