Pyridine → (S)-2-Ethyl-10-{3-[2-(4-methoxy-phenyl)-ethyl]-piperazin-1-yl}-4H-3-thia-1,4,9-triaza-benzo[f]azulene

HRID 1350474Notes

Reaction equation

HRID 1350474 reaction equation
FC(F)(F)S([O:6][CH3:7])(=O)=O.[CH2:10]([C:12]1[S:21][C:20]2[NH:19][C:18]3[CH:22]=[CH:23][CH:24]=[CH:25][C:17]=3[NH:16][C:15](=S)[C:14]=2[N:13]=1)[CH3:11].CO[C:29]1[CH:34]=[CH:33][C:32]([C@H:35]2[CH2:40][NH:39][CH2:38][CH2:37][NH:36]2)=[CH:31][CH:30]=1.N1C=CC=[CH:43][CH:42]=1>C(Cl)Cl>[CH2:10]([C:12]1[S:21][C:20]2[NH:19][C:18]3[CH:22]=[CH:23][CH:24]=[CH:25][C:17]=3[N:16]=[C:15]([N:39]3[CH2:38][CH2:37][NH:36][C@@H:35]([CH2:32][CH2:31][C:30]4[CH:29]=[CH:34][C:33]([O:6][CH3:7])=[CH:43][CH:42]=4)[CH2:40]3)[C:14]=2[N:13]=1)[CH3:11]

Participants

6

Reactant 4

HCID 1049PyridineHCID 9526Methyl triflate2×HCID 210934702-Ethyl-4,9-dihydro-3-thia-1,4,9-triaza-benzo {f}azulene-10-thioneHCID 51894795(S)-2-(4-Methoxy-phenyl)-piperazine

Product 1

HCID 136005544(S)-2-Ethyl-10-{3-[2-(4-methoxy-phenyl)-ethyl]-piperazin-1-yl}-4H-3-thia-1,4,9-triaza-benzo[f]azulene

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
35 °C

Procedure

Add methyl trifluoromethanesulfonate (4.2 g, 26.0 mmol) overnight, to a suspension of 2-ethyl-4,9-dihydro-3-thia-1,4,9-triaza-benzo {f}azulene-10-thione (3.4 g, 13.0 mmol) in 35 mL CH2Cl2, LC-MS showed still had 50% of starting material, added another 0.1 mL of methyl trifluoromethanesulfonate, and heated to 35° C. for 1 h. Concentrate the reaction mixture under reduced pressure to give a red-brown solid. Dissolve the solid in 32.5 mL of pyridine to make 0.4 M of solution. Take 5 mL of the solution (2.0 mmol), mix with (S)-2-(4-methoxy-phenyl)-piperazine (440 mg, 2.0 mmol) and heat to 100° C. for 2.5 hours. Cool the reaction to RT, concentrate down to a residue, which purify by flash chromatography on silica gel, gradient 100% CH2Cl2 to 100% mixed solvent of (CH2Cl2: 2N NH3/MeOH=20:1) over 55 min. give 250 mg of the title compound. Mass spectrum (APCI) (m/e): C25H29N5OS, Cacl. Mass: 447.21, Found: 448.2 (M+1); 1H NMR (300 MHz, CDCl3) δ ppm: 7.12–6.80 (m, 7H), 6.68–6.65 (m, 1H), 5.30 (br, 1H), 4.25 (m, 2H), 3.77 (s, 3H), 3.21–2.88 (m, 4H), 2.85–2.79 (m, 3H), 2.67–2.62 (m, 2H), 1.77–1.75 (m, 2H), 1.29 (t, 3H, J=7.3 Hz).

Workup

  1. concentrationConcentrate the reaction mixture under reduced pressure
  2. customto give a red-brown solid
  3. temperatureheat to 100° C. for 2.5 hours
  4. temperatureCool
  5. customthe reaction to RT
  6. concentrationconcentrate down to a residue, which
  7. custompurify by flash chromatography on silica gel, gradient 100% CH2Cl2 to 100%
  8. additionmixed solvent of (CH2Cl2: 2N NH3/MeOH=20:1) over 55 min.

Sources & evidence

ORD record
ord-25721dcb213c4cc29483e90543b9e603
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

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