D.-K. Kim et al. / Bioorg. Med. Chem. 9 (2001) 3013–3021
3017
4-(2-Ethoxy-5-(4-(ethoxycarbonylmethyl)piperidinylsulfo-
nyl)benzamido)-1-methyl-3-n-propylpyrazole-5-carboxa-
mide (8b). Yield 93%; mp 177–178 ꢁC (EtOAc/
hexanes); IR (neat) 3357, 3180, 3075 (NH), 1733, 1670,
4-(2-Ethoxy-5-(4-(ethoxycarbonylmethyl)piperazinylsul-
fonyl)benzamido)-1-methyl-3-n-propylpyrazole-5-carbox-
amide (8e). Yield 68%; mp 178–178.5 ꢁC (CHCl3/
EtOAc/hexanes); IR (neat) 3359, 3182 (NH), 1747,
1674, 1640 (C¼O), 1169 (SO2) cmꢂ1; 1H NMR (DMSO-
d6) d 0.90 (t, J=7.5 Hz, 3H, CH2CH2CH3), 1.16 (t,
J=7.2 Hz, 3H, CO2CH2CH3), 1.42 (t, J=6.9 Hz, 3H,
OCH2CH3), 1.53–1.65 (m, 2H, CH2CH2CH3), 2.46 (t,
J=7.5 Hz, 2H, CH2CH2CH3), 2.60 (br s, 4H, 2 NCH2),
2.88 (br s, 4H, 2 NCH2), 3.24 (s, 2H, NCH2CO2), 3.92
(s, 3H, NCH3), 4.05 (q, J=7.2 Hz, 2H, CO2CH2CH3),
4.31(q, J=6.9 Hz, 2H, OCH2CH3), 7.31(br s, H1 ,
CONH2), 7.43 (d, J=8.7 Hz, 1H, H-30), 7.78–7.90 (m,
3H, H-40, H-60 and CONH2), 9.64 (br s, 1H, NH); MS
(FAB) m/z 565 (MH+). Anal. calcd for C25H36N6O7S:
C, 53.18; H, 6.43; N, 14.88. Found: C, 53.01; H, 6.32; N,
15.03.
1
1640 (C¼O), 1168 (SO2) cmꢂ1; H NMR (DMSO-d6) d
0.89 (t, J=7.5 Hz, 3H, CH2CH2CH3), 1.15 (t, J=7.2
Hz, 3H, CO2CH2CH3), 1.16–1.29 (m, 2H, 2CHax), 1.42
(t, J=6.9 Hz, 3H, OCH2CH3), 1.53–1.65 (m, 3H, CH
and CH2CH2CH3), 1.71 (br d, J=12.6 Hz, 2H, 2 CHeq),
2.18–2.26 (m, 2H, 2NCHax), 2.21(d, J=6.6 Hz, 2H,
CH2CO2), 2.46 (dd, J=7.8, 7.5 Hz, 2H, CH2CH2CH3),
3.61(br d, J=11.4 Hz, 2H, 2NCHeq), 3.92 (s, 3H,
NCH3), 4.02 (q, J=7.2 Hz, 2H, CO2CH2CH3), 4.30 (q,
J=6.9 Hz, 2H, OCH2CH3), 7.33 (br s, 1H, CONH2),
7.41(d, J=8.7 Hz, 1H, H-30), 7.83 (dd, J=8.7, 2.4
Hz, 1H, H-40), 7.87 (br s, 1H, CONH2), 7.88 (d,
J=2.4 Hz, 1H, H-60), 9.60 (br s, 1H, NH); MS (FAB)
m/z 564 (MH+). Anal. calcd for C26H37N5O7S: C,
55.40; H, 6.62; N, 12.42. Found: C, 55.22; H, 6.69; N,
12.58.
