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

HRID 1350476Notes

Reaction equation

[CH2:1]([C:3]1[S:12][C:11]2[NH:10][C:9]3[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=3[NH:7][C:6](=S)[C:5]=2[N:4]=1)[CH3:2].FC(F)(F)S(OC)(=O)=O.[CH3:27][O:28][C:29]1[CH:30]=[C:31]([C@H:35]2[CH2:40][NH:39][CH2:38][CH2:37][NH:36]2)[CH:32]=[CH:33][CH:34]=1.N1C=CC=[CH:43][CH:42]=1>C(Cl)Cl>[CH2:1]([C:3]1[S:12][C:11]2[NH:10][C:9]3[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=3[N:7]=[C:6]([N:39]3[CH2:38][CH2:37][NH:36][C@@H:35]([CH2:31][CH2:32][C:33]4[CH:43]=[CH:42][CH:30]=[C:29]([O:28][CH3:27])[CH:34]=4)[CH2:40]3)[C:5]=2[N:4]=1)[CH3:2]

Participants

Conditions

Temperature: 35 °C

Procedure

By using a method similar to the Example 501, using 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, add methyl trifluoromethanesulfonate (4.2 g, 26.0 mmol) overnight, 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, give a red-brown solid. Dissolve the solid in 32.5 mL of pyridine to make 0.4 M of solution. Take 6.25 mL of the solution (2.5 mmol), mix with (S)-2-(3-methoxy-phenyl)-piperazine (550 mg, 2.5 mmol) and heat to 100° C. for 3 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 306 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: 7.21–7.16 (m, 1H), 7.08–6.96 (m, 2H), 6.91–6.86 (m, 1H), 6.80–6.71 (m, 3H), 6.65–6.64 (m, 1H), 5.40 (br, 1H), 4.35–4.25 (m, 2H), 3.78 (s, 3H), 3.16–2.69 (m, 10H), 1.79–1.76 (m, 2H), 1.29 (t, 3H, J=7.7 Hz).

Workup

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

Sources & evidence

ORD record: ord-4aa983bc7c164d27a8b5c93bcb0af768
Source dataset: uspto-grants-2007_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07214673B2

Reaction notes

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