M. Wenckens et al. / Bioorg. Med. Chem. 11 (2003) 1883–1899
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J=3 and 5 Hz, Th); 7.01 (d, 1H, J=1.1 Hz, Py); 6.85 (d,
1H, J=1.1 Hz, Py); 6.8 (d, 1H, J=3 Hz, Th); 6.76 (d,
1H, J=5 Hz, Th); 4.29 (t, 2H, J=6.5 Hz, CH2a);
2.41–2.30 (m, 4H, CH2g+CH2); 2.24 (s, 6H, N(CH3)2),
1.83 (m, 2H, CH2b); 1.03 (t, 3H, J=7.4 Hz, CH3). 13C
NMR (CDCl3) d 143.94; 143.08; 132.99; 131.91; 129.85;
129.09; 128.76; 128.40; 126.69; 124.72; 123.71; 121.43;
121.27; 77.29; 55.72; 45.35; 27.36; 25.79; 14.00. Anal. C,
H, N.
(CDCl3) d 7.50–7.20 (m, 5H, Ph); 7.03 (d, 2H,
J=8.2 Hz, PhOMe); 6.9 (d, 1H, J=2.3 Hz, Py); 6.77 (d,
2H, J=8.2 Hz, PhOMe); 5.56 (d, 1H, J=2.3 Hz, Py);
3.78, (s, 3H, OCH3); 3.57 (t, 2H, J=5 Hz, CH2a); 3.10
(t, 2H, J=6 Hz, CH2g); 2.81 (s, 6H, N(CH3)2); 2.53 (q,
2H, J=7.4 Hz, CH2); 1.92 (m, 2H, CH2b); 0.99 (t, 3H,
J=7.4 Hz, CH3). 13C NMR (CDCl3) d 158.70; 147.76;
140.71; 136.69; 133.64; 129.54; 129.18; 128.25; 127.14;
125.48; 113.37; 105.21; 75.62; 55.93; 54.98; 45.27; 27.86;
1
25.83; 22.55; 13.40. 42d: H NMR (CDCl3) d 7.50–7.20
(Z)-1,2-Di-(1-[3-N,N-Dimethylaminopropyloxy]-pyrazol-
4-yl)-1-phenyl-1-butene (15d). Using procedure B, Mix-
ture A and 2d (0.208 g, 0.70 mmol), after workup and
FC (heptane/ethylacetate/Et3N 1:1:0.1) gave 15d (0.25 g,
(m, 5H, Ph); 6.81 (d, 2H, J=8.2 Hz, PhOMe); 6.65 (d,
2H, J=8.4 Hz, PhOMe); 6.10 (d, 1H, J=2.2 Hz, Py);
4.0 (t, 2H, J=6.2 Hz, CH2a); 3.73 (s, 3H, OCH3); 3.20
(t, 2H, J=6 Hz, CH2g); 2.83 (s, 6H, N(CH3)2); 2.35 (q,
J=7 Hz, CH2); 2.10 (m, 2H, CH2b); 1.20 (t, 3H,
J=7 Hz, CH3). 13C NMR (CDCl3) d 158.38; 143.46;
142.53; 135.31; 132.44; 132.06; 129.32; 128.62; 128.46;
127.32; 127.18; 113.01; 104. 54.92; 45.34; 51; 76.14;
56.12; 28.12; 22.60; 13.98.
1
76%, Rf 0.1) as a colourless oil. H NMR (CD3OD) d
7.35–7.20 (m, 5H, Ph); 7.18 (d, 1H, J=1.1 Hz, Py); 7.14
(d, 1H, J=1.1 Hz, Py); 6.74 (d, 1H, J=1.1 Hz, Py); 6.69
(d, 1H, J=1.1 Hz, Py); 4.35 (t, 2H, J=6.5 Hz, CH2a);
4.25 (t, 2H, J=6.5 Hz, CH2a); 2.43 (t, 2H, J=7 Hz,
CH2g); 2.35 (t, 2H, J=7 Hz, CH2g); 2.18 (t, 2H,
J=7.4 Hz, CH2); 2.25 (s, 6H, N(CH3)2); 2.20 (s, 6H,
N(CH3)2); 1.87 (q, 2H, J=7.4 Hz, CH2b); 1.81 (q, 2H,
J=7.4 Hz, CH2b); 0.93 (t, 3H, J=7.4 Hz, CH3). 13C
NMR (CDCl3) d 142.34; 133.16; 123.85; 130.98; 129.71;
129.07; 128.31; 126.90; 121.52; 121.45; 120.98; 119.71;
77.54; 77.32; 55.75; 55.70; 45.33; 45.29; 28.61; 25.85;
25.76; 13.43. Anal. C, H, N.
