Wu and Burgess
3,6-Dipiperidin-1-yl-xanthen-9-one (7). Yellow solid (3.0 g,
89%). 1H NMR (300 MHz, DMSO-d6) δ 7.86 (d, 2H, J ) 9.0 Hz),
6.98 (dd, 2H, J ) 9.0, 2.3 Hz), 6.74 (d, 2H, J ) 2.3 Hz), 3.41 (br,
8H), 1.60 (br, 12H); 13C NMR (75 MHz, DMSO-d6) δ 173.0, 157.7,
154.8, 126.8, 111.7, 111.3, 98.8, 47.8, 24.8, 23.9. MS (ESI) m/z
calcd for (M + H)+ C23H26N2O2 363.21; found 363.21.
7.30-7.23 (m, 7H), 3.87-3.85 (m, 8H), 3.79-3.77 (m, 8H), 2.06
(s, 3H); 13C NMR (125 MHz, CD3OD) δ 160.2, 159.9, 159.1, 137.2,
133.0, 132.8, 131.9, 131.4, 130.1, 127.3, 116.3, 115.8, 98.6, 67.4,
48.5, 19.6; IR (thin film) 1646, 1590, 1481, 1415, 1383, 1235, 1190
cm-1; HRMS (ESI) m/z calcd for (M - Cl)+ C28H29N2O3 441.2178;
found 441.2184.
Rosamine 3i. Green solid (47 mg, 53%). Rf ) 0.28 (10% MeOH/
CH2Cl2). 1H NMR (500 MHz, CD3OD) δ 7.58-7.45 (m, 3H), 7.26
(d, 1H, J ) 7.5 Hz), 7.16 (d, 2H, J ) 9.5 Hz), 6.95 (dd, 2H, J )
9.5, 2.2 Hz), 6.84 (d, 2H, J ) 2.2 Hz), 3.63 (br, 8H), 2.15 (br,
8H), 2.06 (s, 3H); 13C NMR (125 MHz, CD3OD) δ 159.3, 159.1,
156.4, 137.2, 133.4, 132.4, 131.9, 131.2, 130.1, 127.3, 116.6, 114.7,
97.9, 50.1, 26.3, 19.6. IR (thin film) 1648, 1596, 1413, 1378, 1344,
1189 cm-1; HRMS (ESI) m/z calcd for (M - Cl)+ C28H29N2O
409.2280; found 409.2277.
3,6-Dimorpholin-4-yl-xanthen-9-one (8). White solid (308 mg,
1
93%). H NMR (500 MHz, CDCl3) δ 8.14 (d, 2H, J ) 9.0 Hz),
6.86 (dd, 2H, J ) 9.0, 2.4 Hz), 6.67 (d, 2H, J ) 2.4 Hz), 3.86 (t,
8H, J ) 4.9 Hz), 3.33 (t, 8H, J ) 4.9 Hz); 13C NMR (125 MHz,
CDCl3) δ 175.1, 158.0, 155.3, 127.7, 114.1, 111.2, 100.0, 66.5,
47.5. MS (ESI) m/z calcd for (M + H)+ C21H23N2O4 367.17; found
367.17.
3,6-Bis(4-Boc-piperazin-1-yl)-xanthen-9-one (9). White solid
1
(680 mg, 60%). H NMR (500 MHz, CDCl3) δ 8.13 (d, 2H, J )
9.0 Hz), 6.86 (dd, 2H, J ) 9.0, 2.3 Hz), 6.66 (d, 2H, J ) 2.3 Hz),
3.59 (t, 8H, J ) 5.2 Hz), 3.37 (t, 8H, J ) 5.2 Hz), 1.47 (s, 18H);
13C NMR (125 MHz, CDCl3) δ 175.0, 158.1, 155.0, 154.6, 127.8,
114.0, 111.7, 100.3, 80.2, 47.3(2C), 28.4. MS (ESI) m/z calcd for
(M + H)+ C31H41N4O6 565.30; found 565.29.
Rosamine 4d. Green solid (107 mg, 68%). Rf ) 0.31 (10%
1
MeOH/CH2Cl2). H NMR (500 MHz, CDCl3) δ 7.94 (d, 2H, J )
8.3 Hz), 7.37 (d, 2H, J ) 9.5 Hz), 7.19-7.15 (m, 4H), 7.11 (d,
2H, J ) 8.3 Hz), 3.80 (br, 8H), 3.67-3.65 (m, 8H), 1.45 (s, 18H);
13C NMR (125 MHz, CDCl3) δ 158.2, 156.9, 156.8, 154.4, 138.2,
131.8, 131.0, 130.8, 115.4, 114.0, 98.3, 97.3, 80.7, 47.2(2C), 28.3;
IR (thin film) 1694, 1644, 1592, 1479, 1415, 1387, 1226, 1161
cm-1; HRMS (ESI) m/z calcd for (M - Cl)+ C37H44N4O5 751.2356;
found 751.2342.
