Design, synthesis and characterization of 1H-pyridin-4-yl-3, 5-disubstituted indazoles and their anti-inflammatory and analgesic activity.
VEERA REDDY.ARAVA.*
1
, SURENDRA REDDY. GOGIREDDY
1
,
DUBEY. P.K
2 , MADHAVA REDDY.B
3 , & VEERESH. B 3 .
1
R&D Centre, Suven Life Sciences Ltd, Plot No#18,Phase-III, Jeedimetla,
Hyderabad-500055, India.
E-mail: reddyvenis@rediffmail.com
2
Department of Chemistry, J.N.T. University, Hyderabad-500072, India.
3 Department of Pharmacology & Toxicology, G. Pulla Reddy College of Pharmacy,
Mehdipatnam, Hyderabad-500028, India
1.
General information …………………………………………………………….S2
2. Experimental …………………………………………………………………….S2-S9
2. Copies of NMR spectra for compounds 3a-b, 4a-g, 5a-g & 6a-b ………………S9-S26
-S1-

1.
General Information
All reagents were obtained commercially and were of the highest commercial quality and used without further purification. Solvents were freshly distilled and used. Melting points were determined in open capillaries and are uncorrected. TLC or HPLC are routinely used to check the purity of all compounds. IR spectra were recorded on a Perkin-Elmer model 2000 instrument in
KBr phase.
1
H-NMR (400 MHz) and
13
C-NMR (100 MHz) spectra were recorded in CDCl
3 or
DMSO using Bruker instrument and Mass spectra were recorded on a Perkin-Elmer mass spectrometer operating at 70 eV.
2 . Experimental
2.1 To a solution of 2-cyano-4-chloropyridine 2 (50 g, 0.361 mol), methyl 1 H -indazole-3carboxylate 1a (63.5 g, 0.361mol) in DMSO (300 mL), CuI (6.87 g, 0.036 mol), L -proline (8.3 g,
0.0722 mol) and cesium carbonate (235.2 g, 0.722 mol) were added at RT. Reaction mass was stirred for 6-12 h at 75-80°C. After completion of reaction, the reaction mass was quenched into water (2 Lt) and stirred for 30 min. The undissolved substances were filtered through celite pad.
To the filtrate pH was adjusted to 2.0-2.5 with Con.HCl to get the crude product (58 g). This crude product was recrystallized from ethyl acetate to get the desired pure product (55 g).
2.1b 5-Bromo-1-(2-cyano-pyridin-4-yl)-1H-indazole-3-carboxylic acid (3b): Yield (61.2%);
MR: 256-258°C; IR(KBr): 1715 (C=O), 2247 (-CN) (cm
-1
);
1
H-NMR (DMSO, 400 MHz): δ
7.65 (d, 1H, J = 8.83 Hz), 8.12 (d, 1H, J = 9.1 Hz), 8.13 (dd, 1H, J
1
= 5.08 Hz, J
2
= 1.4 Hz), 8.19
(s, 1H), 8.42 (s, 1H), 8.84 (d, 1H, J = 5.46 Hz), 13.8 (s, 1H);
13
C-NMR (DMSO
,
400 MHz): δ
–
114.5, 117.3, 117.5, 119.3, 120.7, 124.6, 126.3, 131.7, 134.5, 138.3, 139.3, 146.3, 153.1, 162.5,
-S2-

