Article
Journal of Medicinal Chemistry, 2010, Vol. 53, No. 24 8695
129.3, 128.7, 115.1, 114.0. EIMS m/z (rel intensity): 354 (Mþ, 100).
HRCIMS m/z calcd, 351.8847; found, 351.8851. HPLC purity:
99.44 (MeOH-H2O, 95:5).
product was obtained as a dark yellow solid (39 mg, 6.7%): mp
214-216 °C. IR (film): 3089, 1624, 1599, 1558, 1535, 1509, 1461,
1
1411, 1346, 862, 758 cm-1. H NMR (CDCl3): δ 9.16 (d, J =
2.3 Hz, 1 H), 8.90 (d, J = 2.3 Hz, 1 H), 8.41 (dd, J = 7.8 Hz, 2.1 Hz,
2,3-Dimethylphenazine (28). The general procedure was fol-
lowed. The compound was purified by silica gel column chro-
matography (1 in. of basic alumina was added to the top of the
silica gel column), eluting with hexane-chloroform, 1:1. The
product was obtained as a brown solid (62.2 mg, 20.3%): mp 170-
172 °C (lit47 mp 174-175 °C). 1H NMR (CDCl3): δ 8.22-8.19
(m, 2 H), 7.98 (s, 2 H), 7.81-7.77 (m, 2 H), 2.21 (s, 6 H). 13C
NMR (CDCl3): δ 142.9, 142.8, 141.8, 129.6, 129.4, 127.8, 20.6.
EIMS m/z (rel intensity): 208 (Mþ, 100). HPLC purity: 95.46%
(MeOH, 100).
3-Bromo-1-methylphenazine (29). The general procedure was
followed. The compound was purified by silica gel column chro-
matography (1 in. of basic alumina was added to the top of the
silica gel column), eluting with hexane-dichloromethane, 2:1.
The product was obtained as a yellow powder (59 mg, 19%): mp
1 H), 8.32 (dd, J = 7.8 Hz, 2.0 Hz, 1 H), 8.03-7.98 (m, 2 H). 13
C
NMR (CDCl3): δ 147.4, 144.8, 142.0, 141.4, 133.2, 132.6, 130.1,
129.6, 126.4, 126.1. ESIMS m/z (rel intensity): 304 (MHþ, 100).
HRESIMS m/z calcd, 302.9643; found, 302.9651. HPLC purity:
95.46% (MeOH-H2O, 70:30), 98.05% (MeOH-H2O, 90:10).
1,4-Dimethoxyphenazine (35). The general procedure was
followed. The compound was purified by silica gel column chro-
matography (with one-half inch of basic alumina on top) eluting
with dichloromethane. The product was obtained as a yellow solid
(68 mg, 17%): mp 179-181 °C (lit52 mp 185 °C). IR (film): 3056,
2994, 2935, 2835, 1626, 1606, 1485, 1463, 1397, 1383, 1247, 1231,
1092, 764, 752 cm-1. 1H NMR (CDCl3): δ 8.34 (m, 2 H), 7.79
(m, 2 H), 6.88 (m, 2 H), 4.05 (s, 3 H). 13C NMR (CDCl3): δ 148.7,
142.1, 136.9, 130.6, 129.8, 105.7, 56.2. EIMS m/z (rel intensity):
240 (Mþ, 86), 225 (Mþ-CH3, 100). CIMS m/z (rel intensity): 241
(MHþ, 100). HREIMS m/z calcd, 240.0899; found, 240.0900.
HPLC purity: 95.00% (MeOH, 100), 98.05% (MeOH-H2O,
90:10).
132-134 °C. IR (film): 1622, 1556, 1519, 1276, 764, 751 cm -1
.
1H NMR (CDCl3): δ 8.20-8.13 (m, 3 H), 7.82-7.78 (m, 2 H),
7.65 (s, 1 H), 2.85 (s, 3 H). 13C NMR (CDCl3): δ 143.6, 143.2,
142.5, 141.5, 139.6, 132.8, 130.8, 130.1, 129.9, 124.7, 17.3. EIMS
m/z (rel intensity): 274 (Mþ, 54), 272 (Mþ, 54), 179 (Mþ-Br, 100).
