Sodium Iodide → 1-Benzyl-4-[3-(5-[1,2,4]triazol-4-yl-1H-indol-3-yl)-propyl]-piperazine-2-thione

HRID 609653Notes

Reaction equation

HRID 609653 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.C(N(CC)CC)C.S([O-])(=O)(=O)C.[CH2:36]([N:43]1[CH2:48][CH2:47][NH:46][CH2:45][C:44]1=[S:49])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C([O-])([O-])=O.[K+].[K+].[I-].[Na+]>C(O)(C)C.C1COCC1>[CH2:36]([N:43]1[CH2:48][CH2:47][N:46]([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)[CH2:45][C:44]1=[S:49])[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

10

Reactant 7

HCID 5238Sodium IodideHCID 8471Triethylamine2×HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chloride2×HCID 85257MethanesulfonateHCID 106083781-Benzylpiperazine-2-thioneHCID 106339143-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propan-1-ol

Product 1

HCID 105746711-Benzyl-4-[3-(5-[1,2,4]triazol-4-yl-1H-indol-3-yl)-propyl]-piperazine-2-thioneYield 39%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

In the same way as that described in Example 2, Step 4, using Intermediate 2 (150 mg, 0.62 mmol), methanesulphonyl chloride (96 μL, 1.24 mmol), triethylamine (172 μL, 1.24 mmol) and THF (80 mL), followed by more triethylamine (86 μL, 0.62 mmol) and methanesulphonyl chloride (48 μL, 0.62 mmol). The resultant crude mesylate was then treated with 1-benzylpiperazine-2-thione (255 mg, 1.24 mmol), K2CO3 (257 mg, 1.9 mmol), sodium iodide (93 mg, 0.62 mmol) and iso-propanol (20 mL). The crude produce was chromatographed on silica gel, eluting with CH2Cl2 :MeOH:NH3 (95:5:1), to give the title compound (104 mg) as a pale yellow foam, contaminated with some 1-benzylpiperazin-2-thione. The mixture of thioamides (104 mg) was dissolved in CH2Cl2 (25 mL) and treated with di-tert-butyldicarbonate (50 mg, 0.23 mmol). The mixture was stirred at room temperature for 2 h then the solvent removed in vacuo. The residue was chromatographed on silica gel, eluting with CH2Cl2 :MeOH (95:5), to afford the title compound (47 mg, 18%) as a colourless solid, mp. (MeOH) 201-203° C. C24H26N6S. 0.3(H2O) requires: C, 66.12; H, 6.15; N, 19.28%. Found: C, 66.09; H, 5.92; N, 19.23%. 1H NMR (360 MHz, d6 -DMSO) δ1.81-1.92 (2H, m), 2.42 (2H, t, J=7.1 Hz), 2.70-2.76 (4H, m), 3.37-3.42 (2H, m), 3.61 (2H, s), 7.27-7.38 (7H, m), 7.47 (1H, d, J=8.6 Hz), 7.77 (1H, s), 9.01 (2H, s), 11.07 (1H, br s). MS (ES+) (431, M+1).

Workup

  1. customThe crude produce
  2. customwas chromatographed on silica gel
  3. washeluting with CH2Cl2 :MeOH:NH3 (95:5:1)

Sources & evidence

ORD record
ord-1554a413d96a49fa860f69a0517232e7
Source dataset
uspto-grants-1999_12
Patent number
US05998415

Reaction notes

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