2-(2-Furanyl)pyrazine 10c. Prepared by the procedure given
for 6a using 1-(2-furanyl)-2-hydroxyethanone 1d12 (0.50 mmol,
0.064 g) and ethylenediamine 5a (1.00 mmol, 0.07 mL). Column
chromatography (2 : 1 PE : EtOAc) gave the title compound 10c
(0.044 g, 60%) as a yellow oil: Rf 0.67 (2 : 1 PE : EtOAc); νmax
(film) 1590, 1470, 1411, 1384 cmϪ1; δH (270 MHz) 6.57 (1 H, m,
H-4Ј), 7.15 (1 H, m, H-3Ј), 7.60 (1 H, m, H-5Ј), 8.42 (1 H, d,
J 2.7 Hz, H-6), 8.53 (1 H, d, J 2.7 Hz, H-5), 8.97 (1 H, s, H-3); δC
(100 MHz) 111.3, 112.9, 138.3, 141.2, 143.1, 144.7, 145.0, 147.9;
m/z (CI) 147 (MHϩ) [HRMS (CI) calcd. for C8H7N2O 147.0558.
Found 147.0558 (0.0 ppm error)].
140.5, 141.2, 143.9, 157.0, 172.7, 199.8; m/z (CI) 433 (MHϩ),
415 (MHϩ Ϫ H2O) [HRMS (CI) calcd. for C27H33N2O3
433.2491. Found 433.2497 (1.3 ppm error)].
17-(5,6-Dihydropyrazin-2-yl)-11,17-dihydroxy-10,13-dimethyl-
1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydrocyclopenta-
[a]phenanthren-3-one 13
Prepared by the procedure given for 6a using hydrocortisone 1i
(0.20 mmol, 0.072 g) and ethylenediamine 5a (0.40 mmol, 0.027
mL). Purified by column chromatography (25 : 1 to 15 : 1
CH2Cl2 : MeOH) to give the title compound 13 (0.030 g, 40%) as
the only isolated product, a pale yellow solid: Rf 0.24 (9 : 1
CH2Cl2 : MeOH); mp 130–132 ЊC; νmax (nujol) 3404, 1659, 1615,
1590, 1276, 1233, 1189, 1119, 950, 926, 868 cmϪ1; δH (400 MHz)
0.96 (3 H, s, CH3), 1.01–1.04 (1 H, m), 1.06–1.21 (1 H, m), 1.42
(3 H, s, CH3), 1.34–1.52 (3 H, m), 1.54–1.65 (1 H, m), 1.71–1.95
(3 H, m), 1.96–2.09 (3 H, m), 2.12–2.28 (2 H, m), 2.33 (1 H, m),
2.39–2.53 (2 H, m), 2.73 (1 H, m), 3.34–3.55 (4 H, m, DHP),
2-Phenyl-5,6,7,8-tetrahydoquinoxaline 10d. Prepared by the
procedure given for 6a using α-hydroxyacetophenone 1c (0.50
mmol, 0.068 g) and trans-1,2-diaminocyclohexane 5b (0.60
mmol, 0.07 mL). With trans-1,2-diaminocyclohexane 5b no
HCl was used. Column chromatography (3 : 1 PE : EtOAc) gave
the title compound 10d (0.069 g, 66%) as a colourless oil: Rf 0.31
(2 : 1 PE : EtOAc); νmax (film) 2937, 2861, 1457, 1444, 1380,
1142, 775, 694 cmϪ1; δH (270 MHz) 1.78–1.94 (4 H, m, H-6,7),
2.83–2.98 (4 H, m, H-5,8), 7.29–7.43 (3 H, m, H-3Ј,4Ј,5Ј), 7.82–
7.91 (2 H, m, H-1Ј,6Ј), 8.64 (1 H, s, H-3); δC (68 MHz) 22.7,
22.7, 31.8, 32.8, 126.8, 129.0, 129.3, 137.0, 138.9, 149.8, 151.3,
152.4; m/z (CI) 211 (MHϩ) [HRMS (CI) calcd. for C14H15N2
211.1235. Found 211.1234 (0.7 ppm error)].
3.87 (1 H, br s, OH), 4.43 (1 H, br s, OH), 5.66 (1 H, s, C᎐CH),
᎐
8.11 (1 H, d, J 1.5 Hz, imine); δC (100 MHz) 18.5, 21.1, 24.2,
31.5, 32.2, 32.8, 33.5, 33.9, 35.1, 39.3, 39.9, 43.9, 44.5, 48.5,
51.7, 56.1, 68.5, 84.7, 122.4, 152.6, 162.2, 172.4, 199.7; m/z (CI)
385 (MHϩ) [HRMS (CI) calcd. for C23H33N2O3 385.2491.
