S. Bellemin-Laponnaz, G. Guichard et al.
Compound 14: A solution of 8 (15 mg, 0.023 mmol) in THF (1 mL)
5.26 (m, 1H; CHFmoc), 5.79 (s, 2H; Nimidazole-CH ), 6.78 (s, 1H;
2
and a solution of H C-(OCH CH ) -N (18 mg, 0.050 mmol) in THF
CHimidazole), 7.19–7.78 (br, 17H; 13Ar-H, CH
and 3CHpyridine),
triazole
3
2
2 6-7
3
13
(
1 mL) were added to a solution of [RuClCp*(PPh ) ] (1.4 mg,
9.04 ppm (d, 2H; CHpyridine); C NMR (CDCl , 75 MHz, 208C): d=
3
2
3
1
.840 mmol) in THF (0.5 mL). The mixture was then heated 30 min
22.3, 29.4, 32.0, 36.3 (Nimidazole-CH ), 47.2, 48.4, 52.6, 53.5, 55.1
3
at 658C. The solvent was then removed under vacuum. The residue
(Nimidazole-CH ), 67.1, 120.0, 121.5, 125.1, 127.1, 127.7, 128.8, 129.1,
2
was purified by means of silica gel chromatography using dichloro-
129.3, 134.7, 135.7, 137.6, 141.3, 143.8, 153.7 (CHpyridine), 155.9
methane/methanol 10:0.7 to afford compound 14 as a yellow-
(NHCO ), 172.5 ppm (CO ); HRMS (positive ESI): m/z calcd for
2
2
1
brown oil (23 mg, 72%). H NMR (CDCl , 300 MHz, 208C): d=3.34–
C H IN O Pt: 1005.191 [MÀI]; found: 1005.194.
3
40 41
7
4
3
.99 (br, 60–64H; 2O-CH , 14CH and 2N-CH ), 4.31 (br, 4H; Ntriazole-
3
2
3
Compound 18: A solution of 9 (80 mg, 0.100 mmol) in THF (5 mL)
CH ), 5.65 (s, 2H; N
-CH ), 5.81 (s, 2H; N
-CH ), 7.22–7.56
imidazole 2
2
imidazole
2
[37]
and a solution of N -l-Phe-OBn
(31 mg, 0.110 mmol) in THF
3
(
br, 12H; Ar-H), 7.76 (s, 1H; CHtriazole), 7.79 ppm (s, 1H; CHtriazole);
1
3
(5 mL) were added to a solution of [RuClCp*(PPh ) ] (7 mg,
3
2
C NMR (CDCl , 75 MHz, 208C): d=36.2 (N-CH ), 36.3 (N-CH ), 48.4
3
3
3
0
7
.008 mmol) in THF (5 mL). The mixture was then heated for 2 h at
08C. The solvent was then removed under vacuum. The residue
(
2CH ), 54.8 (N
-CH ), 54.9 (N
-CH ), 59.0 (2OCH ), 69.7,
imidazole 2 3
2
imidazole
2
7
1
0.0, 70.2, 70.6, 71.3, 120.9, 123.6, 126.2, 128.3, 128.4, 128.5, 128.7,
28.8, 128.9, 129.0, 132.0, 132.1, 134.8, 135.6, 172.3 ppm (C-Pd);
was purified by means of silica gel chromatography using dichloro-
methane to afford complex 18 as a yellow-brown oil (37 mg, 37%).
MALDI: m/z: found: 1308.104 [MÀBr].
1
H NMR (CDCl , 300 MHz, 208C): d=3.20 (s, 3H; N-CH ), 3.65 (m,
3
3
Compound 15: A solution of [RuClCp*(PPh ) ] (0.5 mg, 0.680 mmol)
2H; CH ), 4.79 (d, J=11.6, 4.3 Hz, 1H; CH), 5.14 (d, J=21.4, 12.2 Hz,
3
2
2
in THF (0.2 mL) and a solution of benzyl azide (7 mg, 0.053 mmol)
2H; O-CH ), 5.54 (s, 1H; CHimidazol), 5.72 (m, 2H; Nimidazol-CH ), 6.78
2
2
in THF (0.5 mL) were added to a solution of alkyne derivative 9
(m, 2H; 2Ar-H), 6.98–7.49 (m, 15H; 13Ar-H and 2CHpyridine), 7.67 (s,
(
13 mg, 0.015 mmol) in THF (1 mL). The mixture was then heated
1H; CHtriazole), 7.74 (tt, J=7.8, 1.5 Hz, 1H; CHpyridine), 9.02 ppm (m,
2H; 2CHpyridine); C NMR (CDCl , 75 MHz, 208C): d=35.6 (CH ), 37.2
3 3
13
for 2 h at 708C. The solvent was then removed under vacuum. The
residue was purified by means of silica gel chromatography using
a mixture of dichloromethane and cyclohexane 1:1 followed by
(CH ), 55.0 (N
-CH ), 62.2 (CH), 68.4 (OCH ), 119.2, 122.1, 124.9,
2 2
2
imidazol
125.0 (CHpyridine), 126.4, 127.1, 128.2, 128.3, 128.8, 128.9, 129.0,
129.2, 134.4, 134.7, 135.1, 135.5, 135.5, 137.6 (CHpyridine), 141.0 (C-
Pt), 153.7 (CHpyridine), 166.8 ppm (C=O); MS (positive ESI): m/z calcd
for C H I N O PtH: 1006.04 [M+H]; found: 1006.02.