Anal. calcd for C13H9BrN2: C, 57.17; H, 3.32; N, 10.26. Found:
C, 57.01; H, 3.27; N, 10.14.
7,8-Dimethyl-1-methoxyphenazine (38). The general proce-
dure provided a solid that was dissolved in hot ethyl acetate
(70 mL). The solution was filtered through Celite. The Celite was
washed with ethyl acetate (∼200 mL) until the filtered solution
was light brown. Water (40 mL) was added, and the organic phase
was collected. The organic layer was washed with a saturated
aqueous solution of sodium bicarbonate (30 mL) and water (2 ꢀ
30 mL). The compound was purified by silica gel column
chromatography (1 in. of basic alumina on top), using ethyl
acetate-hexane, 1:1. The product was obtained as a yellow
powder (713 mg, 39.9%): mp 187-189 °C (dec). IR (film): 3043,
2916, 2834, 1636, 1606, 1560, 1515, 1477, 1469, 1442, 1400, 1109,
871, 775, 739 cm-1. 1H NMR (CDCl3): δ 8.12 (s, 1 H), 7.96 (s, 1 H),
7.78 (d, J = 8.8 Hz, 1 H), 7.7 (t, J = 7.6 Hz, 1 H), 7.01 (d, J =
7.3 Hz, 1 H), 4.15 (s, 3 H), 2.53 (s, 6 H). 13C NMR (CDCl3): δ
154.8, 143.5, 142.6, 141.8, 141.3, 141.1, 136.0, 129.4, 128.2,
127.3, 121.1, 105.6, 56.1, 20.4. CIMS m/z (rel intensity): 239 (Mþ,
100). HREIMS m/z calcd, 238.1106; found, 238.1108. Anal.
1,3-Dibromophenazine (30). The general procedure was fol-
lowed. The compound was purified by silica gel column chro-
matography (1 in. of basic alumina was added to the top of the
silica gel column), eluting with hexane-dichloromethane, 2:1.
The product was obtained as a yellow powder (124 mg, 36%):
mp 179-181 °C. IR (film): 3051, 1621, 1582, 1502, 1342, 1129,
956, 862, 757, 748 cm -1. 1H NMR (CDCl3): δ 8.38 (d, J = 2.0 Hz,
1 H), 8.32 (m, 1 H), 8.24 (m, 2 H), 7.89 (m, 2 H). 13C NMR
(CDCl3): δ 143.8, 143.5, 143.4, 139.4, 136.4, 131.8, 131.4, 131.3,
130.0, 129.2, 125.2, 123.8. EIMS m/z (rel intensity): 338 (Mþ,
100). Anal. calcd for C12H6Br2N2: C, 42.64; H, 1.79; N, 8.29.
Found: C, 42.46; H, 1.74; N, 8.20.
2-Methylphenazine (31).48 The general procedure was fol-
lowed. The compound was purified by silica gel column chro-
matography, eluting with ethyl acetate-hexane, 1:1. The com-
pound was obtained a light brown solid (49 mg, 9.7%): mp
107-108 °C (lit49 mp 117 °C). IR (film): 3026, 2976, 2920, 1633,
1604, 1511, 1482, 1466, 1437 cm-1. 1H NMR (300 MHz, CDCl3):
δ 8.24 (m, 2 H), 8.14 (d, J=8.9Hz,1H),8.00(s,1H),7.81(m,2H),
7.28 (d, J = 8.9 Hz, 1 H), 2.66 (s, 3 H). 13C NMR (75 MHz,
CDCl3): δ 143.5, 143.1, 142.8, 142.2, 141.1, 133.4, 130.1, 129.8,
129.5, 129.4, 128.9, 127.5, 22.1. EIMS m/z (rel intensity): 194
(Mþ, 100). HPLC purity: 98.48% (MeOH-H2O, 80-20).
2-Methoxyphenazine (32). The general procedure was followed.