3,6-Dipyrrolidin-1-yl-xanthen-9-one (10). Yellow solid (90 mg,
1
18%). H NMR (500 MHz, CDCl3) δ 8.08 (d, 2H, J ) 8.9 Hz),
6.50 (dd, 2H, J ) 8.9, 2.2 Hz), 6.28 (d, 2H, J ) 2.2 Hz), 3.34 (t,
8H, J ) 6.6 Hz), 2.01 (t, 8H, J ) 6.6 Hz); 13C NMR (125 MHz,
CDCl3) δ 175.0, 158.1, 151.6, 127.6, 111.5, 109.1, 96.5, 47.6, 25.4.
MS (ESI) m/z calcd for (M + H)+ C21H23N2O2 335.18; found
335.18.
Rosamine 12i. Green solid (93 mg, 98%). Rf ) 0.30 (10%
1
MeOH/CH2Cl2). H NMR (500 MHz, CD3OD) δ 7.58-7.45 (m,
3H), 7.29-7.19 (m, 7H), 3.86-3.81 (m, 8H), 3.74-3.72 (m, 4H),
2.07 (s, 3H), 1.85-1.75 (m, 6H); 13C NMR (125 MHz, CD3OD) δ
160.3, 159.5, 159.3, 158.7, 158.6, 137.3, 133.1, 133.0, 132.5, 131.9,
131.3, 130.1, 127.3, 116.8, 115.7, 115.6, 115.3, 98.7, 98.1, 67.4,
50.2, 48.4, 27.3, 25.3, 19.6; IR (thin film) 1646, 1590, 1480, 1415,
1387, 1236, 1189 cm-1; HRMS (ESI) m/z calcd for (M - Cl)+
C29H31N2O2 439.2386; found 439.2384.
General Procedure for the Synthesis of Rosamine Derivatives.
A Grignard reagent or lithium reagent (1.0 mmol) was added
dropwise over 1 min to the solution of 3,6-diamino-xanthen-9-one
(0.2 mmol) in 5 mL of THF at 0 °C. After stirring for 12 h at room
temperature, the reaction mixture was quenched by addition of 2
mL of 2 M aqueous HCl, stirred for 10 min, and then diluted with
20 mL of CH2Cl2. The organic layer was washed with water and
brine, dried over Na2SO4, and concentrated under reduced pressure.
The residue was purified by flash chromatography (5% to 10%
MeOH/CH2Cl2) to give the pure product.
Acknowledgment. We thank the TAMU/LBMS-Applications
Laboratory directed by Dr. Shane Tichy for assistance with mass
spectrometry. Support for this work was provided by The
National Institutes of Health (GM72041) and by The Robert
A. Welch Foundation.
Rosamine 1a. Purple solid (71 mg, 89%). Rf ) 0.28 (10%
1
MeOH/CH2Cl2). H NMR (500 MHz, CDCl3) δ 8.01 (d, 2H, J )
9.6 Hz), 7.22 (dd, 2H, J ) 9.6, 2.5 Hz), 6.77 (d, 2H, J ) 2.5 Hz),
3.66 (br, 8H), 2.87 (s, 3H), 1.72 (br, 12H); 13C NMR (125 MHz,
CDCl3) δ 157.6, 156.4, 156.3, 130.1, 114.8, 114.0, 96.8, 48.8, 25.8,
Supporting Information Available: Complete experimental
details and characterization data for all the new compounds.
This material is available free of charge via the Internet at
24.1, 14.8; IR (thin film) 1643, 1597, 1486, 1401, 1235, 1200 cm-1
;
HRMS (ESI) m/z calcd for (M - Cl)+ C24H29N2O 361.2280; found
361.2287.
Rosamine 2i. Green solid (94 mg, 98%). Rf ) 0.26 (10% MeOH/
CH2Cl2). 1H NMR (500 MHz, CD3OD) δ 7.59-7.46 (m, 3H),
JO800902J
8718 J. Org. Chem. Vol. 73, No. 22, 2008