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2.1, 0.7 Hz, 1H), 7.90 (td, J ¼ 7.6, 1.9 Hz, 1H), 7.49 (dddd, J ¼ 8.3, starting from 57 (54% yield, yellow powder). H NMR (400 MHz,
7.4, 4.9, 1.9 Hz, 1H), 7.17 (dd, J ¼ 7.6, 1.1 Hz, 1H), 7.14–7.03 (m, CDCl3, Me4Si) d 9.04 (d, J ¼ 2.1 Hz, 1H), 8.69 (d, J ¼ 2.1 Hz, 1H),
1H), 5.39 (p, J ¼ 4.4 Hz, 1H), 4.30–3.79 (m, 4H), 2.00 (d, J ¼ 6.92–6.76 (m, 3H), 3.91 (d, J ¼ 25.6 Hz, 4H), 3.42 (s, 1H), 2.23 (s,
21.8 Hz, 4H). LC-MS(ESI) m/z 493.1(M + Na)+. HPLC purity 99%. 3H), 1.94 (s, 4H). LC-MS(ESI) m/z 506.1 (M + Na)+. HPLC purity 98%.
4.1.1.26 2-(4-(4-Fluorophenoxy)piperidin-1-yl)-8-nitro-6-(tri-
4.1.1.34 2-(4-(2,6-Diuorophenoxy)piperidin-1-yl)-8-nitro-6-
uoro-methyl)-4H-benzo[e][1,3]-thiazin-4-one (3b). Method (trie-oromethyl)-4H-benzo-[e][1,3]thiazin-4-one (3j). Method
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4.1.2 starting from 50 (47% yield, yellow powder). 1H NMR (400 4.1.2 starting from 58 (49% yield, yellow powder). H NMR (400
MHz, CDCl3, Me4Si) d 9.12 (dd, J ¼ 2.1, 0.8 Hz, 1H), 8.78 (dd, J ¼ MHz, CDCl3, Me4Si) d 9.04 (d, J ¼ 2.1 Hz, 1H), 8.69 (d, J ¼ 2.1 Hz,
2.1, 0.8 Hz, 1H), 8.12–8.03 (m, 2H), 7.19–7.10 (m, 2H), 5.38 (tt, J ¼ 1H), 7.00–6.80 (m, 3H), 4.50 (s, 1H), 3.98 (s, 4H), 1.97 (d, J ¼
6.9, 3.6 Hz, 1H), 4.34–3.68 (m, 4H), 2.11 (d, J ¼ 49.2 Hz, 4H). ESI 42.4 Hz, 4H). LC-MS(ESI) m/z 510.1 (M + Na)+. HPLC purity 99%.
HRMS exact mass calcd. For (C20H19F3N4O5S + Na)+ requires m/z
492.06, found m/z 492.0620. HPLC purity 99%.
4.1.1.35 8-Nitro-2-(4-(pyridin-2-yloxy)piperidin-1-yl)-6-(triuoro-
methyl)-4H-benzo[e][1,3]thiazin-4-one (3k). Method 4.1.2 starting
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4.1.1.27 2-(4-(3-Fluorophenoxy)piperidin-1-yl)-8-nitro-6-(tri- from 79 (52% yield, yellow powder). H NMR (400 MHz, CDCl3,
uorome-thyl)-4H-benzo[e][1,3]-thiazin-4-one (3c). Method Me4Si) d 9.11 (d, J ¼ 2.3 Hz, 1H), 8.78 (d, J ¼ 2.3 Hz, 1H), 8.00 (d, J
4.1.2 starting from 51 (55% yield, yellow powder). 1H NMR ¼ 3.4 Hz, 1H), 7.30 (d, J ¼ 8.7 Hz, 1H), 7.15 (d, J ¼ 8.3 Hz, 1H),
(400 MHz, CDCl3, Me4Si) d 9.04 (d, J ¼ 2.0 Hz, 1H), 8.70 (d, J ¼ 7.03(dd, J ¼ 8.6, 3.1 Hz, 1H), 4.72 (p, J ¼ 4.6 Hz, 1H), 4.00 (dt, J ¼
2.0 Hz, 1H), 7.25–7.19 (m, 1H), 6.70–6.54 (m, 3H), 4.63 (t, J ¼ 13.6, 6.3 Hz, 2H), 2.06 (d, J ¼ 16.0 Hz, 4H), 1.35–1.24 (m, 2H). LC-
4.2 Hz, 1H), 4.17–3.48 (m, 4H), 1.98 (d, J ¼ 10.3 Hz, 4H). LC- MS(ESI): m/z 475.1 (M + Na)+. HPLC purity 95%.
MS(ESI): m/z 493.1 (M + Na)+. HPLC purity 99%.