4-(2-Ethoxy-5-(4-(2-ethoxycarbonylethyl)piperazinylsul-
fonyl)benzamido)-1-methyl-3-n-propylpyrazole-5-carbox-
amide (8f). Yield 95%; mp 160.5–161 ꢁC (EtOAc/
hexanes); IR (neat) 3365, 3191 (NH), 1726, 1673, 1643
4-(2-Ethoxy-5-(4-(2-ethoxycarbonylethyl)piperidinylsulfo-
nyl)benzamido)-1-methyl-3-n-propylpyrazole-5-carboxa-
mide (8c). Yield 90%; mp 174–175 ꢁC (EtOAc/
hexanes); IR (neat) 3358, 3202, 3180 (NH), 1730, 1668,
1
(C¼O), 1169 (SO2) cmꢂ1; H NMR (CDCl3) d 0.96 (t,
J=7.2 Hz, 3H, CH2CH2CH3), 1.22 (t, J=7.2 Hz, 3H,
CO2CH2CH3), 1.60 (t, J=7.2 Hz, 3H, OCH2CH3),
1.60–1.72 (m, 2H, CH2CH2CH3), 2.42 (t, J=7.2 Hz,
2H, CH2CH2CH3), 2.52–2.57 (m, 6H, 3 NCH2), 2.69 (t,
J=7.2 Hz, 2H, CH2CO2), 3.05 (br s, 4H, 2 NCH2), 4.07
(s, 3H, NCH3), 4.10 (q, J=7.2 Hz, 2H, CO2CH2CH3),
4.40 (q, J=7.2 Hz, 2H, OCH2CH3), 5.62 (br s, 1H,
CONH2), 7.17 (d, J=9.0 Hz, 1H, H-30), 7.69 (br s, 1H,
CONH2), 7.91(dd, J=9.0, 2.4 Hz, 1H, H-40), 8.63 (d,
J=7.2 Hz, 1H, H-60), 9.28 (br s, 1H, NH); MS (FAB)
m/z 579 (MH+). Anal. calcd for C26H38N6O7S: C,
53.96; H, 6.62; N, 14.52. Found: C, 54.03; H, 6.52; N,
14.39.
1
1640 (C¼O), 1170 (SO2) cmꢂ1; H NMR (DMSO-d6) d
0.89 (t, J=7.5 Hz, 3H, CH2CH2CH3), 1.09–1.21 (m,
3H, CH and 2CHax), 1.15 (t, J=6.9 Hz, 3H,
CO2CH2CH3), 1.39–1.47 (m, 2H, CHCH2CH2), 1.42 (t,
J=6.9 Hz, 3H, OCH2CH3), 1.52–1.65 (m, 2H,
CH2CH2CH3), 1.70 (br d, J=9.3 Hz, 2H, 2 CHeq), 2.16
(br t, J=10.5 Hz, 2H, 2NCHax), 2.25 (t, J=7.5 Hz, 2H,
CH2CO2), 2.46 (dd, J=8.1, 7.2 Hz, 2H, CH2CH2CH3),
3.61(br d, J=11.1 Hz, 2H, 2NCHeq), 3.92 (s, 3H,
NCH3), 4.01(q, J=6.9 Hz, 2H, CO2CH2CH3), 4.30 (q,
J=6.9 Hz, 2H, OCH2CH3), 7.33 (br s, 1H, CONH2),
7.41(d, J=8.7 Hz, 1H, H-30), 7.84 (dd, J=8.7, 2.4 Hz,
1H, H-40), 7.87 (br s, 1H, CONH2), 7.88 (d, J=2.4
Hz, 1H, H-60), 9.60 (br s, 1H, NH); MS (FAB) m/z
578 (MH+). Anal. calcd for C27H39N5O7S: C, 56.14;
H, 6.80; N, 12.12. Found: C, 56.29; H, 6.91; N,
11.90.
