1132
Valenta, Urban, Taimr, Polivka:
(CH3N); 2.29 – 2.56 m, 7 H; 3.01 dd, 1 H (J = 10.7, J′ = 4.2, H-5); 3.14 t, 1 H (J = 6,6); 3.24 –
3.38 m, 6 H; 4.30 and 4.48, 2 H (AB system, J = 15.2, ArCH2); 5.73 t, 1 H (NH, J = 5.8); 7.15 –
7.36 m, 5 H (Ar−H). 13C NMR spectrum (CDCl3, 50.3 MHz): 31.4 d (C-4); 34.9 t (C-3); 43.4 t (C-2′
and C-6′); 43.9 t (C-5); 45.8 q (CH3N); 46.2 t (C-6); 49.9 t (NCH2Ar); 54.4 t (C-3′and 5′); 127.5 d
(C-3 and C-5 of benzyl); 127.3 d (C-4 of benzyl); 128.4 d (C-2 and C-6 of benzyl); 135.9 s (C-1 of
benzyl); 157.6 s (C-7); 173.6 s (C-2). For C18H26N4O2 (330.4) calculated: 65.42% C, 7.93% H, 16.96% N;
found: 65.63% C, 7.99% H, 16.79% N.
4-(4-Benzhydrylpiperazin-1-ylcarbonylaminomethyl)-1-benzyl-2-oxopyrrolidine (IVb)
A mixture of IIIb (4.4 g, 14 mmol), VI (2.9 g, 14 mmol), and triethylamine (2.1 g, 21 mmol) in
anhydrous dioxane (40 ml) was refluxed for 3.5 h. After cooling, the solid was collected and the
filtrate evaporated. The oily residue was chromatographed on a column of silica gel (60 g). Elution
with dichloromethane gave 4.5 g (67%) base IVb, m.p. 164 – 165 °C (benzene). IR spectrum (Nujol):
708, 740 (5 adjacent Ar−H); 1 250, 1 490, 1 599, 1 604, 3 025, 3 060, 3 080 (Ar−H); 1 519, 1 643
(NCONH), 1 679 (N−CO in the ring); 3 408 (NH). Mass spectrum, m/z: 482 (M+, C30H34N4O2,
0.01), 315 (0.1), 230 (29), 207 (37), 168 (62), 91 (99), 56 (100). 1H NMR spectrum (CDCl3, 100
MHz): 7.10 – 7.50 m, 15 H (Ar−H); 4.86 bt, 1 H (NH); 4.50 and 4.30, 2 H (AB system, J = 14,
PhCH2N); 4.22 s, 1 H (Ar2CH−N). 13C NMR spectrum (CDCl3, 25.14 MHz): 30.11 t (C-3); 31.60 d
(C-4); 43.85 t (C-2′ and C-6′); 44.14 t (C-5); 46.46 t (C-6); 50.12 t (CH2 of benzyl); 51.46 t (C-3′and
C-5′); 75.89 d (Ar2CH); 127.13 d (C-4 of benzhydryl); 127.58 d (C-4 of benzyl); 127.88 d, 128.55 d,
128.70 d (C-2, C-3, C-5 and C-6 of benzhydryl); 136,20 s (C-1 of benzyl); 142.22 s (C-1 of benz-
hydryl); 157.83 s (C-7); 173.82 s (C-2). For C30H34N4O2 (482.6) calculated: 74.65% C, 7.10% H,
11.61% N; found: 74.78% C, 7.31% H, 11,43% N.
1-Benzyl-4-[4-(4,4′-difluorobenzhydryl)piperazin-1-ylcarbonylaminomethyl]-2-oxopyrrolidine (IVc)
A similar procedure starting from VI (ref.4; 1.9 g, 9.5 mmol) and IIIc (3.4 g, 9.5 mmol) in dioxane
(35 ml) gave 5.4 g of crude oily product which was chromatographed on silica gel (50 g). Elution
with chloroform saturated with ammonia gave 2.0 g (40%) of pure base IVc, m.p. 180 – 183 °C.
Analytical sample m.p. 179 – 181 °C (benzene–hexane). IR spectrum (Nujol): 707, 749, 831 (5 and
2 adjacent Ar−H); 1 220 (Ar−F); 1 519, 1 575 (NCONH); 1 646 (NRCO in five membered cycle);
1
1 502, 1 600, 3 030, 3 065 (Ar); 3 395 (NH). H NMR spectrum (CDCl3, 200 MHz): 2.18 – 2.55 m,
7 H; 2.97 dd, 1 H (J = 10.2, J′ = 4.3; H-5); 3.11 t, 1 H (J = 6.2); 3.22 t, 1 H (J = 5.6); 3.32 m, 5 H;
4.19 s, 1 H (Ar2CH); 4.29 and 4.45, 2H (AB system, J = 14.8, PhCH2); 5.17 t, 1 H (J = 5.7, NH); 6.95 dd,
4 H, J(H,H) = 8.9, J(H,F) = 8.9, 2 × H-3 and H-5 from 4-FC6H4); 7.14 – 7.34 m, 5 H (ArH of
benzyl); 7.29 dd, 4 H (J(H,H) = 8.9, J(H,F) = 2.8, 2 × H-2 and H-6 from 4-FC6H4). 13C NMR spec-
trum (CDCl3, 50.3 MHz): 31.6 d (C-4); 35.1 t (C-3); 43.8 t (C-2′ and C-6′); 44.1 t (C-5); 46.4 t
(C-6); 50.1 t (C-6); 51.3 t (C-3′, C-5′); 74.2 d (Ar2CH); 115.4 d (2 × C-3 and C-5 from 4-FC6H4,
J(F,C) = 21.2); 127.5 d (C-4 from PhCH2); 127.9 d (C-3 and C-5 from PhCH2); 128.6 d (C-2 and
C-6 from PhCH2); 129.1 d (2 × C-2 and C-6 from 4-FC6H4, J(C,F) = 7.7); 136.2 s (C-1 of PhCH2);
137.7 s (2 × C-1 of 4-FC6H4, J(C,F) = 3.2); 157.7 s (C-7); 161.8 s (2 × C-4 of 4-FC6H4, J(C,F) =
245.9); 173.8 s (C-2). For C30H32F2N4O2 (518.6) calculated: 69.48% C, 6.22% H, 7.33 F, 10.80% N;
found: 69.43 % C, 6.25% H, 7.05% F, 10.58% N.
1-Benzyl-4-(4-(2,3′-dichlorobenzhydryl)piperazin-1-ylcarbonylaminomethyl)-2-oxopyrrolidine (IVd)
A similar procedure starting from IIId (6.5 g, 16.9 mmol) and VI (ref.4; 3.5 g, 16.9 mmol) in dioxane
(60 ml) gave 10.1 g of crude product. Similar processing like in the preparation of IVc yielded 3.5 g
Collect. Czech. Chem. Commun. (Vol. 59) (1994)