反应详情

8-Azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene hydrochloride from Example 65 (200 mg, 0.517 mmol) was stirred in DCM (2 mL) with triethylamine (145 μL, 1.04 mmol) for 1 h before the addition of 2-chloroethanesulfonyl chloride (84 mg, 0.52 mmol). After stirring for 1 h further triethylamine (73 μL, 0.52 mmol) was added and the mixture stirred for 18 h before diluting with DCM and washing with water followed by brine. The resultant solution was concentrated in vacuo to give a brown oil which was used in the subsequent step without purification. A portion of the brown oil (81 mg, 0.18 mmol) was stirred in 3 mL IMS at RT with 3-fluoro-azetidine hydrochloride (22 mg, 0.22 mmol) and triethylamine (56 μL, 0.4 mmol) for 18 h before being concentrated in vacuo. The resultant residue was dissolved in DCM and the solution washed with water then brine, dried (Na2SO4), filtered and concentrated in vacuo. The resultant light brown oil was subjected to flash chromatography (SiO2, gradient 0 to 2% MeOH in DCM) to give 204 as a white solid (37 mg, 40%). 1H NMR δ (ppm) (CDCl3): 8.49 (1H, d, J=8.30 Hz), 7.84 (1H, d, J=0.64 Hz), 7.62 (1H, s), 7.12 (1H, dd, J=8.34, 1.88 Hz), 7.00 (1H, d, J=1.83 Hz), 5.99-5.91 (1H, m), 5.19-5.13 (0.5H, m), 5.05-4.99 (0.5H, m), 4.49-4.46 (2H, m), 4.45-4.41 (2H, m), 4.26 (2H, t, J=8.24 Hz), 4.06 (2H, t, J=7.28 Hz), 3.80-3.63 (3H, m), 3.27-3.22 (1H, m), 3.21-3.16 (1H, m), 3.06-3.00 (2H, m), 2.97-2.90 (2H, m), 1.60-1.54 (6H, m). LCMS: RT=2.94 min, M+H+=516

1. additionwas added
2. washwashing with water
3. concentrationThe resultant solution was concentrated in vacuo
4. customto give a brown oil which
5. customwas used in the subsequent step without purification
6. concentrationbefore being concentrated in vacuo
7. dissolutionThe resultant residue was dissolved in DCM
8. washthe solution washed with water
9. dry with materialbrine, dried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated in vacuo