Found 385.2489 (0.5 ppm error)].
17-(4a,5,6,7,8,8a-Hexahydroquinoxalin-2-yl)-11,17-dihydroxy-
10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradeca-
hydrocyclopenta[a]phenanthren-3-one 14
2-(2-Furanyl)-5,6,7,8-tetrahydoquinoxaline 10e. Prepared by
the procedure given for 6a using α-hydroxyacetophenone 1c
(0.50 mmol, 0.068 g) and trans-1,2-diaminocyclohexane 5b
(0.60 mmol, 0.07 mL). With trans-1,2-diaminocyclohexane 5b
no HCl was used. Column chromatography (3 : 1 PE : EtOAc)
gave the title compound 10e (0.069 g, 66%) as a colourless oil: Rf
0.31 (2 : 1 PE : EtOAc); νmax (film) 2937, 2861, 1457, 1444, 1380,
1142, 775, 694 cmϪ1; δH (270 MHz) 1.78–1.94 (4 H, m, H-6,7),
2.83–2.98 (4 H, m, H-5,8), 7.29–7.43 (3 H, m, H-3Ј,4Ј,5Ј),
7.82–7.91 (2 H, m, H-1Ј,6Ј), 8.64 (1 H, s, H-3); δC (68 MHz)
22.7, 22.7, 31.8, 32.8, 126.8, 129.0, 129.3, 137.0, 138.9, 149.8,
151.3, 152.4; m/z (CI) 211 (MHϩ) [HRMS (CI) calcd. for
C14H15N2 211.1235. Found 211.1234 (0.7 ppm error)].
Prepared by the procedure given for 6a using hydrocortisone 1i
(0.20 mmol, 0.072 g) and trans-1,2-diaminocyclohexane 5b
(0.24 mmol, 0.028 mL). Purified by column chromatography
(EtOAc to 19 : 1 EtOAc : MeOH) to give the title compound
14 (0.072 g, 82%) as an inseparable mixture of diastereomers
(∼1 : 1 A : B), a colourless solid: Rf 0.19 (EtOAc); mp 123–
125 ЊC; νmax (nujol) 3393, 1658, 1615, 1584, 1233, 1118, 915, 730
cmϪ1; δH (400 MHz) 0.88 (3 H, s, CH3A), 0.93 (3 H, s, CH3B),
0.94–1.00 (1 H, m, A ϩ B), 1.02–1.18 (1 H, m, A ϩ B), 1.24–
1.57 (6 H, m, A ϩ B), 1.39 (3 H, s, CH3A ϩ B), 1.60–2.06 (11 H,
m, A ϩ B), 2.08–2.82 (10 H, m, A ϩ B), 3.68 (1 H, br s, OH, A),
4.39 (1 H, br s, OH, A ϩ B), 4.52 (1 H, br s, OH, B), 5.62 (1 H, s,
2-Cyclohexylpyrazine 10f. Prepared by the procedure given
for 6a using 1-cyclohexyl-2-hydroxyethanone 1b13 (0.50 mmol,
0.106 g) and ethylenediamine 5a (1.00 mmol, 0.07 mL). Column
chromatography (3 : 1 PE : EtOAc) gave the title compound 10f
(0.027 g, 33%) as a yellow oil: Rf 0.38 (3 : 1 PE : EtOAc); νmax
(film) 1558, 1441, 1381 cmϪ1; δH (400 MHz) 1.32–1.94 (10 H, m,
H-2Ј,3Ј,4Ј,5Ј,6Ј), 2.75 (1 H, dd, J 11.9 Hz, J 2.4 Hz, H-1Ј), 8.37
(1 H, s, H-3), 8.39 (2 H, m, H-5,6); δC (100 MHz) 25.8, 26.3,
32.4, 44.0, 142.2, 143.6, 143.9, 161.0; m/z (EI) 162 (Mϩ) [HRMS
(EI) calcd. for C10H14N2 162.1157. Found 162.1156 (0.8 ppm
error)].