ms: m/z 341, 343 [M
+
+2]. Anal .Calcd. for C
14
H
7
BrN
4
O
2
: C, 49.0; H, 2.06; N,16.33, Found: C,
49.20; H, 2.10; N,16.03.
2.2 General procedure for the preparation of 1-(2-cyanopyridin-4-yl)-1H-indazole-3-
carboxylic acid amides 4(b-g): To a solution of 1-(2-cyanopyridin-4-yl)-1 H -indazole-3carboxylic acid 3a ( 10 g, 0.037 mol) in ethylene dichloride(100 mL), thionyl chloride (9 g,
0.075 mol) was added at 40-45°C and maintained for 1 h at 80-85°C. Upon completion of the reaction, the solvent was distilled off completely under atmospheric pressure to get the acid chloride. To the acid chloride fresh ethylene dichloride (50 mL) was added and cooled to 15°C and diethyl amine (8 g, 0.111 mol) was added at 15-30°C to pH 8.0 - 8.5 and stirred for 30 min.
To the reaction mass water (50 mL) was added and the organic layer was separated and washed with water (10 mL).The organic layer was dried over anhydrous Na
2
SO
4 and concentrated to get the product.
2.2b 4-[3-(Pyrrolidine-1-carbonyl)-indazol-1-yl]-pyridine-2-carbonitrile (4b): Yield(74%);
MR: 182-185°C; IR(KBr): 1613 (C=O), 2240 (-CN) (cm
-1
);
1
H-NMR (DMSO, 400 MHz) : δ
1.86-1.97 (m, 4H), 3.56 (t, 2H, J =6.68 Hz), 3.94 (t, 2H, J = 6.51 Hz), 7.42 (t, 1H, J = 7.53 Hz),
7.60 ( t, 1H, J = 7.71 Hz), 8.18 (m, 2H), 8.23 (s, 1H), 8.47 (d, 1H, J = 1.38 Hz), 8.82 (d, 1H, J =
9.38 Hz); 13 C-NMR (DMSO, 100 MHz) : δ 23.7, 26.4, 47.0, 48.7, 112.1, 117.5, 118.5, 120.2,
123.4, 124.4, 125.8, 129.3, 134.4, 143.3, 138.8, 146.9, 153.0, 160.1; ms: m/z 318.3(317) (M
+
).
Anal .Calcd. for C
18
H
15
N
5
O: C, 68.13; H, 4.76; N, 22.07, Found: C, 68.29; H, 4.86; N, 22.19.
2.2c 4-[3-(Piperidine-1-carbonyl)-indazol-1-yl]-pyridine-2-carbonitrile (4c): Yield: (70%);
MR: 141-143 °C; IR(KBr): 1617 (C=O), 2235 (-CN) (cm
-1
);
1
H-NMR (CDCl
3,
400 MHz): δ 1.75
(s, 6H) 3.84 (s, 4H), 7.39 (t, 1H, J = 7.54 Hz), 7.60 (t, 1H, J = 7.74 Hz), 7.88 (d, 1H, J =
-S3-

8.56 Hz), 7.99 (dd, 1H, J
1
= 1.52, J
2
= 4.56 Hz), 8.08 (d, 1H, J = 8.08 Hz), 8.19 (s, 1H), 8.79 (d,
1H, J = 5.44 Hz); 13 C-NMR (CDCl
3,
100 MHz): δ 24.4, 25.6, 26.7, 43.5, 48.1, 110.5, 116.8,
117.0, 119.5, 123.1, 124.1, 126.0, 129.2, 135.1, 138.7, 144.0, 147.3, 152.2, 161.0; ms: m/z 332.2
(331.3) (M
+
). Anal .Calcd. for C
19
H
17
N
5
O: C, 68.87; H, 5.17; N, 21.13, Found: C, 68.70; H,
5.11; N, 21.33.
2.2d 4-[3-(Morpholine-4-carbonyl)-indazol-1-yl]-pyridine-2-carbonitrile (4d): Yield: (75%);
MR: 196-198°C; IR(KBr): 1630 (C=O), 2240 (-CN) (cm -1 ); 1 H-NMR (CDCl
3,
400 MHz): δ 3.78-
4.07(m, 8H),7.44 (t, 1H, J = 7.23 Hz),7.62 (t, 1H, J = 7.34 Hz), 7.88 (d, 1H, J = 8.52 Hz),7.98
(d, 1H, J = 4.96 Hz), 8.17 (s, 1H), 8.19 (d, 1H, J = 8.12 Hz), 8.82 (d, 1H, J = 5.44 Hz);
13
C-NMR
(CDCl
3,
100 MHz): δ 42.8, 47.5, 66.8, 67.0, 110.4, 116.6, 117.3, 119.7, 123.5, 124.4, 126.2,
129.4, 135.3, 138.8, 143.0, 147.2, 152.3, 161.1, ms: m/z 334.2 (333) (M
+
). Anal .Calcd. for
C
18
H
15
N
5
O
2
: C, 64.86; H, 4.54; N, 21.01, Found:C, 64.72; H, 4.61; N, 21.18.
2.2e 4-[3-(4-Methyl-piperazine-1-carbonyl)-indazol-1-yl]-pyridine-2-carbonitrile (4e): Yield:
(79%); MR: 176-178°C; IR(KBr):1629 (C=O), 2243 (-CN) (cm
-1
);
1
H-NMR (CDCl
3,
400 MHz):
δ 2.34 (s, 3H), 2.49 (m, 4H), 4.05-4.11 (m, 4H), 7.40 (t, 1H,
J = 7.54 Hz), 7.59 (t, 1H, J = 7.72
Hz), 7.86 (d, 1H, J = 8.56 Hz), 7.97 (d, 1H, J = 4.24 Hz), 8.13 (d, 1H, J = 8.16 Hz), 8.17 (s, 1H),
8.79 (d, 1H, J = 5.44 Hz); 13 C-NMR (CDCl
3,
100 MHz): δ 42.3, 45.9, 46.9, 54.6, 55.3, 110.5,
116.7, 117.1, 119.6, 123.3, 124.3, 126.1, 129.3, 135.2, 138.8, 143.3, 147.2, 152.3, 161.0; ms: m/z
347 (346) (M
+
). Anal .Calcd. for C
19
H
18
N
6
O: C, 65.88; H, 5.24; N, 24.26, Found: C, 65.99; H,
5.30; N, 24.46.
2.2f 4-[3-(4-Ethyl-piperazine-1-carbonyl)-indazol-1-yl]-pyridine-2-carbonitrile (4f): Yield
(85%); MR: 148-150°C; IR(KBr): 1617(C=O), 2238(-CN) (cm -1 ); 1 H-NMR (DMSO, 400
-S4-

