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. Author manuscript; available in PMC: 2012 Sep 12.
Published in final edited form as: ACS Comb Sci. 2011 Jul 13;13(5):501–510. doi: 10.1021/co200090p

Table 2.

Desketoraloxifene Analog Librarya

graphic file with name nihms309970u3.jpg
product 6/7 R1 R2 R3 NR4R5 ion HRMS HRMS (calcd) HRMS (found) purity (%)e yield (%)f
6{1} H H H piperidino [M+H]+ 413.1813 414.1894 98 83
6{2} H H H morpholino [M+H]+ 415.1606 416.1682 >99 78
6{3} H H H pyrrolidino [M+H]+ 399.1657 400.1732 92 81h
6{4} H H H NMe2 [M+H]+ 373.1500 374.1576 98 79
6{5} H H 4-MeO piperidino [M+H]+ 443.1919 444.1987 98 83
7{1}b H H 4-OH piperidino [M+H]+ 429.1762 430.1835 98 27g
6{6} H H 4-MeO morpholino [M+H]+ 445.1712 446.1788 >99 73
7{2}b H H 4-OH morpholino [M+H]+ 431.1555 432.1636 75 23g
6{7} H H 4-MeO pyrrolidino [M]+ 429.1762 429.1765 85
7{3}b H H 4-OH pyrrolidino [M+H]+ 415.1606 416.1681 74 46g
6{8} H H 4-MeO NMe2 [M+H]+ 403.1606 404.1673 98 81
7{4}b H H 4-OH NMe2 [M+H]+ 389.1449 390.1528 70 56
6{9} H H 3-MeO piperidino [M]+ 443.1919 443.1916 78
7{5}b H H 3-OH piperidino [M+H]+ 429.1763 430.1843 >99 53g
6{10} H H 3-MeO morpholino 73
7{6}b H H 3-OH morpholino [M+H]+ 431.1555 432.1636 >99 47
6{11} H H 3-MeO pyrrolidino 76
7{7}b H H 3-OH pyrrolidino [M+H]+ 415.1606 416.1682 98 35g
6{12} H H 3-MeO NMe2 69
7{8}b H H 3-OH NMe2 [M+H]+ 389.1450 390.1525 >99 51g
6{13} H H 2-MeO piperidino [M]+ 443.1919 443.1917 76
7{9}b H H 2-OH piperidino [M+H]+ 429.1763 430.1841 92 17g
6{14} H H 2-MeO morpholino 78
7{10}b H H 2-OH morpholino ndi
6{15} H H 2-MeO pyrrolidino 67
7{11}b H H 2-OH pyrrolidino ndi
6{16} H H 2-MeO NMe2 71
7{12}b H H 2-OH NMe2 [M+H]+ 389.1450 390.1525 >99 12g
6{17} MeO H 4-MeO piperidino [M+H]+ 473.2025 474.2050 99 87
7{13}c OH H 4-OH piperidino [M+H]+ 445.1712 446.1787 99 38g
6{18} MeO H 4-MeO morpholino 74h
7{14}c OH H 4-OH morpholino [M+H]+ 447.1504 448.1579 87 56g
6{19} MeO H 4-MeO pyrrolidino [M]+ 429.1762 429.1768 81
7{15}c OH H 4-OH pyrrolidino [M+H]+ 431.1555 432.1638 86 16g
6{20} MeO H 4-MeO NMe2 81
7{16}c OH H 4-OH NMe2 ndi
6{21} MeO H 3-MeO piperidino [M]+ 473.2025 473.2031 86
7{17}c OH H 3-OH piperidino [M+H]+ 445.1712 446.1790 94 48g
6{22} MeO H 3-MeO morpholino [M+H]+ 475.1817 476.1890 97 83h
6{23} MeO H 3-MeO pyrrolidino 71
6{24} MeO H 3-MeO NMe2 [M+H]+ 433.1712 434.1790 96 82
7{18}c OH H 3-OH NMe2 [M+H]+ 405.1399 406.1475 89 17g
6{25} MeO H 2-MeO piperidino [M+H]+ 473.2025 474.2095 99 87
7{19}c OH H 2-OH piperidino [M+H]+ 445.1712 446.1787 95 52
6{26} MeO H 2-MeO morpholino 81h
6{27} MeO H 2-MeO pyrrolidino [M+H]+ 459.1868 460.1946 98 83
7{20}c OH H 2-OH pyrrolidino ndi
6{28} MeO H 2-MeO NMe2 [M]+ 433.1712 433.1720 83
7{21}c OH H 2-OH NMe2 [M+H]+ 405.1399 406.1475 93 42g
6{29} MeO H 3,5-(MeO)2 piperidino [M]+ 503.2130 503.2132 77
7{22}d OH H 3,5-(OH)2 piperidino [M+H]+ 461.1661 462.1737 33 7g