4.1.1.36 2-(4-((5-Fluoropyridin-2-yl)oxy)piperidin-1-yl)-8-nitro-
4.1.1.28 2-(4-(2-Chlorophenoxy)piperidin-1-yl)-8-nitro-6-(tri- 6-(tri-uoromethyl)-4H-benzo[e][1,3]thiazin-4-one (3l). Method
uo-romethyl)-4H-benzo[e][1,3]thiazin-4-one (3d). Method 4.1.2 4.1.2 starting from 80 (45% yield, yellow powder).1H NMR (400
starting from 52 (51% yield, yellow powder). 1H NMR (400 MHz, CDCl3, Me4Si) d 9.11 (d, J ¼ 2.1 Hz, 1H), 8.78 (d, J ¼ 2.1 Hz,
MHz, CDCl3, Me4Si) d 9.04 (d, J ¼ 2.1 Hz, 1H), 8.70 (d, J ¼ 1H), 8.11 (d, J ¼ 3.1 Hz, 1H), 7.43 (d, J ¼ 8.7 Hz, 1H), 7.15 (dd, J ¼
2.1 Hz, 1H), 7.86–7.74 (m, 1H), 7.50–7.37 (m, 2H), 7.29 (ddd, J 8.7, 3.1 Hz, 1H), 4.72 (p, J ¼ 4.3 Hz, 1H), 4.00 (dt, J ¼ 13.6, 6.7 Hz,
¼ 8.5, 6.4, 2.2 Hz, 1H), 5.38 (q, J ¼ 4.9 Hz, 1H), 4.02 (d, J ¼ 2H), 2.06 (d, J ¼ 15.5 Hz, 4H), 1.35–1.24 (m, 2H). LC-MS(ESI): m/z
11.6 Hz, 4H), 2.05 (s, 4H). LC-MS(ESI): m/z 486.0 (M + H)+. 471.1 (M + Na)+. HPLC purity 98%.
HPLC purity 96%.
4.1.1.37 2-(4-((4-Methylpyrimidin-2-yl)oxy)piperidin-1-yl)-8-
(3m).
4.1.1.29 2-(4-(2-Bromophenoxy)piperidin-1-yl)-8-nitro-6-(tri- nitro-6-(triuoromethyl)-4H-benzo[e][1,3]thiazin-4-one
uo-romethyl)-4H-benzo[e][1,3]thiazin-4-one (3e). Method 4.1.2 Method 4.1.2 starting from 85 (58% yield, yellow powder). 1H
starting from 53 (46% yield, yellow powder). 1H NMR (400 NMR (400 MHz, CDCl3, Me4Si) d 9.11 (d, J ¼ 2.1 Hz, 1H), 8.77
MHz, CDCl3, Me4Si) d 9.03 (d, J ¼ 2.1 Hz, 1H), 8.69 (d, J ¼ (d, J ¼ 2.1 Hz, 1H), 8.35 (dd, J ¼ 9.2, 5.0 Hz, 1H), 6.85 (d, J ¼
2.1 Hz, 1H), 7.51 (dd, J ¼ 7.9, 1.6 Hz, 1H), 7.26–7.19 (m, 1H), 5.0 Hz, 1H), 4.34 (dd, J ¼ 17.2, 10.2 Hz, 1H), 4.11 (p, J ¼ 6.8 Hz,
6.94–6.79 (m, 2H), 4.74 (s, 1H), 2.17–1.84 (m, 4H), 1.55 (s, 4H). 4H), 2.48 (d, J ¼ 7.4 Hz, 4H), 1.60 (s, 3H). LC-MS(ESI) m/z 490.1
LC-MS(ESI) m/z 552.0 (M + Na)+. HPLC purity 97%.
(M + Na)+. HPLC purity 97%.