The compound was purified by silica gel column chromatography,
eluting with ethyl acetate-dichloromethane, 1:1. The product was
obtained as light brown solid (26 mg, 6.5%): mp 116-118 °C
(lit50 mp 126 °C). 1H NMR (CDCl3): δ 8.14 (m, 2 H), 8.04 (d, J =
9.5 Hz, 1 H), 7.75 (m, 2 H), 7.47 (d, J = 2.7 Hz, 1 H), 7.34 (s, 1 H),
3.97 (s, 1 H). 13C NMR (CDCl3): δ 149.7, 143.3, 142.8, 141.6,
137.4, 135.2, 130.7, 130.4, 129.5, 128.9, 121.9, 111.7, 55.8. EIMS
m/z (rel intensity): 210 (Mþ, 100). HPLC purity: 99.40% (MeOH-
H2O, 80:20).
2,3-Dimethoxyphenazine (33). The general procedure was
followed. The compound was purified by silica gel column
chromatography, eluting with ethyl acetate-dichloromethane,
1.5:1. The product was obtained as a yellow solid (113 mg, 25%):
mp 215-227 °C (lit51 mp 230-231 °C). 1H NMR (CDCl3):
δ8.13-8.09(m, 2H),7.74-7.70 (m, 2 H), 7.34 (s, 2 H), 4.07 (s, 3 H).
13C NMR (CDCl3): δ 154.3, 141.8, 141.7, 128.9, 128.7, 105.1,
56.3. EIMS m/z (rel intensity): 240 (Mþ, 100). HPLC purity:
96.82% (MeOH-H2O, 80-20).
calcd for C15H14N2O 0.2H2O: C, 74.48; H, 6.00; N, 11.58.
3
Found: C, 74.14; H, 6.00; N, 11.76.
7,8-Dimethyl-3-bromo-1-methoxyphenazine (39). The general
procedure was followed. The solvent was removed in vacuo. The
compound was purified by silica gel column chromatography
(1 in. of basic alumina on top), eluting with dichloromethane-
ethyl acetate, 95:5. The product was obtained as a yellow
powder (919 mg, 47.5%); mp 229-231 °C. IR (film): 3054,
2986, 2918, 2849, 1691, 1632, 1593, 1557, 1516, 1465, 1442, 1421,
1265, 748, 705 cm-1. 1HNMR(CDCl3):δ8.09 (s, 1 H), 7.99 (d, J=
1.6 Hz, 1 H), 7.92 (s, 1 H), 4.16 (s, 3 H), 2.55 (s, 3 H), 2.54 (s, 3 H).
13C NMR (CDCl3): δ 155.2, 144.0, 143.8, 143.5, 142.1, 141.4,
128.4, 127.5, 123.7, 123.4, 110.4, 56.6, 20.6. EIMS m/z (rel
intensity): 319 (Mþ, 87), 317 (Mþ, 85) 237 (Mþ-HBr, 100).
HREIMS m/z calcd, 317.0289; found, 317.0291. HPLC purity:
97.8% (MeOH-H2O, 95:5), 96.11% (MeOH, 100).
7,8-Dichloro-1-methoxyphenazine (40). The general procedure
provided a solid that was dissolved in hot ethyl acetate (70 mL).
The solution was filtered through a column containing Celite 545
(∼1 in.) and basic alumina on top (∼1 in.). The Celite was washed
with ethyl acetate until the filtered solution was light in color. The
organic solutions were combined and washed with saturated sodium
bicarbonate (50 mL) and water (50 mL). The compound was
purified by silica gel column chromatography, eluting with ethyl
acetate-hexane, 1:3. The product was obtained as a dark yellow
powder (539 mg, 19.4%): mp 245- 247 °C. IR (film): 3041, 2964,
1619, 1555, 1518, 1503, 1466, 1413, 1396, 1284, 1254, 1111, 885,
763 cm-1. 1H NMR (CDCl3): δ 8.53 (s, 1 H), 8.35 (s, 1 H), 7.79
(d, 2 H), 7.11 (t, J = 4.33 Hz, 1 H). 13C NMR (CDCl3): δ 155.0,
144.5, 141.8, 140.5, 137.1, 135.7, 135.0, 131.5, 130.2, 129.5, 121.3,
1-Bromo-3-nitrophenazine (34). The general procedure was
followed. The compound was purified by silica gel column
chromatography, eluting with ethyl acetate-hexane, 1.5:1. The