10.1002/cmdc.201600626
ChemMedChem
FULL PAPER
MHz, CDCl3): δ=12.72, 13.51, 15.44, 16.56, 19.55, 21.44, 21.92,
24.55, 26.23, 26.47, 28.80, 30.25, 32.70, 33.96, 34.26, 36.26,
36.72, 37.14, 38.61, 39.31, 40.60, 40.70, 41.48, 44.98, 46.77,
49.69, 52.93, 71.27, 87.90, 112.48, 143.17, 153.11, 166.19 ppm;
IR (film): ν=2925, 2865, 1535 (thiazole), 1468 (thiazole), 1035 cm-
1; MS (ESI) m/z (%): 553.4 (100) [M+H]+; Anal. calcd for
C35H56N2OS: C 76.03, H 10.21, N 5.07, S 5.80; found C 75.54, H
10.36, N 4.64, S 5.57.
benzylammonium acetate (836 mg; 5.0 mmol) in chloroform (20
mL) after 24 hours controlled by TLC (mobile phase
toluene/diethylether 5:1). Dissolved crude product was filtered
through a short pad of silica gel. Evaporation of solvent furnished
2i (522 mg; 89 %): Rf=0.10 (toluene/diethylether 5:1); mp: 148–
1
154 °C (toluene/diethylether); [α]D20=+56 (c=0.61 in CHCl3); H
NMR (300 MHz, CDCl3): δ=0.81 (s, 3H), 0.92 (s, 3H), 0.95 (s, 6H),
1.03 (s, 3H), 1.14 (s, 3H), 1.24 (s, 3H, 7×CH3), 2.15 (d, J = 15.5
Hz, 1H, H-1a), 2.59 (d, J = 15.2 Hz, 1h, H-1b), 3.46 (d, J = 7.9 Hz,
1H, H-28a), 3.55 (s, 1H, H-19), 3.80 (d, J = 7.9 Hz, 1H, H-28b),
4.39 (s, 2H, PhCH2), 5.59 (bs, 1H, NH), 7.29 – 7.44 ppm (m, 5H,
Ph); 13C NMR (75 MHz, CDCl3): δ=13.49, 15.43, 16.51, 19.45,
21.45, 21.99, 24.55, 26.22, 26.43, 26.47, 28.80, 30.23, 32.69,
33.00, 34.25, 36.26, 36.71, 37.00, 38.66, 39.28, 40.60, 40.71,
41.48, 46.75, 49.68, 50.13, 52.80, 71.25, 87.89, 114.31, 127.63,
127.72, 128.62, 137.71, 142.82, 151.94, 166.77 ppm; IR (film):
ν=3520 (NH), 2934, 2865, 1542 (thiazole), 1463 (thiazole), 1035
cm-1; MS (ESI) m/z (%): 587.4 (100) [M+H]+; Anal. calcd for
C38H54N2OS: C 77.76, H 9.27, N 4.77, S 5.46; found C 77.69, H
9.28, N 4.55, S 4.93.
