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4.2.13. 4-Benzyl-2-phenoxycarbonyloxymethyl-1-(3,4,5-
trimethoxybenzoyl)piperazine (14). This compound
(1.8 g, 99%) was prepared following the same procedure
as described in Serradji et al.12 Rf: 0.71 (MeOH/CH2Cl2,
3:97, v/v); IR (m cmꢀ1) 1757 (C@O carbonate), 1650
(C@O amide), 1584 (ArC@C); 1H NMR d 7.49–7.00
(m, 10H, ArH), 6.59 (s, 2H, ArH), 5.26 (m, 2H,
CH2O), 4.80–3.80 (m, 4H, CH-Ph, piperazine), 3.79 (s,
3H,CH3O), 3.69 (s, 6H, CH3O), 3.60–2.15 (m, 5H,
CH–Ph, piperazine).
4.2.18. 3-N,N-Diethylaminocarbonyloxymethyl-1-(3,4,5-
trimethoxybenzoyl)-4-(methoxycarbonyldiphenylmeth-
yl)piperazine (19). Compound 19 was prepared follow-
ing the same process as for the compound 3, but from
methyl 2-bromo-2,2-diphenylacetate and 7. A recrystal-
lization from CH2Cl2/hexane yielded 400 mg (14%) of
the title compound; Rf: 0.1 (MeOH/CH2Cl2, 2:98, v/v);
mp 149.9 ꢁC; IR (m cmꢀ1) 1729 (C@O ester), 1694
(C@O carbamate), 1633 (C@O amide), 1584 (ArC@C);
1H NMR d 7.38 (m, 4H, ArH), 7.23 (m, 6H, ArH),
6.51 (s, 2H, ArH), 3.96 (m, 3H, CH2OC@O, piperazine),
3.76 and 3.74 (2s, 9H, CH3O), 3.72 (s, 3H, CH3OC@O),
3.65–2.30 (m, 10H, N(CH2CH3)2, piperazine), 0.97 (m,
6H, CH3); 13C NMR d 172.89 (C@O ester), 170.75
(C@O amide), 153.07, 140.20, 139.93, 131.05, 128.86,
128.59, 128.05, 127.95, 127.53, 127.39, 104.23 (ArC@C),
78.64 (CH2 ester), 61.47 (CH2O), 60.68, 56.12
(CH3O), 53.25 (CH3 ester), 52.27 (CH piperazine),
42.90, 41.43 (NCH2CH3), 13.50 (NCH2CH3). Anal.
(C35H43N3O8Æ0.75H2O) C, H, N.
4.2.14. 4-Benzyl-2-N,N-diethylaminocarbonyloxymethyl-
1-(3,4,5-trimethoxybenzoyl)piperazine,
hydrochloride
(15). This compound (1.41 g, 93%) was prepared as de-
scribed for the compound 6; Rf: 0.20 (MeOH/CH2Cl2,
5:95, v/v); mp 180.6 ꢁC; IR (m cmꢀ1) 3451 (NH+), 1720
(C@O carbamate), 1657 (C@O amide), 1584 (ArC@C);
1H NMR d 12.53 (br s, 1H, NH+), 7.61 (s, 2H, ArH),
7.36 (s, 3H, ArH), 6.62 (s, 2H, ArH), 5.06 (br s, 2H,
piperazine), 4.39 (br s, 2H, piperazine), 4.13 (br s,
2H, CH2O), 3.77 (s, 9H, CH3O), 3.53–2.69 (m, 9H,
CH2-Ph, N(CH2CH3)2, piperazine), 1.1 (m, 6H, CH3).
Anal. (C27H38N3ClO6Æ2H2O) C, H, N.
4.2.19. 2-N,N-Diethylaminocarbonyloxymethyl-4-(4-hy-
droxy-3,5-dimethoxybenzoyl)-1-(3,4,5-trimethoxybenzo-
yl)piperazine (20). A mixture of 16 (free base, 3 g,
7.33 mmol), syringic acid (1.5 g, 8.06 mmol), N,N0-dic-
yclohexylcarbodiimide (1.55 g, 8.06 mmol) and 1-
hydroxybenzotriazole (1.2 g, 8.06 mmol) in CH2Cl2was
refluxed overnight. The mixture was then filtered and
the filtrate washed with saturated NaHCO3 solution
and water, dried (MgSO4), filtered and the solvent elim-
inated. The residue was chromatographed through a sil-
ica gel column using MeOH/CH2Cl2 (1:99, v/v) as eluent
and recrystallized from MeOH/Et2O. The titled com-
pound was obtained (3.67 g, 84.5%) as white crystals;
Rf: 0.21 (MeOH/CH2Cl2, 5:95, v/v); mp 129.3 ꢁC; IR
(m cmꢀ1) 3373 (OH), 1686 (C@O carbamate), 1617
4.2.15. 2-N,N-Diethylaminocarbonyloxymethyl-1-(3,4,5-
trimethoxybenzoyl)piperazine, hydrochloride (16). This
compound (1.2 g, 85%) was prepared as described for
7; Rf: 0.22 (MeOH/CH2Cl2, 5:95, v/v); mp 194.9 ꢁC;
IR (m cmꢀ1) 3423 (NH2+), 1690 (C@O carbamate),
1
1640 (C@O amide), 1585 (ArC@C); H NMR d 9.75
(br s, 2H, NH2+), 6.58 (s, 2H, ArH), 5.35–3.90 (m,
5H, CH2O, piperazine), 3.80 (s, 9H, CH3O), 3.70–2.70
(m, 8H, N(CH2CH3)2, piperazine), 1.00 (t, J = 6.66 Hz,
6H, CH3); 13C NMR d 170.46 (C@O amide), 155.35
(C@O carbamate), 153.40, 139.75, 129.27, 104.40
(ArC@C), 61.43 (CH2O), 60.83, 56.27 (CH3O), 43.42,
42.78, 41.92, 41.32 (NCH2CH3 carbamate, piperazine),
13.99, 13.34 (NCH2CH3). Anal. (C20H32N3ClO6Æ0.5-
H2O) C, H, N.