(Z)-1-(1-[3-N,N-Dimethylaminopropyloxy]-pyrazol-5-yl)-
2-(4-benzyloxyphenyl)-1-phenyl-1-butene (32d) and (Z)-
2-(1-[3-N,N-dimethylaminopropyloxy]-pyrazol-5-yl)-1-(4-
benzyloxyphenyl)-1-phenyl-1-butene (43d). Using proce-
dure B, Mixture B and 4-benzyloxybromobenzene
(0.28 g, 1.1 mmol) after workup and purification as the
oxalates as described above gave 32d and 43d (0.26 g,
1
77%) (4:1) as white crystals. 32d: H NMR (CDCl3) d
(Z)-1-(1-[3-N,N-Dimethylaminopropyloxy]-pyrazol-5-yl)-
2-(2-methoxyphenyl)-1-phenyl-1-butene (30d) and (Z)-2-
(1-[3-N,N-dimethylaminopropyloxy]-pyrazol-5-yl)-1-(2-
methoxyphenyl)-1-phenyl-1-butene (41d). Using proce-
dure B, Mixture B and 2-iodoanisole (0.23 g, 1.1 mmol),
after FC (heptane/EtOAc/Et3N 1:1:0.1) afforded (0.22 g,
77%, Rf 0.3) of 30d and 41d (4:1) as an oil which was
purified as the oxalates to give 30d and 41d (4:1) in
7.50–7.2 (m, 10H, 2Ph); 7.06 and 6.83 (each a d, 2H,
J=8.6 Hz, C6H4); 6.96 (d, 1H, J=2.3 Hz, Py); 5.57 (d,
1H, J=2.3 Hz, Py); 4.99 (s, 2H, CH2Ph); 3.63 (t, 2H,
J=6.5 Hz, CH2a); 2.52 (q, 2H, J=7.4 Hz, CH2g); 2.17
(s, 6H, N(CH3)2); 2.25–2.15 (m, 2H, CH2); 1.65–1.5 (m,
2H, CH2b); 0.98 (t, 3H, J=7.1 Hz, CH3). 13C NMR
(CDCl3) d 158.91; 152.63; 142.97; 131.60; 131.56;
128.05; 126.37; 123.75; 123.26; 122.66; 122.55; 121.69;
108.56; 100.00; 68.54; 63.86; 48.85; 36.37; 21.82; 17.06
1
quantitative yield. 30d: H NMR (CDCl3) d 7.40–7.00
1
(m, 10H, Ph+C6H4+Py); 5.60 (d, 1H, J=2.3 Hz, Py);
4.35–4.20 (m, 2H, CH2a); 3.73 (s, 3H, OCH3); 2.6–2.3
(m, 2H, CH2g); 2.25–2.1 (m, 2H, CH2); 2.18 (s, 6H,
N(CH3)2); 1.58 (m, 2H, CH2b); 0.97 (t, 3H, J=7.5 H,
CH3). 13C NMR (CD3OD) d 165.25; 156.84; 145.98;
139.70; 136.75; 130.02; 129.09; 128.46; 128.19; 127.69;
127.28; 126.36; 119.91; 110.50; 105.08; 74.37; 60.07;
(one signal hidden). 43d: H NMR (CDCl3) d 7.50–7.2
(m, 10H, 2Ph); 7.6 (d, 1H, J=2.1 Hz, Py); 6.85 and 6.71
(each a d, 2H, J=9.0 Hz, Phe); 5.99 (d, 1H, J=2.3 Hz,
Py); 4.94 (s, 2H, CH2Ph); 4.05 (t, 2H, J=6.3 Hz, CH2a);
2.38 (q, 2H, J=7.7 Hz, CH2); 2.21 (s, 6H, N(CH3)2);
2.25–2.15 (m, 2H, CH2); 1.9–1.7 (m, 2H, CH2b); 0.97 (t,
3H, J=7.7 Hz, CH3). 13C NMR (CDCl3) d 158.89;
152.26; 134.78; 134.75; 128.26; 126.85; 124.93; 123.34;
122.86; 122.55; 121.96; 121.65; 119.38; 108.18; 99.98;
64.15; 63.74; 48.98; 36.33; 21.87; 16.80. Anal. C, H, N.