Thiazole derivative 2g
Compound 2g was prepared according to the general procedure
from 2/-thiocyano allobetulone (2c) (500 mg; 1.0 mmol) and
dibutylammonium acetate (947 mg; 5.0 mmol) in chloroform (20
mL) after 24 hours controlled by TLC (mobile phase
toluene/diethylether 5:1). Dissolved crude product was filtered
through a short pad of silica gel. Evaporation of solvent furnished
2g (463 mg; 76 %): Rf=0.40 (toluene/diethylether 5:1); mp: 148–
1
152 °C (toluene/diethylether); [α]D20=+55 (c=0.51 in CHCl3); H
NMR (300 MHz, CDCl3): δ=0.81 (s, 3H), 0.92 – 0.97 (m, 15 H),
1.03 (s, 3H), 1.11 (s, 3H), 1.21 (s, 3H, 7×CH3,
(CH3CH2CH2CH2)2N), 1.28 -1.40 (m, 8H, (CH3CH2CH2CH2)2N),
2.13 (d, J = 15.2 Hz, 1H, H-1a), 2.58 (d, J = 15.0 Hz, 1H, H-1b),
3.24 – 3.43 (m, 4H, (CH3CH2CH2CH2)2N), 3.46 (d, J = 7.6 Hz, 1H,
H-28a), 3.55 (s, 1H, H-19), 3.80 ppm (d, J = 7.6 Hz, 1H, H-28b);
13C NMR (75 MHz, CDCl3): δ=13.51, 13.92, 15.44, 16.58, 19.55,
20.16, 21.42, 21.92, 24.55, 26.23, 26.48, 27.41, 28.80, 29.62,
30.23, 32.70, 33.07, 34.26, 36.26, 36.72, 37.14, 38.61, 39.31,
40.60, 40.70, 41.48, 46.77, 49.69, 50.81, 52.89, 71.28, 87.90,
112.27, 143.78, 153.01, 166.74 ppm; IR (film): ν=2925, 2864,
1538 (thiazole), 1465 (thiazole), 1035 cm-1; MS (ESI) m/z (%):
Thiazole derivative 2j
Compound 2j was prepared according to the general procedure
from 2/-thiocyano allobetulone (2c) (500 mg; 1.0 mmol) and
morpholinium acetate (736 mg; 5.0 mmol) in chloroform (20 mL)
after 24 hours controlled by TLC (mobile phase
toluene/diethylether 5:1). Dissolved crude product was filtered
through a short pad of silica gel. Evaporation of solvent furnished
2j (510 mg; 90 %): Rf=0.20 (toluene/diethylether5:1); mp: 151–
1
155 °C (toluene/diethylether); [α]D20=+65 (c=0.95 in CHCl3); H
609.4 (100) [M+H]+; Anal. calcd for C39H64N2OS: C 76.92, H 10.59, NMR (500 MHz, CDCl3): δ=0.81 (s, 3H), 0.91 (s, 3H), 0.95 (s, 6H),
N 4.60, S 5.27; found C 76.92, H 10.61, N 4.33, S 5.24.
1.03 (s, 3H), 1.12 (s, 3H), 1.22 (s, 3H, 7×CH3), 2.17 (d, J = 15.2
Hz, 1H, H-1a), 2.63 (d, J = 15.2 Hz, 1H, H-1b), 3.39 (t, J = 4.9 Hz,
4H, O(CH2CH2)2N), 3.46 (d, J = 8.1 Hz, 1H, H-28a), 3.55 (s, 1H,
H-19), 3.79 – 3.81 ppm (m, 5H, H-28b, O(CH2CH2)2N); 13C NMR
(75 MHz, CDCl3): δ=13.49, 15.43, 16.49, 19.52, 21.47, 21.98,
24.55, 26.23, 26.45, 26.47, 28.79, 30.29, 32.71, 33.04, 34.27,
36.27, 36.73, 37.22, 38.63, 39.30, 40.62, 40.72, 41.49, 46.78,
48.57, 49.69, 52.89, 66.28, 71.27, 87.90, 115.21, 153.34, 168.39
ppm; IR (film): ν=2924, 2856, 1529 (thiazole), 1452 (thiazole),
1036 cm-1; MS (ESI) m/z (%): 567.4 (100) [M+H]+; Anal. calcd for
C35H54N2O2S: C 74.16, H 9.60, N 4.94, S 5.66; found C 73.43, H
9.63, N 4.59, S 6.03.
