121
(96), 209 (28), 192 (38), 181 (16), 167 (17), 154 (15), 127
(27), 71 (32), 43 (41), 42 (41). H-NMR (200 Mhz,
6.1.21. 8â-(3,5-Dioxopiperazin-1-ylmethyl)-1,6-dimethyl-
ergoline 21
1
Py-d5): δ 1.0–1.7 (m, 10 H, N-cyclohexyl hydrogen
H-2’ax, H-6’ax, CH2-3’, CH2-4’, CH2-5’), 2.14 (d, J =
11.9, 11.9 Hz, 1 H, H-7ax), 2.3–2.6 (m, 4 H, CH2-8,
N-cyclohexyl hydrogen H-2’e, H-6’e), 2.46 (s, 3 H,
CH3N), 2.89 (ddd, J = 1.5, 11.2, 14.2 Hz, 1 H, H-4ax),
3.0–3.2 (m, 2 H, H-7e, H-8ax), 3.23 (m, 1 H, H-5ax), 3.63
(dd, J = 5.3, 14.2 Hz, 1 H, H-4e), 3.65 (s, 4 H,
N(CH2CO)2), 4.72 (m, 1 H, N-cyclohexyl H-1’ax), 6.55
(bs, 1 H, H-9), 7.2–7.5 (m, 4 H, H-2, H-12, H-13, H-14),
11.69 (bs, 1 H, NH-1).
Compound 21 was synthesised from 2 following the
procedure reported for 20. MS m/z: 366 (C21H26N4O2,
43, [M]+ ), 251 (13), 239 (15), 237 (14), 194 (9), 181
(25), 168 (48), 158 (26), 127 (18), 44 (37), 42 (100).
1H-NMR (200 MHz, Py-d5): δ 0.93 (ddd, J = 12.2, 12.2,
12.2 Hz, 1 H, H9-ax), 1.81 (dd, J = 11.3, 11.3 Hz, 1 H,
H-7ax), 1.95 (dd, J = 4.3, 9.2 Hz, 1 H, H-8ax), 2.24 (ddd,
J = 4.5, 9.5, 11.6 Hz, 1 H, H-5ax), 2.14 (m, 1H, H-9ax),
2.34 (s, 3 H, CH3N), 2.3–2.4 (m, 2 H, H-4ax, H-9e), 2.61
(m, CH2-8), 2.77 (ddd, J = 3.5, 9.5, 12.3 Hz, 1 H,
H-10ax), 2.89 (bd, J = 11.3, 1 H, H-7e), 3.31 (dd, J = 4.3,
14.6 Hz, 1 H, H-4e), 3.35 (s, 4 H, N(CH2CO)2) 3.74 (s,
3 H, CH3-1), 6.87 (d, J = 7.8 Hz, 1 H, H-12), 6.96 (t, J =
7.8 Hz, 1 H, H-13), 7.15 (d, J = 7.8 Hz, 1 H, H-14), 11.25
(bs, 1 H, CONHCO).
6.1.19.
[8â-(3,5-dioxo-4-aminopiperazin-1-yl)-
methyl]-9,10-didehydro-6-methylergoline 19
Compound 19 was synthesised from N-(9,10-
didehydro-8â-ylmethyl-6-methylergoline)-iminodiacetic
acid diethyl ester and hydrazine hydrate following the
procedure reported for 1. MS m/z: 365 (C20H23N5O2, 76,
[M]+ ), 236 (17), 223 (95), 221 (100), 207 (26), 193 (70),
6.1.22. 8â-(3,5-Dioxopiperazin-1-ylmethyl)-6-propyl-
ergoline 22
1
Compound 22 was synthesised from 10 following the
procedure reported for 20. MS m/z: 380 (C22H28N4O2,
29, [M]+ ), 265 (9), 253 (14), 251 (9), 223 (22), 167 (30),
154 (59), 153 (41), 144 (30), 127 (58), 71 (37), 44 (41),
43 (74), 42 (100). 1H-NMR (200 MHz, Py-d5): δ 0.85 (t,
J = 7.3. Hz, 3 H, CH3CH2CH2N), 1.18 (ddd, J = 12.2,
180 (23), 167 (26), 154 (27), 42 (38). H-NMR (200
MHz, DMSO-d6): δ 2.08 (dd, J = 9.8, 10.7 Hz, 1 H,
H-7ax), 2.42 (s, 3 H, CH3N), 2.84 (m, 1 H, H-8ax), 3.43
(dd, J = 5.5, 14.6 Hz, 1 H, H-4e), 3.55 (s, 4 H,
N(CH2CO)2), 5.12 (bs, 2 H, N–NH2), 6.22 (bs, 1 H, H-9),
6.9–7.2 (m, 4 H, H-2, H-12, H-13, H-14).