ethyl acetate to afford compound 15 as a yellow-brown oil (12 mg,
1
8
2
7
9
2%). H NMR (CDCl , 300 MHz, 208C): d=3.57 (s, 3H; CH ), 5.37 (s,
3
3
H; Ntriazole-CH ), 5.73 (s, 2H; N
-CH ), 6.43 (s, 1H; CHimidazole),
2
imidazole
2
34 32 2
6
2
.19–7.51 (br, 13H; 10Ar-H and 3CHpyridine), 7.81 (s, 1H; CHtriazole),
13
Compound 21: Compound 20 obtained as reported in the litera-
.04 ppm (d, 2H; CHpyridine); C NMR (CDCl , 75 MHz, 208C): d=36.1
3
[31]
ture (160 mg, 0.324 mmol) was dissolved in methanol (10 mL),
and sodium azide (105 mg, 1.62 mmol) was added to this solution.
The solution was placed at reflux for 20 h under stirring. The sol-
vent was evaporated and diethyl ether (100 mL) was added to the
residue. The ethereal solution was washed with water (3ꢃ50 mL),
dried over anhydrous sodium sulphate, filtered and concentrated
(
1
1
CH ), 52.7 (N
-CH ), 55.2 (N
-CH ), 120.1, 121.6, 124.4,
3
triazole
2
imidazole 2
25.1, 125.3, 127.8, 128.7, 128.8, 129.1, 129.3, 129.5, 134.1, 134.6,
36.4, 137.7, 153.8 ppm; HRMS (positive ESI): m/z calcd for
C H IN Pt: 730.075 [MÀI]; found: 730.085.
2
5
24
6
Compound 16:
0
0
A
solution of alkyne derivative 10 (45 mg,
.060 mmol) in THF (3 mL) and a solution of benzyl azide (24 mg,
.181 mmol) in THF (4 mL) were added to a solution of [RuClCp*-
1
to afford product 21 as a white solid (104 mg, 71%). H NMR
(CDCl , 300 MHz, 208C): d=0.87 (s, 3H; CH3 oestrogen), 0.98–2.00 (m,
3
(
PPh ) ] (2.0 mg, 2.418 mmol) in THF (3 mL). The mixture was then
26H; 2CH and 12CH2 oestrogen), 2.69–2.83 (m, 3H; CH and CHoestrogen),
3
2
2
heated for 20 h at 708C. The solvent was then removed under
vacuum. The residue was purified by means of silica gel chroma-
tography using a mixture of ethyl acetate and cyclohexane 1:2 to
3.24–3.54 (m, 3H; CHOH and CH OHoestrogen), 3.80 (brd, 1H; OH),
2
4.78 (brs, 1H; OH), 6.57 (d, J=2.7 Hz, 1H; Ar-Hoestrogen), 6.63 (dd,
J =8.4 Hz, J =2.7 Hz, 1H; 1Ar-Hoestrogen), 7.15 ppm (d, J=8.7 Hz,
1
2
1
13
afford compound 10 as a yellow-brown oil (37 mg, 70%). H NMR
1H; 1Ar-Hoestrogen); C NMR (CDCl , 75 MHz, 208C): d=11.9 (CH
3 3 oes-
(
(
CDCl , 300 MHz, 208C): d=1.10–1.85 (br, 8H; CH2 cyclohexylamine), 2.30
m, 2H; CH2 cyclohexylamine), 3.00 (br, 2H; NH2), 3.29 (m, 1H;
trogen), 22.7, 24.8, 26.2, 27.4, 28.8, 29.5, 30.4, 31.9, 33.2, 38.0, 39.3,
3
43.9, 44.9, 47.0, 47.7, 49.2, 51.5, 67.0 (CH OHoestrogen), 90.7 (CHO-
2
CHcyclohexylamine), 3.47 (s, 3H; CH ), 5.35 (s, 2H; Ntriazole-CH ), 5.59 (s,
Hoestrogen), 112.7 (CHarom), 115.3 (CHarom), 126.4 (CHarom), 132.5 (CHarom),
138.1 (CHarom), 153.5 ppm (COHarom); HRMS (positive ESI): m/z calcd
for C H N O Na: 478.304 [M+Na]; found: 478.307.