C᎐CH A ϩ B), 7.98 (1 H, d, J 2.8 Hz, imine A), 8.04 (1 H, d,
᎐
J 2.7 Hz, imine B); δC (100 MHz) 18.4/18.5 (CH3), 21.0/21.1
(CH3), 24.0/24.3 (CH2), 25.4/25.5 (CH2), 25.5/25.5 (CH2), 31.4/
31.5 (CH), 32.2 (CH2), 32.7/32.8 (CH2), 32.9/33.7 (CH2), 33.0/
33.1 (CH2), 33.5/33.5 (CH2), 33.8 (CH2), 34.9 (CH2), 39.2/39.3
(C), 39.5/40.0 (CH2), 48.0/48.9 (C), 51.5/51.6 (CH), 56.1/56.1
(CH), 58.1/58.3 (CH), 58.8/59.1 (CH), 68.2/68.3 (CH), 84.1/84.5
(C), 122.2/122.3 (CH), 151.5/152.4 (CH), 161.7/161.8 (C),
172.6/172.7 (C), 199.7/199.7 (C) [The pairs of signals were
tentatively assigned due to their similar chemical shift and type;
however, this is by no means a definitive assignation]; m/z (CI)
439 (MHϩ) [HRMS (CI) calcd. for C27H39N2O3 439.2961.
Found 439.2967 (1.4 ppm error)].
11,17-Dihydroxy-10,13-dimethyl-17-quinoxalin-2-yl-
1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydocyclopenta-
[a]phenanthren-3-one 12
11,17-Dihydroxy-10,13-dimethyl-17-piperazin-2-yl-1,2,6,7,8,9,-
10,11,12,13,14,15,16,17-tetradecahydocyclopenta[a]phenan-
thren-3-one 15
Prepared by the procedure given for 4a using hydrocortisone 1i
(0.20 mmol, 0.072 g) and o-phenylenediamine 2a (0.40 mmol,
0.043 g). Purified by column chromatography (EtOAc) to give
the title compound 12 (0.058 g, 67%) as an orange solid: Rf 0.50
(EtOAc); mp 266–268 ЊC; νmax (nujol) 3392, 1638, 1276, 1231,
1227, 1112, 942, 865, 775 cmϪ1; δH (400 MHz) 0.86 (3 H, s,
CH3), 1.01 (1 H, dd, J 10.7 Hz, J 3.1 Hz), 1.08–1.18 (1 H, m),
1.31 (1 H, dd, J 14.0 Hz, J 2.1 Hz), 1.37 (3 H, s, CH3), 1.50–1.64
(1 H, m), 1.77 (1 H, dt, J 4.6 Hz, J 13.4 Hz), 1.86–2.51 (12 H,
m), 3.04 (1 H, dd, J 12.5 Hz, J 11.9 Hz), 4.41 (1 H, s, OH), 4.61
Prepared by the procedure given for 9a using hydrocortisone 1g
(0.20 mmol, 0.072 g) and ethylenediamine 5a (0.40 mmol, 0.027
mL). Acid/base extraction gave the title compound 15 (0.054 g,
69%) as a colourless solid: mp 104–106 ЊC; νmax (CH2Cl2) 3445,
3053, 2934, 1661, 1451, 1266, 1133, 909, 738, 704 cmϪ1; δH (400
MHz) 0.73–3.16 (28 H, m), 1.02 (3 H, s, CH3), 1.40 (3 H, s,
CH ), 4.33 (1 H, br s, OH), 5.63 (1 H, s, C᎐CH); δ (100 MHz)
᎐
3
C
(1 H, s, OH), 5.61 (1 H, s, C᎐CH), 7.67–7.76 (2 H, m, H-6,7),
16.9, 21.1, 23.4, 31.3, 32.3, 32.7, 33.9, 35.0, 37.3, 39.3, 41.5,
45.5, 45.8, 46.6, 46.9, 52.1, 56.0, 61.5, 68.2, 83.6, 122.2, 173.0,
199.9; m/z (CI) 389 (MHϩ) [HRMS (CI) calcd. for C23H37N2O3
389.2804. Found 389.2807 (0.8 ppm error)].
᎐
7.96–8.07 (2 H, m, H-5,8), 9.01 (1 H, s, H-3); δC (100 MHz)
18.5, 21.0, 24.3, 31.9, 32.2, 32.8, 33.8, 34.9, 35.0, 39.3, 39.4,
49.1, 51.9, 56.1, 68.4, 84.8, 122.3, 129.0, 129.1, 129.8, 130.3,
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 8 8 – 7 9 6
795