反应详情

A round bottom flask containing tert-butyl 2-hydroxyethyl(2-(7-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)ethyl)carbamate (220 mg, 0.574 mmol) under argon was charged with palladium on activated carbon (10% wt; 61.0 mg, 0.057 mmol). The mixture was purged with argon prior to the addition of EtOH (20 mL). The resulting suspension was evacuated using a pump, and hydrogen was let into the system via a balloon. The mixture was stirred under a balloon filled with hydrogen for 3 hours. The hydrogen balloon was removed, and methyl thiophene-2-carbimidothioate hydroiodide (327 mg, 1.147 mmol) was added to the reaction. The suspension was stirred at room temperature for 17 hours (overnight). After this time, the mixture was filtered through a pad of Celite, which was then rinsed with MeOH (10 mL). The filtrate was concentrated, and the residue was partitioned between saturated sodium bicarbonate solution (50 mL) and CH2Cl2 (100 mL). The mixture was transferred to a separatory funnel and extracted. After extraction, the organic layer was separated, dried (Na2SO4), filtered, and concentrated to give a dark residue. This residue was subjected to flash chromatography on silica gel using 2:98 MeOH/CH2Cl2 followed by 3.5:96.5 (2M NH3 in MeOH):CH2Cl2 to give a yellow solid (140 mg, 52.7%). 1H-NMR (DMSO-d6) δ 7.69 (brd, J=3.0 Hz, 1H), 7.57 (d, J=−5.1 Hz, 1H), 7.07 (dd, J=3.9, 4.8 Hz, 1H), 6.82-6.75 (m, 1H), 6.53-6.42 (m, 2H), 6.32 (brs, 2H), 4.73 (t, J=5.4 Hz, 1H), 3.54 (brs, 2H), 3.50-3.42 (m, 2H), 3.38 (brs, 4H, overlap with solvent peak), 3.27-3.19 (m, 2H), 3.08-2.96 (m, 2H), 1.41 (brs, 9H); ESI-MS (m/z, %): 463 (MH+, 100), 398 (60); HPLC purity: 96.4% a/a.

1. customThe mixture was purged with argon
2. additionto the addition of EtOH (20 mL)
3. customThe resulting suspension was evacuated
4. additionfilled with hydrogen for 3 hours
5. customThe hydrogen balloon was removed
6. stirringThe suspension was stirred at room temperature for 17 hours (overnight)
7. filtrationAfter this time, the mixture was filtered through a pad of Celite, which
8. washwas then rinsed with MeOH (10 mL)
9. concentrationThe filtrate was concentrated
10. customthe residue was partitioned between saturated sodium bicarbonate solution (50 mL) and CH2Cl2 (100 mL)
11. customThe mixture was transferred to a separatory funnel
12. extractionextracted
13. extractionAfter extraction
14. customthe organic layer was separated
15. dry with materialdried (Na2SO4)
16. filtrationfiltered
17. concentrationconcentrated
18. customto give a dark residue