1
56.86; 42.01; 26.79; 22.70; 16.94; 13.01. 41d: H NMR
(CDCl3) d 7.40–7.00 (m, 10H, Ph+C6H4+Py); 5.77 (d,
1H, J=2.3 Hz, Py); 4.35–4.20 (m, 2H, CH2a); 3.57 (s,
3H, OCH3); 2.6–2.3 (m, 2H, CH2g); 2.25–2.1 (m, 2H,
CH2); 2.25 (s, 6H, N(CH3)2); 1.92 (m, 2H, CH2b); 1.12
(t, 3H, J=7.7 Hz, CH3). 13C NMR (CD3OD) d 165.24;
156.89; 142.10; 141.63; 135.44; 131.59; 130.30; 129.75;
129.07; 128.51; 126.76; 119.87; 111.30; 105.18; 75.57;
56.83; 54.42; 42.09; 25.79; 22.96; 12.63. Anal. C, H, N.
(Z)-1-(1-[3-N,N-Dimethylaminopropyloxy]-pyrazol-5-yl)-
2-(4-hydroxyphenyl)-1-phenyl-1-butene (33d) and (Z)-2-
(1-[3-N,N-dimethylaminopropyloxy]-pyrazol-5-yl)-1-(4-
hydroxyphenyl)-1-phenyl-1-butene (44d). Using the pro-
cedure for hydrogenolysis of 8d and 19d, a 4:1 mixture
of 32d and 43d (42 mg, 0.09 mmol) gave 33d and 44d
1
(Z)-1-(1-[3-N,N-Dimethylaminopropyloxy]-pyrazol-5-yl)-
2-(4-methoxyphenyl)-1-phenyl-1-butene (31d) and (Z)-2-
(1-[3-N,N-dimethylaminopropyloxy]-pyrazol-5-yl)-1-(4-
methoxyphenyl)-1-phenyl-1-butene (42d). Using proce-
dure B, Mixture B and 4-iodoanisole (0.25 g, 1.07 mmol)
after workup and FC (heptane/EtOAc/Et3N 1:1:0.1)
afforded (0.22 g, 77%, Rf 0.25) of 31d and 42d (4:1) as
an oil which was converted to oxalates as described
(4:1) (21 mg, 62%) as an oil. 33d: H NMR (CDCl3) d
7.50–6.9 (m, 5H, Ph); 7.01 (d, 1H, J=2.4 Hz, Py); 6.29
and 6.65 (each a d, 2H, J=8.1 Hz, C6H4); 3.71 (t, 2H,
J=5.8 Hz, CH2a); 3.25–3.05 (m, 2H, CH2g); 2.85 (s,
6H, N(CH3)2); 2.53 (q, 2H, J=7.5 Hz, CH2); 1.95–1.80
(m, 2H, CH2b); 0.98 (t, 3H, J=7.3 Hz, CH3). 44d: d
7.50–6.9 (m, 5H, Ph); 6.74 and 6.65 (each a d, 2H,
J=8.7 Hz, C6H4); 4.04 (t, 2H, J=5.8 Hz, CH2a);
3.25–3.05 (m, 2H, CH2g); 2.87 (s, 6H, N(CH3)2); 2.40
1
above to give (0.24 g) as white crystals. 31d: H NMR