MHz): δ 0.99 (t, 3H, J = 6.97 Hz), 2.32-2.4 (m, 6H), 3.72 (s, 2H), 3.84 (s, 2H), 7.40 (t, 1H, J =
7.44 Hz), 7.62 (t, 1H, J = 7.67 Hz), 7.98 (d, 1H, J = 8.01 Hz), 8.19 (s, 1H), 8.21 (s, 1H) 8.47 (s,
1H), 8.82 (d, 1H, J = 5.41 Hz);
13
C-NMR (100 MHz, DMSO): δ 12.2, 42.2, 46.9, 51.7, 52.4,
53.2, 112.2, 117.4, 118.6, 120.3, 122.6, 124.4, 125.5, 129.5, 134.4, 138.8, 143.1, 146.8, 153.0,
160.6; ms: m/z 361 (360) (M
+
). Anal .Calcd. for C
20
H
20
N
6
O: C, 66.65; H, 5.59; N, 23.32, Found:
C, 66.76; H, 5.63; N, 23.60.
2.2g 5-Bromo-1-(2-cyano-pyridin-4-yl)-1H-indazole-3-carboxylicacid diethylamide (4g):
Yield: (73%); MR:131-133°C ; IR(KBr): 1623 (C=O), 2239 (-CN) (cm
-1
);
1
H-NMR (CDCl
3 ,
400
MHz): δ 1.26-1.37 (m, 6H), 3.61(q, 2H), 3.74 (q, 2H),7.64 (dd, 1H, J
1
= 8.98, J
2
=1.40 Hz),
7.74(d, 1H, J = 8.92 Hz), 7.93(dd, 1H, J
1
= 5.48 Hz, J
2
= 2.04 Hz), 8.13(d, 1H, J = 1.80 Hz),
8.42 (s, 1H), 8.82 (d, 1H, J = 5.56 Hz);
13
C-NMR (100 MHz, CDCl
3
): δ 12.7, 14.7, 41.1, 43.3,
111.6, 116.6, 117.0, 117.5, 119.5, 126.4, 128.0, 132.2, 135.3, 137.4, 143.0, 147.0, 152.4, 161.2; ms: m/z 398, 400 [M
+
+2] . Anal .Calcd. for C
18
H
16
BrN
5
O: C, 54.28; H, 4.05 ; N,17.59, Found: C,
54.40; H, 4.21 ; N, 17.82.
2.3 General procedure for the preparation of 1-(2-carbamoylpyridin-4-yl) -1H-indazole-3-
carboxamides 5(b-g): To a solution of Conc.H
2
SO
4
(36 mL,) and water (0.32 mL, 0.018 mol), sodium chloride (0.1 g, 0.0017 mol) was added at 10-15°C over a period of 30 min, and was heated to 35°C.1-(2-cyano-pyridin-4-yl)-1 H -indazole-3-carboxylic acid diethylamide 4a (6 g
0.018 mol) was added at 35-40°C (by maintaining the temperature with external cooling) over a period of 30 min. The reaction mixture was stirred for 1h at 40-45°C, and after completion of the reaction, the mass was quenched into ice-water (250 mL) and stirred for 30 min at 10-15°C. The precipitated product is filtered and washed with chilled DM-Water (2x100 mL) to yield desired
-S5-