3
2
2
7
7
H; Nimidazole-CH ), 6.38 (s, 1H; CH
.46 (br, 8H; 8Ar-H), 7.77 ppm (s, 1H; CHtriazole); C NMR (CDCl3,
), 7.01 (m, 2H; 2Ar-H), 7.25–
imidazole
2
13
27
41
3
3
5 MHz, 208C): d=24.8 (CH ), 25.3 (CH ), 35.9 (CH ), 36.0 (CH ), 52.7
2
2
3
2
Compound 22: A solution of 9 (43 mg, 0.059 mmol) in THF (4 mL)
and a solution of 21 (27 mg, 0.059 mmol) in THF (4 mL) were
added to a solution of [RuClCp*(PPh ) ] (2.8 mg, 3.516 mmol) in THF
(
Ntriazole-CH ), 54.9 (N
-CH ), 55.0 (CH), 120.0 (Cimidazole), 121.4
imidazole 2
2
(
(
(
(
CHtriazole), 124.5 (CHimidazole), 127.7 (CHaromatic), 128.6 (CHaromatic), 128.7
CHaromatic), 129.0 (CHaromatic), 129.3 (CHaromatic), 129.4 (CHaromatic), 134.1
Caromatic), 134.7 (Caromatic), 136.3 (Ctriazole), 144.3 ppm (C-Pt); HRMS
positive ESI): m/z calcd for C H I N Pt: 878.050 [M+H]; found:
3
2
(2 mL). The mixture was then heated overnight at 708C. The sol-
vent was then removed under vacuum. The residue was purified
by means of silica gel chromatography using a mixture of ethyl
26
33 2
6
8
78.039.
acetate and cyclohexane 1:2 and then 1:1 to afford compound 22
1
Compound 17: A solution of 9 (55 mg, 0.076 mmol) in THF (4 mL)
as a yellow-brown oil (29 mg, 41%). H NMR (CDCl , 300 MHz,
3
[37]
and a solution of Fmoc-Lys(N )-OMe (66 mg, 0.162 mmol) in THF
208C): d=0.87 (s, 3H; CH3 oestrogen), 0.98–2.50 (br, 24H; 2CH and
3
(
4 mL) were added to a solution of [RuClCp*(PPh ) ] (9.0 mg,
11 CH ), 2.79 (br, 3H; CH and 1CH), 3.48 (br, 2H), 3.77 (br, 2H),
3
2
2
2
0
7
.011 mmol) in THF (3 mL). The mixture was then heated for 2 h at
08C. The solvent was then removed under vacuum. The residue
3.81 (s, 3H; Nimidazole-CH ), 4.18 (br, 1H; OH), 5.02 (br, 1H; OH), 5.80
3
(s, 2H; Nimidazole-CH ), 6.73 (br, 1H; Ar-H), 6.63 (m, 1H; Ar-H), 6.73 (s,
2
was purified by means of silica gel chromatography using dichloro-
methane followed by a mixture of ethyl acetate and dichlorome-
1H; CHimidazole), 7.13 (d, J=9.0 Hz, 1H; 1Ar-H), 7.32–7.43 (br, 5H; Ar-
H), 7.56 (m, 2H; 2CHpyridine), 7.74 (br, 1H; CH
), 7.80 (s, 1H;
pyridine
13
thane 1:5 to afford compound 17 as a yellow-brown oil (51 mg,
CHtriazole), 9.05 ppm (d, J=5.4 Hz, 2H; 2CHpyridine); C NMR (CDCl3,
75 MHz, 208C): d=11.9 (CH3 oestrogen), 24.5, 26.3, 27.4, 28.7, 29.6,
1
5
9%). H NMR (CDCl , 300 MHz, 208C): d=1.67–1.78 (br, 6H; 3CH ),
3
2
3
.74 (s, 3H; OCH ), 3.80 (s, 3H; N
-CH ), 4.10–4.24 (br, 3H),
30.2, 33.3, 36.3 (Nimidazole-CH ), 38.0, 39.3, 43.8, 44.9, 47.0, 47.6, 48.8,
3
imidazole
3
3
1
036
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemPlusChem 2012, 77, 1028 – 1038