4.1.1.30 8-Nitro-6-(triuoromethyl)-2-(4-(2-(triuoromethyl)
4.1.1.38 8-Nitro-6-(triuoromethyl)-2-(4-((4-(triuoromethyl)
pheno-xy)piperidin-1-yl)-4H-benzo[e][1,3]thiazin-4-one (3f). Method pyrimidin-2-yl)oxy)piperidin-1-yl)-4H-benzo[e][1,3]thiazin-4-one
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4.1.2 starting from 54 (54% yield, yellow powder). H NMR (400 (3n). Method 4.1.2 starting from 88 (52% yield, yellow pow-
MHz, CDCl3, Me4Si) d 9.04 (d, J ¼ 2.1 Hz, 1H), 8.69 (d, J ¼ 2.1 Hz, der).1H NMR (400 MHz, CDCl3, Me4Si) d 9.11 (d, J ¼ 2.1 Hz,
1H), 7.55 (dd, J ¼ 7.8, 1.6 Hz, 1H), 7.44 (td, J ¼ 7.9, 1.7 Hz, 1H), 1H), 8.79 (dd, J ¼ 13.5, 3.5 Hz, 2H), 7.33 (d, J ¼ 4.9 Hz, 1H),
7.03–6.90 (m, 2H), 4.83 (s, 1H), 2.24–1.84 (m, 4H), 1.54 (s, 4H). LC- 5.50 (p, J ¼ 4.7 Hz, 1H), 4.67–3.90 (m, 4H), 2.17 (s, 4H). ESI
MS(ESI) m/z 520.1 (M + H)+. HPLC purity 97%.
HRMS exact mass calcd. For (C19H13F6N5O3S + Na)+ requires
4.1.1.31 8-Nitro-2-(4-(o-tolyloxy)piperidin-1-yl)-6-(triuoro- m/z 544.05, found m/z 544.0482. HPLC purity 97%.
methyl)-4H-benzo[e][1,3]thiazin-4-one (3g). Method 4.1.2 4.1.1.39 (4-((4-Chloropyrimidin-2-yl)oxy)piperidin-1-yl)-8-nitro-
starting from 55 (57% yield, yellow powder). 1H NMR (400 6-(triuoromethyl)-4H-benzo[e][1,3]thiazin-4-one (3o). Method
MHz, CDCl3, Me4Si) d 9.04 (d, J ¼ 2.1 Hz, 1H), 8.69 (d, J ¼ 4.1.2 starting from 87 (47% yield, yellow powder).1H NMR (400
2.1 Hz, 1H), 7.17–7.03 (m, 2H), 6.88–6.72 (m, 2H), 4.67 (s, MHz, CDCl3, Me4Si) d 9.12 (d, J ¼ 2.1 Hz, 1H), 8.78 (d, J ¼ 2.1 Hz,
1H), 3.88 (s, 4H), 2.19 (s, 3H), 1.99 (s, 4H). LC-MS(ESI) m/z 1H), 8.36 (d, J ¼ 5.7 Hz, 1H), 6.70 (d, J ¼ 5.7 Hz, 1H), 5.57 (tt, J ¼
466.1 (M + H)+. HPLC purity 97%.
6.8, 3.6 Hz, 1H), 4.12 (q, J ¼ 7.2 Hz, 4H), 2.22–2.01 (m, 4H). ESI
4.1.1.32 8-Nitro-2-(4-(4-(triuoromethoxy)phenoxy)piperidin-1- HRMS exact mass calcd. For (C18H13F4O3S + Na)+ requires m/z
yl)-6-(triuoromethyl)-4H-benzo[e][1,3]thiazin-4-one (3h). Method 494.05, found m/z 494.0526. HPLC purity 99%.
4.1.2 starting from 56 (48% yield, yellow powder). 1H NMR (400
MHz, CDCl3, Me4Si) d 9.03 (d, J ¼ 2.1 Hz, 1H), 8.70 (d, J ¼ 2.1 Hz,
5 Biology
5.1 Mycobacterium tuberculosis H37Ra MIC assay
1H), 7.16–7.06 (m, 2H), 6.92–6.82 (m, 2H), 4.62 (t, J ¼ 4.1 Hz, 1H),
4.37–3.63 (m, 4H), 2.00 (s, 4H). LC-MS(ESI) m/z 536.1 (M + H)+.
HPLC purity 96%.
The MICs against Mycobacterium tuberculosis H37Ra were
4.1.1.33 2-(4-(2-Fluoro-4-methylphenoxy)piperidin-1-yl)-8-nitro- detected by the microplate Alamar blue assay. Compounds were
6-(tri-uoromethyl)-4H-benzo[e][1,3]thiazin-4-one (3i). Method 4.1.2 dissolved in dimethyl sulfoxide (DMSO) with concentrations of
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RSC Adv., 2018, 8, 11163–11176 | 11173