Thiazole derivative 2h
Compound 2h was prepared according to the general procedure
from 2/-thiocyano allobetulone (2c) (500 mg; 1.0 mmol) and
dioctylammonium acetate (1.50 g; 5.0 mmol) in chloroform (20
mL) after 24 hours controlled by TLC (mobile phase
toluene/diethylether 5:1). Dissolved crude product was filtered
through a short pad of silica gel. Evaporation of solvent furnished
2h (562 mg; 78 %): Rf=0.45 (toluene/diethylether 5:1); mp: 146–
152 °C (toluene/diethylether); [α]D20=+51 (c=1.18 in CHCl3); H
1
NMR (300 MHz, CDCl3): δ=0.81 (s, 3H), 0.86 – 0.91 (m, 6H, H-
dioctyl), 0.93 (s, 3H), 0.95 (s, 6H), 1.03 (s, 3H), 1.11 (s, 3H), 1.22
(s, 3H, 7×CH3), 1.25 – 1.33 (m, 24H, (CH3(CH2)6CH2)2N), 2.14 (d,
J = 15.2 Hz, 1H, H-1a), 2.59 (d, J = 14.9 Hz, 1H, H-1b), 3.23 –
3.41 (m, 4H, (CH3(CH2)6CH2)2N), 3.46 (d, J = 7.9 Hz, 1H, H-28a),
3.56 (s, 1H, H-19), 3.81 ppm (d, J = 7.9 Hz, 1H, H-28b); 13C NMR
(75 MHz, CDCl3): δ=13.52, 14.11, 15.44, 16.58, 19.57, 21.43,
21.93, 22.65, 24.55, 26.24, 26.49, 26.98, 27.42, 27.46, 28.80,
29.24, 29.34, 30.25, 31.82, 32.70, 33.08, 34.27, 36.27, 36.73,
37.15, 38.62, 39.33, 40.61, 40.71, 41.49, 46.78, 49.70, 51.19,
52.90, 71.28, 87.91, 112.27, 143.09, 153.02, 166.72 ppm; IR
(film): ν=2925, 2856, 1539 (thiazole), 1453 (thiazole), 1036 cm-1;
MS (ESI) m/z (%): 721.6 (100) [M+H]+; Anal. calcd for
C47H80N2OS: C 78.27, H 11.18, N 3.88, S 4.45; found C 77.65, H
11.09, N 3.53, S 4.43.
Thiazole derivative 2k
Compound 2k was prepared according to the general procedure
from 2/-thiocyano allobetulone (2c) (500 mg; 1.0 mmol) and N-
methylpiperazinium acetate (802 mg; 5.0 mmol) in chloroform (20
mL) after 24 hours controlled by TLC (mobile phase
toluene/diethylether 5:1). Dissolved crude product was filtered
through a short pad of silica gel. Evaporation of solvent furnished
2k (557 mg; 96 %): Rf=0.15 (toluene/diethylether 5:1); mp: 147–
154 °C (toluene/diethylether); [α]D20=+61 (c=0.99, CHCl3); 1H
NMR (300 MHz, CDCl3): δ=0.80 (s, 3H), 0.90 (s, 3H), 0.94 (s, 6H),
1.02 (s, 3H), 1.11 (s, 3H), 1.21 (s, 3H, 7×CH3), 2.15 (d, J = 15.2
Hz, 1H, H-1a), 2.35 (s, 3H, N-CH3), 2.52 – 2.55 (m, 4H,
CH3N(CH2CH2)2N), 2.61 (d, J = 15.2 Hz, 1H, H-1b), 3.40 – 3.48
(m, 5H, H-28a, CH3N(CH2CH2)2N), 3.54 (s, 1H, H-19), 3.79 ppm
(d, J = 7.6 Hz, 1H, H-28b); 13C NMR (75 MHz, CDCl3): δ=13.50,
15.42, 16.51, 19.51, 21.45, 21.98, 24.55, 26.22, 26.44, 28.79,
30.28, 32.69, 33.03, 34.25, 36.26, 36.71, 37.19, 38.59, 39.28,
Thiazole derivative 2i
Compound 2i was prepared according to the general procedure
from 2/-thiocyano allobetulone (2c) (500 mg; 1.0 mmol) and
8
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