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

HRID 1350475Notes

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].F[C:19]([F:26])(F)S(OC)(=O)=O.F[C:28]1[CH:29]=[C:30]([C@H:34]2[CH2:39][NH:38][CH2:37][CH2:36][NH:35]2)[CH:31]=[CH:32][CH:33]=1.[CH2:40](Cl)Cl>N1C=CC=CC=1>[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:38]3[CH2:37][CH2:36][NH:35][C@@H:34]([CH2:30][CH2:29][C:28]4[CH:33]=[CH:32][CH:31]=[C:19]([F:26])[CH:40]=4)[CH2:39]3)[C:5]=2[N:4]=1)[CH3:2]

Participants

Conditions

Temperature: 35 °C

Procedure

By using a method similar to the method of 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-fluoro-phenyl)-piperazine (520 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% CH2C12 to 100% mixed solvent of (CH2Cl2: 2N NH3/MeOH=20:1) over 55 min. give 412 mg of the title compound Mass spectrum (APCI) (m/e): C24H26FN5S, Cacl. Mass: 435.15, Found: 436.2 (M+1); 1H NMR (300 MHz, CDCl3) δ ppm: 7.24–6.85 (m, 7H), 6.66–6.65 (m, 1H), 5.30 (br, 1H), 4.25–4.15 (m, 2H), 3.20–2.68 (m, 10H), 1.90–1.75 (m, 2H), 1.29 (t, 3H, J=7.3 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% CH2C12 to 100%
additionmixed solvent of (CH2Cl2: 2N NH3/MeOH=20:1) over 55 min.

Sources & evidence

ORD record: ord-7f34a338d36044e78f2e8d2aa282a328
Source dataset: uspto-grants-2007_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07214673B2

Reaction notes

Loading…