product.
2.3b 4-[3-(Pyrrolidine-1-carbonyl)-indazol-1-yl]-pyridine-2-carboxylic acid amide (5b):
Yield: (70%); MR: 119-121°C; IR(KBr): 1691(C=O),1610 (C=O) and 3447 (-NH) (cm
-1
);
1
H
NMR (DMSO, 400 MHz): δ 1.87 (m, 4H), 3.60 (t, 2H,
J = 6.60 Hz), 3.98 (t, 2H, J = 6.36 Hz),
7.44 (t, 1H, J = 7.48 Hz), 7.66 (t, 1H, J = 7.68 Hz), 7.85 (s, 1H), 8.09 (m, 2H), 8.25 (s, 1H), 8.27
(s, 1H) 8.45 (s,1H), 8.78 (d, 1H, J = 5.38 Hz);
13
C-NMR (DMSO, 100 MHz): δ 23.7, 26.4, 46.9,
48.7, 111.7, 113.4, 117.7, 123.5, 124.2, 125.7, 129.3, 138.9, 142.9, 147.4, 150.7, 152.6, 160.5,
165.7; ms: m/z 336.3 (335.0) (M
+
). Anal .Calcd. for C
18
H
17
N
5
O: C, 64.47; H, 5.11; N,
20.88.Found. C, 64.67; H, 5.22; N, 21.00.
2.3c 4-[3-(Piperidine-1-carbonyl)-indazol-1-yl]-pyridine-2-carboxylic acid amide (5c): Yield:
(98%); MR: 231-232°C; IR(KBr): 1708 (C=O), 1623 (C=O) and 3351(-NH) (cm
-1
);
1
H-NMR
(DMSO, 400 MHz): δ 1.55 (m, 6H), 3.74 (s, 4H), 7.42 (t, 1H, J = 7.51 Hz), 7.68 (t, 1H, J = 7.74
Hz), 7.84 (s, 1H), 7.98 (d, 1H, J = 8.08 Hz), 8.12 (m, 2H) 8.27 (s, 1H), 8.45 (d, 1H, J = 1.81 Hz),
8.78 (d, 1H, J = 5.38 Hz);
13
C-NMR (DMSO, 100 MHz): δ 24.3, 25.7, 26.7, 43.0, 47.9, 112.0,
113.5, 117.5, 122.5, 124.3, 125.3, 129.6, 138.9, 143.5, 148.1, 149.9, 151.5, 160.9, 164.9; ms: m/z
350.2 (349) (M
+
). Anal .Calcd. for C
19
H
19
N
5
O
2
: C, 65.32; H, 5.48; N, 20.04, Found:C, 65.45; H,
5.58; N, 20.20.
2.3d 4-[3-(Morpholine-4-carbonyl)-indazol-1-yl]-pyridine-2-carboxylic acid amide (5d):
Yield: (72%); MR: 192-198°C; IR(KBr): 1661(C=O), 1631(C=O) and 3365 (-NH) (cm
-1
);
1
H
NMR (DMSO, 400 MHz): δ 3.62 (m, 2H), 3.63 (m, 4H), 3.89 (m, 2H), 7.43 (t, 1H, J = 7.52 Hz),
7.65 (t, 1H, J = 7.74 Hz), 7.84 (s, 1H), 8.03 (d, 1H, J = 8.16 Hz), 8.08 (m, 2H), 8.27 (s, 1H), 8.42
(d, 1H, J = 1.84 Hz), 8.77 (d, 1H, J = 5.4 Hz); 13 C-NMR (DMSO, 100 MHz): δ 42.6, 47.5, 66.4,
-S6-