1
(C@O amide), 1586 (ArC@C); H NMR d 6.61 (s, 2H,
ArH), 6.57 (s, 2H, ArH), 5.69 (s, 1H, OH), 5.30–3.90
(m, 5H, CH2OC@O, piperazine), 3.80 (s, 15H, CH3O),
3.60–2.40 (m, 8H, N(CH2CH3)2, piperazine), 1.01 (m,
6H, CH3); 13C NMR d 171.06, 170.62 (C@O amide),
155.05 (C@O carbamate), 153.26, 146.91, 139.46,
136.58, 130.21, 125.35, 104.42, 104.25 (ArC@C), 60.89
(CH2O), 60.76, 56.38, 56.15 (CH3O), 41.72, 41.01
(NCH2CH3), 13.80, 13.29 (NCH2CH3). Anal.
(C29H39N3O10Æ1.5H2O) C, H, N.
4.2.16. 3-N,N-Diethylaminocarbonyloxymethyl-1-(3,4,5-
trimethoxythiobenzoyl)piperazine (17). The same proce-
dure as for the preparation of the compound 41 was fol-
lowed to give 1.1 g (62.4%) of the compound 17; Rf: 0.18
(MeOH/CH2Cl2, 5:95, v/v).
4.2.17. 3-N,N-Diethylaminocarbonyloxymethyl-4-(3,4,5-
trimethoxybenzoyl)-1-(3,4,5-trimethoxythiobenzoyl)pi-
perazine (18). The same procedure as described for 2
but at room temperature was followed to lead to 18
(150 mg, 41%); Rf: 0.42 (MeOH/CH2Cl2, 5:95, v/v);
mp 100.9 ꢁC; IR (m cmꢀ1) 1691 (C@O carbamate),
4.2.20. 2-N,N-Diethylaminocarbonyloxymethyl-4-(phen-
yl(pyridin-4-yl)methyl)-1-(3,4,5-trimethoxybenzoyl)piper-
azine (21). The same procedure as for the preparation of
compound 3 was used to prepare the compound 21
(890 mg, 53%) as white crystals from 4-[chloro(phen-
yl)methyl]pyridine and 16: Rf: 0.44 (MeOH/CH2Cl2,
5:95, v/v); mp 79.1 ꢁC; IR (m cmꢀ1) 1692 (C@O carba-
mate), 1662 (C@O amide), 1583 and 1505 (ArC@C); 1H
NMR d 8.40 (s, 1H, ArH), 7.54 (s, 2H, ArH), 7.39 (m,
2H, ArH), 7.12 (m, 4H, ArH), 6.54 (s, 2H, ArH), 5.20-
3.85 (m, 4H, CH2O, Pyr–CH–Ph, piperazine), 3.78 and
3.75 (2s, 9H, CH3O), 3.75–2.50 (m, 8H, N(CH2CH3)2,
piperazine), 2.25–1.90 (m, 2H, piperazine), 1.06 (m, 3H,
CH3), 0.91 (m, 3H, CH3); 13C NMR d 170.27 (C@O
amide), 161.69, 161.52, 153.16, 149.10, 140.43, 140.28,
139.10, 136.85, 131.02, 128.73, 128.02, 127.87, 127.54,
1
1631 (C@O amide), 1584 (ArC@C); H NMR d 6.58
(s, 2H, ArH), 6.45 (m, 2H, ArH), 5.30–4.70 (m, 2H,
piperazine), 4.50–4.00 (m, 3H, CH2O, piperazine), 3.80
and 3.77 (2s, 18H, CH3O), 3.60–2.60 (m, 8H,
N(CH2CH3)2, piperazine), 1.03 (m, 6H, CH3); 13C
NMR d 202.23 (C@S), 170.54 (C@O amide), 155.00
(C@O carbamate), 153.24, 139.55, 138.43, 137.53,
129.83, 129.62, 104.31 (ArC@C), 61.15 (CH2O), 60.70,
60.65, 56.12 (CH3O), 51.65, 49.30, 48.77 (piperazine),
41.75, 41.00 (NCH2CH3), 13.93, 13.26 (NCH2CH3).
Anal. (C30H41N3O9S) C, H, N.