6{30} MeO H 3,5-(MeO)2 morpholino 78
6{31} MeO H 3,5-(MeO)2 pyrrolidino 73
6{32} MeO H 3,5-(MeO)2 NMe2 73
7{23}d OH H 3,5-(OH)2 NMe2 [M+H]+ 421.1348 422.1362 82 21g
6{33} H MeO 4-MeO piperidino [M+H]+ 473.2025 474.2105 98 83
7{24}c H OH 4-OH piperidino [M+H]+ 445.1712 446.1793 97 78
6{34} H MeO 4-MeO morpholino 78
7{25}c H OH 4-OH morpholino [M+H]+ 447.1504 448.1585 55 43g
6{35} H MeO 4-MeO pyrrolidino 75
7{26}c H OH 4-OH pyrrolidino [M+H]+ 431.1555 432.1633 13 38g
6{36} H MeO 4-MeO NMe2 76
7{27}c H OH 4-OH NMe2 [M+H]+ 405.1399 406.1471 30 47
6{37} H MeO 2-MeO piperidino [M]+ 473.2025 473.2019 78
7{28}c H OH 2-OH piperidino [M+H]+ 445.1712 446.1914 97 37g
6{38} H MeO 2-MeO morpholino 77
7{29} H OH 2-OH morpholino [M+H]+ 447.1504 448.1712 97 49g
6{39} H MeO 2-MeO pyrrolidino 81
7{30}c H OH 2-OH pyrrolidino [M+H]+ 431.1555 432.1703 92 35g
6{40} H MeO 2-MeO NMe2 82
7{31}c H OH 2-OH NMe2 [M+H]+ 405.1399 406.1538 99 31g
6{41} MeO MeO 4-MeO piperidino [M+H]+ 503.2130 504.2146 95 76
7{32}d OH OH 4-OH piperidino [M+H]+ 461.1661 462.1732 >99 12g
6{42} MeO MeO 4-MeO morpholino 75h
7{33}d OH OH 4-OH morpholino [M+H]+ 463.1453 464.1471 97 53g
6{43} MeO MeO 4-MeO pyrrolidino [M]+ 489.1974 489.1981 79
7{34}d OH OH 4-OH pyrrolidino ndi
6{44} MeO MeO 4-MeO NMe2 69
7{35}d OH OH 4-OH NMe2 ndi
6{45} MeO MeO 3-MeO piperidino [M]+ 503.2130 503.2134 79
7{36}d OH OH 3-OH piperidino ndi
6{46} MeO MeO 3-MeO morpholino 81h
6{47} MeO MeO 3-MeO pyrrolidino [M]+ 489.1974 489.1982 73
6{48} MeO MeO 3-MeO NMe2 [M]+ 463.1817 463.1826 72
6{49} MeO MeO 2-MeO piperidino [M+H]+ 503.2130 504.2209 99 77
6{50} MeO MeO 2-MeO morpholino 72
7{37}d OH OH 2-OH morpholino [M+H]+ 463.1453 464.1527 >99 17g
6{51} MeO MeO 2-MeO pyrrolidino 68
7{38}d OH OH 2-OH pyrrolidino ndi
6{52} MeO MeO 2-MeO NMe2 71
7{39}d OH OH 2-OH NMe2 ndi
6{53} OCH2O 4-MeO piperidino [M]+ 487.1817 487.1817 81
6{54} OCH2O 4-MeO morpholino [M+H]+ 489.1610 490.1692 >99 77h
6{55} OCH2O 4-MeO pyrrolidino [M+H]+ 473.1661 474.1754 98 69
6{56} OCH2O 4-MeO NMe2 79
6{57} OCH2O 2-MeO piperidino [M+H]+ 487.1817 488.1896 93 76
6{58} OCH2O 2-MeO morpholino 63h
6{59} OCH2O 2-MeO pyrrolidino 69h
6{60} OCH2O 2-MeO NMe2 [M]+ 447.1504 447.1512 76
a

Reagents and conditions: i. Mitsunobu Coupling: 5 (0.2 mmol), alkylaminoethanol (1.5 equiv), DIAD (1.5 equiv), PPh3 (2.0 equiv), THF (2.0 mL), rt, 24–36 h. ii. Demethylation: 6 (0.1mmol), BBr3, CH2Cl2 (1.0 mL), rt, N2, 3 h.

b

2.0 Equiv of BBr3 used.

c

4.0 Equiv of BBr3 used.

d

6.0 Equiv of BBr3 used.

e

UV purity determined at 214 nm after preparative HPLC.

f

Isolated yields after column chromatography. All isolated products were characterized by 1H and13C NMR spectroscopy (see the Supporting Information).

g

Isolated yield after preparative HPLC.

h

An inseparable mixture was obtained.

i

The final product was not purified, because of poor solubility.