66.8, 111.8, 113.5, 117.7, 122.6, 124.2, 125.3, 129.3, 138.9, 142.2, 147.3, 150.7, 152.5, 161.1,
165.7; ms: m/z 352.2 (351.0) (M + ). Anal .Calcd. for C
18
H
17
N
5
O
3
: C, 61.53; H, 4.88; N, 19.93,
Found: C, 61.73; H, 4.99; N, 20.23.
2.3e 4-[3-(4-Methyl-piperazine-1-carbonyl)-indazol-1-yl]-pyridine-2-carboxylic acid amide
(5e): Yield: (62%); MR: 186-188°C; IR(KBr): 1697(C=O), 1661(C=O) and 3376 (-NH) (cm
-1
);
1
H NMR (DMSO, 400 MHz): δ 2.21 (s, 3H), 2.35 (m, 4H), 3.75 (m, 4H), 7.41 (t, 1H, J = 7.44
Hz), 7.67 (t, 1H, J = 7.73 Hz), 7.85 (s, 1H), 8.02 (d, 1H, J = 8.08 Hz), 8.09 (m, 2H), 8.26 (s,1H),
8.44 (d, 1H, J = 1.77 Hz), 8.79 (d, 1H, J = 5.39 Hz);
13
C-NMR (DMSO, 100 MHz): δ 42.1, 45.8,
46.8, 54.6, 55.4, 111.8, 113.5, 117.6, 122.5, 124.1, 125.3, 129.4, 138.9, 142.5, 147.3, 150.7,
152.6, 161.0, 165.7; ms: m/z 365.4 (364) (M
+
). Anal .Calcd. for C
19
H
20
N
6
O
2
: C, 62.62; H, 5.53;
N, 23.06, Found: C, 62.85; H, 5.43; N, 23.28.
2.3f 4-[3-(4-Ethyl-piperazine-1-carbonyl)-indazol-1-yl]-pyridine-2-carboxylic acid amide
(5f): Yield: (68%); MR: 200-203°C; IR(KBr): 1705(C=O), 1643(C=O) and 3452 (-NH) (cm
-1
);
1
H NMR (DMSO, 400 MHz): δ 0.99 (t, 3H, J = 7.05 Hz), 2.31 (q, 2H), 2.39 (m, 4H), 3.74 (m,
4H), 7.40 (t, 1H, J = 7.41 Hz), 7.67 (t, 1H, J = 7.72 Hz), 7.85 (s, 1H), 8.00 (d, 1H, J = 8.08 Hz),
8.08 (m, 2H), 8.26 (s, 1H), 8.43 (d, 1H, J = 1.52 Hz), 8.78 (d, 1H, J = 5.45 Hz);
13
C-NMR
(DMSO, 100 MHz): δ 12.2, 42.2, 46.9, 51.7, 52.4, 53.2, 111.8, 113.4, 117.6, 122.6, 124.1, 125.3,
129.4, 138.9, 142.6, 147.3, 150.7, 152.6, 161.0, 165.7; ms: m/z 379.2 (378) (M
+
). Anal .Calcd. for C
20
H
22
N
6
O
2
: C, 63.48; H, 5.86; N, 22.21, Found: C, 63.70; H, 6.02; N, 22.40.
2.3g 5-Bromo-1-(2-carbamoyl-pyridin-4-yl)-1H-indazole-3-carboxylic acid diethylamide (5g):
Yield: (79%); MR: 200-202°C; IR(KBr): 1691(C=O), 3418 (-NH) (cm
-1
);
1
H-NMR (DMSO, 400
MHz): δ 1.14 (t, 3H, J = 6.72 Hz), 1.26 (t, 3H, J = 6.81 Hz), 3.50 (q, 2H), 3.70 (q, 2H),
-S7-