12.2, 12.2 Hz,
1 H, H-9ax), 1.42 (m, 2 H,
CH3CH2CH2N), 2.02 (dd, J = 11.2, 11.2 Hz, 1 H, H-7ax),
2.20 (m, 2 H, H-5ax, H-8ax), 2.27 (ddd, J = 1.7, 11.4,
14.8 Hz, 1 H, H-4ax), 2.45 (m, 2 H, CH3CH2CH2N), 2.50
(m, 2 H, CH2-8), 2.60 (m, 1 H, H-9e), 2.95 (m, 2 H, H-7e,
H-10ax), 3.35 (s, 4 H, N(CH2CO)2), 6.71 (d, J = 8.0 Hz,
1 H, H-12), 6.93 (t, J = 8.0 Hz, 1 H, H-13), 7.15 (d, J =
8.0 Hz, 1 H, H-14), 10.63 (bs, 1H, NH-1), 11.27 (bs, 1 H,
CONHCO).
6.1.20. 8â-(3,5-Dioxopiperazin-1-ylmethyl)-6-methyl-
ergoline 20
A solution of 1 (7 g, 20 mmol) in acetic acid (170 mL)
was hydrogenated at 3 atmosphere pressure over 2.5 g of
10% Pd/C. The calculated amount of H2 was taken up in
3 h. The catalyst was removed by filtration and the
solvent was evaporated off. The residue dissolved in
chloroform, was washed with dilute ammonium hy-
droxyde solution, then the organic phase was dried and
evaporated. The residue was crystallised from acetone to
afford 5.3 g of 20 (75% yield). MS m/z: 352
(C20H24N4O2, 93, [M]+ ), 237 (40), 225 (46), 223 (39),
207 (24), 194 (39), 167 (69), 154 (100), 144 (61), 127
(60), 44 (46), 42 (68). 1H-NMR (200 MHz, DMSO-d6): δ
0.96 (ddd, J = 12.3, 12.3, 12.3 Hz, 1 H, H9-ax), 1.79 (dd,
J = 11.4, 11.4 Hz, 1 H, H-7ax), 1.93 (dd, J = 4.3, 9.2 Hz,
1 H, H-8ax), 2.23 (ddd, J = 4.3, 9.5, 11.5 Hz, 1 H, H-5ax),
2.10 (m, 1H, H-9ax), 2.32 (s, 3 H, CH3N), 2.3–2.36 (m,
2 H, H-4ax, H-9e), 2.59 (m, CH2-8), 2.75 (ddd, J = 3.5,
9.5, 12.3 Hz, 1 H, H-10ax), 2.88 (bd, J = 11.4, 1 H, H-7e),
3.28 (dd, J = 4.3, 14.6 Hz, 1 H, H-4e), 3.38 (s, 4 H,
N(CH2CO)2), 6.77 (d, J = 8.0 Hz, 1 H, H-12), 6.99 (t, J
= 8.0 Hz, 1 H, H-13), 7.10 (d, J = 8.0 Hz, 1 H, H-14),
10.59 (bs, 1H, NH-1), 11.20 (bs, 1 H, CONHCO).
6.1.23.
[8â-(3,5-dioxo-4-methylpiperazin-1-yl)-
methyl]-6-methylergoline 23
Compound 23 was synthesised from 15 following the
procedure reported for 20.
MS m/z: 366 (C21H26N4O2, 100, [M]+ ), 237 (31), 225
(31), 223 (22), 167 (37), 154 (37), 144 (20), 141 (13), 127
1
(13), 44 (19), 42 (26). δ H-NMR (200 MHz, Py-d5): δ
0.98 (ddd, J = 12.2, 12.2, 12.2 Hz, 1 H, H9-ax), 1.76 (dd,
J = 11.4, 11.4 Hz, 1 H, H-7ax), 1.94 (dd, J = 4.2, 9.2 Hz,
1 H, H-8ax), 2.24 (ddd, J = 4.2, 9.5, 11.5 Hz, 1 H, H-5ax),
2.12 (m, 1H, H-9ax), 2.32 (s, 3 H, CH3N), 2.3–2.4 (m, 2
H, H-4ax, H-9e), 2.58 (m, CH2-8), 2.77 (ddd, J = 3.5, 9.5,
12.2 Hz, 1 H, H-10ax), 2.88 (bd, J = 11.4, 1 H, H-7e),
3.15 (s, 3 H, CON(CH3)CO), 3.28 (dd, J = 4.2, 14.6 Hz,
1 H, H-4e), 3.38 (s, 4 H, N(CH2CO)2), 6.77 (d, J = 8.0