Etonitazene → N-(1-(2-(diethylamino)ethyl)-2-(4-ethoxybenzyl)-1H-benzo[d]-imidazol-5-ylcarbamothioyl)benzamide

HRID 2074450Notes

Reaction equation

HRID 2074450 reaction equation
[CH2:1]([O:3][C:4]1[CH:29]=[CH:28][C:7]([CH2:8][C:9]2[N:13]([CH2:14][CH2:15][N:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[C:12]3[CH:21]=[CH:22][C:23]([N+:25]([O-])=O)=[CH:24][C:11]=3[N:10]=2)=[CH:6][CH:5]=1)[CH3:2].[C:30]([N:38]=[C:39]=[S:40])(=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>O1CCCC1>[CH2:17]([N:16]([CH2:19][CH3:20])[CH2:15][CH2:14][N:13]1[C:12]2[CH:21]=[CH:22][C:23]([NH:25][C:39]([NH:38][C:30](=[O:37])[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)=[S:40])=[CH:24][C:11]=2[N:10]=[C:9]1[CH2:8][C:7]1[CH:28]=[CH:29][C:4]([O:3][CH2:1][CH3:2])=[CH:5][CH:6]=1)[CH3:18]

Participants

4

Reactant 2

HCID 13493EtonitazeneHCID 68284Benzoyl isothiocyanate

Product 1

HCID 16037889N-(1-(2-(diethylamino)ethyl)-2-(4-ethoxybenzyl)-1H-benzo[d]-imidazol-5-ylcarbamothioyl)benzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

{2-[2-(4-Ethoxy-benzyl)-5-nitro-benzoimidazol-1-yl]-ethyl}-diethyl-amine 7a (377 mg, 0.950 mmol) was reduced to the amine 8a as outlined above and the resulting ethanolic solution charged to a small, argon purged flask fitted with a magnetic stirbar. Anhydrous tetrahydrofuran (10 mL) added followed by dropwise addition of benzoyl isothiocyanate (178 mg, 1.093 mmol) and mixture stirred under Ar at ambient temperature for 3 hours then allowed to stand overnight at room temperature. 3-(Dimethylamino)propyl functionalized silica gel (205 mg, 0.286 mmol) added and mixture stirred for 1 hour, filtered and concentrated to yield crude. The product was purified using silica gel column chromatography eluting with 2.5% 2M NH3 in methanol/97.5% dichloromethane to afford a pale yellow oil. Trituration with diethyl ether/hexanes yielded an off white solid 20 N-(1-(2-(diethylamino)ethyl)-2-(4-ethoxybenzyl)-1H-benzo[d]-imidazol-5-ylcarbamothioyl)benzamide. Yield: 160 mg (31.7%) 1H NMR (DMSO) δ: 0.80 (t, 6H, J=7.0), 1.30 (t, 3H, J=7.0), 2.34-2.50 (2×m, 6H), 3.98 (q, 2H, J=7.0), 4.16 (t, 2H, J=6.3), 4.27 (s, 2H), 6.87 (d, 2H, J=8.4), 7.18 (d, 2H, J=8.5), 7.34 (d, 1H, J=8.4), 7.44-7.59 (2×m, 3H), 7.62-7.69 (m, 1H), 7.94-8.03 (2×m, 3H), 11.48 (br s, 1H), 12.60 (br s, 1H). MS (ESI): 530 (MH+, 100%)

Workup

  1. additioncharged to a small, argon purged flask
  2. customfitted with a magnetic stirbar
  3. waitto stand overnight at room temperature
  4. addition3-(Dimethylamino)propyl functionalized silica gel (205 mg, 0.286 mmol) added
  5. stirringmixture stirred for 1 hour
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield crude
  9. customThe product was purified
  10. washeluting with 2.5% 2M NH3 in methanol/97.5% dichloromethane
  11. customto afford a pale yellow oil

Sources & evidence

ORD record
ord-77b65131cee74d509a5d8727127d4b8d
Source dataset
uspto-grants-2011_04
Patent number
US07919510B2

Reaction notes

Loading…