7.71 (d, 1H, J = 8.51 Hz), 7.84 ( s, 1H), 8.04 (m, 2H), 8.20 (s, 1H), 8.24 (s, 1H), 8.40 (s, 1H),
8.76 (d, 1H, J =5.38 Hz); 13 C-NMR (DMSO, 100 MHz): δ 13.0, 15.0, 40.7, 43.3, 113.4, 113.8,
116.4, 117.5, 125.1, 127.3, 131.8, 137.7, 141.8, 147.0, 150.7, 152.6, 161.2, 165.5; ms: m/z 416,
418 [M
+
+2] (416) (M
+
). Anal .Calcd. for C
18
H
18
BrN
5
O
2
: C, 51.94; H, 4.36; N, 16.82, Found: C,
52.15; H, 4.59; N, 16.94.
2.4 General procedure for the preparation of 1-(2-methylcarbamoyl-pyridin-4-yl)-1H-
indazole-3-carboxaamides 6(b):
To a solution of 4a (5 g, 0.015 mol) in methanol (100 mL) was added thionyl chloride (7.5 g,
0.063 mol) at 40-45°C over a period of 10-15 min. The reaction mixture was stirred for 1 h at 50-
55°C. The solvent is distilled off to get the crude product. Fresh methanol (50.0ml) was added to the residue and mono methylamine gas was bubbled at 10-40°C over a period of 20 min. The reaction mass was stirred for 30 min at 25-30°C, distilled off the solvent to the get crude. Water
(10.0ml) and dichloromethane (20 mL) were added and stirred for 10 min. The organic layer is separated and concentrated completely to get the 6a , which was slurred in hexane (10 mL) and filtered to get the desired pure product.
2.4b N -methyl-4-(3-(pyrrolidine-1-carbonyl)-1 H -indazol-1-yl)picolinamide (6b) :Yield (52%); m.p.211.5 °C; IR (KBr): 1671.65 (C=O), 1625.0 and 3336.96 (-NHCH
3
) (cm -1 ); 1 H (400 MHz,
CDCl
3
): 1.94-2.0 (m, 4H), 3.06 (d, 3H, J = 4.88 Hz), 3.74 (t, 2H, J = 6.58 Hz), 4.07 (t, 2H, J =
6.48 Hz), 7.35 (t, 1H, J = 7.48 Hz), 7.51 (t, 1H, J = 7.66 Hz), 7.87 (d, 1H, J = 3.56 Hz), 7.93 (d,
1H, J = 8.52 Hz), 8.08 (s,1H), 8.44 (d, 1H, J = 8.04 Hz), 8.62 (d, 1H, J = 5.68 Hz), 8.65 (s, 1H).
13
C-NMR (100 MHz, CDCl
3
); δ 23.8, 26.1, 26.5, 46.9, 48.8, 110.6, 113.1, 117.1,
-S8-

123.8, 124.0, 126.3, 128.6, 138.9, 143.0, 148.0, 149.4, 151.7, 161.0, 164.1; ms: m/z 350 (349)
(M + ). Anal .Calcd. for C
19
H
19
N
5
O
2
: C, 65.32; H, 5.48; N, 20.04, Found: C, 65.54; H, 5.70; N,
20.18.
Copies of NMR Spectra
N
N
O
OH
N CN
3a
N
N
O
OH
N CN
3a
-S9-

Br
N
N
O
OH
N CN
3b
Br
N
N
O
OH
N CN
3b
-S10-

N
N
O
N
N CN
4a
N
N
O
N
N CN
4a
-S11-

N
N
O
N
N CN
4b
N
N
O
N
N CN
4b
-S12-

N
N
O
N
N CN
4c
N
N
O
N
N CN
4c
-S13-

N
N
O
N
O
N CN
4d
N
N
O
N
O
N CN
4d
-S14-

N
N
O
N
N
CH
3
N
4e
CN
N
N
O
N
N
CH
3
N
4e
CN
-S15-

N
N
O
N
N CH
3
N CN
4f
N
N
O
N
N CH
3
N CN
4f
-S16-

Br
N
N
O
N
N CN
4g
Br
N
N
O
N
N CN
4g
-S17-

N
N
O
N
N C
O
5a
NH
2
N
N
O
N
N C
5a
O
NH
2
-S18-

N
N
O
N
N CONH
2
5b
N
N
O
N
N CONH
2
5b
-S19-

N
N
O
N
N CONH
2
5c
N
N
O
N
N CONH
2
5c
-S20-

N
N
O
N
O
N CONH
2
5d
N
N
O
N
O
N CONH
2
5d
-S21-

N
N
O
N
N
CH
3
N CONH
2
5e
N
N
O
N
N
CH
3
N CONH
2
5e
-S22-

N
N
O
N
N CH
3
N CONH
2
5f
N
N
O
N
N CH
3
N CONH
2
5f
-S23-

Br
N
N
O
N
N CONH
2
5g
Br
N
N
O
N
N CONH
2
5g
-S24-

N
N
O
N
N C
O
6a
NHCH
3
N
N
O
N
N C
O
6a
NHCH
3
-S25-

N CONHCH
N
N
O
N
N CONHCH
3
6b
-S26-