Pyridine → (S)-2-Butyl-10-(3-phenethyl-piperazin-1-yl)-4H-3-thia-1,4,9-triaza-benzo[f]azulene

HRID 1350464Notes

Reaction equation

HRID 1350464 reaction equation
FC(F)(F)S(OC)(=O)=O.[CH2:10]([C:14]1[S:23][C:22]2[NH:21][C:20]3[CH:24]=[CH:25][CH:26]=[CH:27][C:19]=3[NH:18][C:17](=S)[C:16]=2[N:15]=1)[CH2:11][CH2:12][CH3:13].[CH2:29]([C@H:37]1[CH2:42][NH:41][CH2:40][CH2:39][NH:38]1)[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.N1C=CC=CC=1>ClCCl>[CH2:10]([C:14]1[S:23][C:22]2[NH:21][C:20]3[CH:24]=[CH:25][CH:26]=[CH:27][C:19]=3[N:18]=[C:17]([N:41]3[CH2:40][CH2:39][NH:38][C@@H:37]([CH2:29][CH2:30][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[CH2:42]3)[C:16]=2[N:15]=1)[CH2:11][CH2:12][CH3:13]

Participants

6

Reactant 4

HCID 1049PyridineHCID 9526Methyl triflateHCID 210934652-Butyl-4,9-dihydro-3-thia-1,4,9-triaza-benzo[f]azulene-10-thioneHCID 44828673(S)-2-Phenethylpiperazine

Product 1

HCID 136005542(S)-2-Butyl-10-(3-phenethyl-piperazin-1-yl)-4H-3-thia-1,4,9-triaza-benzo[f]azuleneYield 8.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add methyl trifluoromethanesulfonate (0.850 mL, 7.51 mmol) to a 0° C. solution of 2-Butyl-4,9-dihydro-3-thia-1,4,9-triaza-benzo[f]azulene-10-thione (1.45 g, 5.01 mmol) in anhydrous dichloromethane. Rinse solids into reaction with dichloromethane and stir allowing reaction to slowly reach ambient temperature. After an overnight period, concentrate under reduced pressure to afford crude methylated intermediate. Take 1.06 g of this intermediates (2.0 mmol), and combine the intermediate and 2-(S)-Phenethyl-piperazine (0.38 g, 2.0 mmol), with anhydrous pyridine, heat to 100° C. and stir. After an overnight period, cool to ambient temperature and concentrate under reduced pressure to an oil (2.16 g), followed by two chromatographic purifications, eluting with a gradient of a 8% solution of 2M ammonia in methanol, in dichloromethane (0–100% in dichloromethane), gives the title compound (0.078 g). Mass spectrum (APCI+, m/e): 446 (M+1); 1H NMR (300 MHz, DMSO-d6), δ (ppm): 7.79 (s, 1H), 7.31–7.10 (m, 5H), 6.90–6.74 (m, 3H), 6.71–6.64 (m, 1H), 4.14–3.92 (br. m, 1H), 3.44–3.22 (m, 1H), 2.93–2.52 (m, 10H), 1.65–1.49 (m, 4H), 1.36–1.20 (m, 2H, J=7.1 Hz), 0.82 (t, 3H, J=7.1 Hz).

Workup

  1. washRinse solids
  2. custominto reaction with dichloromethane
  3. customreaction to slowly reach ambient temperature
  4. concentrationconcentrate under reduced pressure
  5. customto afford crude methylated intermediate
  6. stirringstir
  7. waitAfter an overnight period
  8. concentrationconcentrate under reduced pressure to an oil (2.16 g)
  9. washeluting with a gradient of a 8% solution of 2M ammonia in methanol, in dichloromethane (0–100% in dichloromethane)

Sources & evidence

ORD record
ord-211ac1b9990f4bdeb998ae2b27574131
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

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