4-(5-(4-(Hydroxycarbonyl)piperidinylsulfonyl)-2-n-pro-
poxybenzamido)-1-methyl-3-n-propylpyrazole-5-carboxa-
mide (8g). Yield 99%; mp 171–172 ꢁC (MeOH/CHCl3);
IR (neat) 3346, 3183, 3075 (NH, CO2H), 1673, 1641
1
(C¼O), 1167 (SO2) cmꢂ1; H NMR (DMSO-d6) d 0.89
(t, J=7.5 Hz, 3H, CH2CH2CH3), 0.99 (t, J=7.5 Hz,
3H, OCH2CH2CH3), 1.51–1.65 (m, 4H, 2CHax and
4-(2-Ethoxy-5-(4-(3-ethoxycarbonylpropyl)piperidinylsul-
fonyl)benzamido)-1-methyl-3-n-propylpyrazole-5-carbox-
amide (8d). Yield 76%; mp 168–168.5 ꢁC (MeOH/
Et2O); IR (neat) 3365, 3179, 3074 (NH), 1733, 1670,
CH2CH2CH3), 1.76–1.85 (m, 4H,
2
CHeq and
OCH2CH2CH3), 2.00–2.02 (m, 1H, CHCO2), 2.41–2.52
(m, 4H, 2NCHax and CH2CH2CH3), 3.38–3.43 (m, 2H,
1
1639 (C¼O), 1167 (SO2) cmꢂ1; H NMR (DMSO-d6) d
2NCHeq), 3.91(s, 3H, NCH ), 4.19 (t, J=6.6 Hz, 2H,
3
0.89 (t, J=7.2 Hz, 3H, CH2CH2CH3), 1.15 (t, J=7.2
Hz, 3H, CO2CH2CH3), 1.06–1.18 (m, 5H, CHCH2CH2
and 2CHax), 1.40–1.51 (m, 2H, CHCH2CH2), 1.42 (t,
J=6.9 Hz, 3H, OCH2CH3), 1.52–1.62 (m, 2H,
CH2CH2CH3), 1.70 (br d, J=9.9 Hz, 2H, 2 CHeq), 2.18
(br t, J=10.8 Hz, 2H, 2NCHax), 2.23 (t, J=7.2 Hz, 2H,
CH2CO2), 2.46 (dd, J=8.1, 7.2 Hz, 2H, CH2CH2CH3),
3.61(br d, J=11.4 Hz, 2H, 2NCHeq), 3.92 (s, 3H,
NCH3), 4.02 (q, J=7.2 Hz, 2H, CO2CH2CH3), 4.30 (q,
J=6.9 Hz, 2H, OCH2CH3), 7.33 (br s, 1H, CONH2),
7.41(d, J=8.7 Hz, 1H, H-30), 7.82 (br s, 1H, CONH2),
7.84 (dd, J=8.7, 2.4 Hz, 1H, H-40), 7.88 (d, J=2.4 Hz,
1H, H-60), 9.60 (br s, 1H, NH); MS (FAB) m/z 592
(MH+). Anal. calcd for C28H41N5O7S: C, 56.83; H,
6.98; N, 11.84. Found: C, 56.99; H, 7.07; N, 11.71.
OCH2CH2CH3), 7.40 (d, J=8.7 Hz, 1H, H-30), 7.44 (br
s, 1H, CONH2), 7.83 (dd, J=8.7, 2.4 Hz, 1H, H-40),
7.81–7.87 (m, 2H, CONH2 and H-60), 9.67 (br s, 1H,
NH); MS (FAB) m/z 536 (MH+). Anal. calcd for
C24H33N5O7S: C, 53.82; H, 6.21; N, 13.08. Found: C,
54.01; H, 6.16; N, 12.96.
4-(5-(4-(Ethoxycarbonylmethyl)piperidinylsulfonyl)-2-n-
propoxybenzamido)-1-methyl-3-n-propylpyrazole-5-car-
boxamide (8h). Yield 95%; mp 171–172 ꢁC (EtOAc/
hexanes); IR (neat) 3348, 3182, 3074 (NH), 1741, 1670,
1
1641 (C¼O), 1168 (SO2) cmꢂ1; H NMR (DMSO-d6) d
0.89 (t, J=7.5 Hz, 3H, CH2CH2CH3), 0.99 (t, J=7.5
Hz, 3H, OCH2CH2CH3), 1.15 (t, J=7.2 Hz, 3H,
CO2CH2CH3), 1.17–1.29 (m, 2H, 2CHax), 1.52–1.65 (m,