126
Z. Riedl et al. / Tetrahedron 62 (2006) 121–129
4.1.3. 4-(5-Chloro-2-pivaloylaminophenyl)-2-methyl-6-
nitropyridazin-3(2H)-one (13b). Recrystallization from
acetonitrile yielded 0.467 g of product (64%); mp 180–
181 8C; IR (KBr) nmax: 3568, 3436, 3274, 2964, 2932, 2872,
1682, 1644, 1586, 1500, 1480, 1402, 1362, 928, 788,
754 cmK1: dH (CDCl3 200 MHz): 8.53 (s, 1H, 0NH), 8.19 (s,
7.82 (s, 1H, H-6), 7.65 (br d, JZ8.1 Hz, 1H), 7.59 (br d, JZ
8.2 Hz, 1H), 7.36 (br s, 1H, N–H), 7.24 (br m, 2H), 7.05 (br
d, JZ7.6 Hz, 1H), 6.95 (br t, JZ7.1 Hz, 1H), 6.89 (br t, JZ
7.6 Hz, 1H), 6.75 (br d, JZ7.5 Hz, 1H), 3.94 (s, 3H, CH3),
1.29 (s, 9H, C(CH3)3), 1.21 (s, 9H, C(CH3)3); dC (CDCl3,
100 MHz): 177.4, 176.7, 160.6, 141.6, 138.2, 137.9, 137.7,
134.9, 131.6, 130.9, 129.8, 128.6, 128.2, 127.0, 126.3,
125.5, 125.3, 124.7, 41.0, 39.6, 39.3, 27.6, 27.5. MS (ESI):
377, 359, 304, 303, 293, 57; HRMS (ESI) Calcd for
C27H33N4O3 [MCH]C461.2553, found: 461.2534.
0
0
1H, H-5), 7.71 (d, 1H, J3 ,4 Z8.6 Hz, H-3 ), 7.48 (dd,
0
0
0
0
0
0
0
J3 ,4 Z8.6 Hz, J4 ,6 Z2.4 Hz, 1H, H-4 ), 7.31 (d, J4 ,6
Z
2.4 Hz, 1H, H-60), 4.04 (s, 3H, CH3), 1.20 (s, 9H, C(CH3)3);
dC (CDCl3 50 MHz): 177.3 (OCC(CH3)3), 160.1 (C-3),
146.0 (C-6), 141.1 (C-20), 135.6 (C-4), 131.3 (C-50), 131.2
and 130.3 (C-40, and K60), 128.8 (C-10), 128.2 and 126.2
(C-30, and -5), 42.3 (CH3), 39.5 (C(CH3)3), 27.4 (C(CH3)3).
HRMS (ESI) Calcd for C16H18ClN4O4 [MCH]C365.1017,
found 365.1024.
4.1.7. 5-Bromo-2-methyl-4-(2-pivaloylaminophenyl)pyr-
idazin-3(2H)-one (25). The crude reaction mixture was
suspended with diethyl ether (5 mL), the white precipitated
solid was removed by filtration. This etheral mother liquor
was subjected to column chromatography (silica, eluent:
chloroform-methanol 100:1 mixture) and the product was
recrystallized from an ether–hexane mixture.
4.1.4. 5-Chloro-2-methyl-4-(2-pivaloylaminophenyl)pyr-
idazin-3(2H)-one (18). The crude reaction mixture was
purified by flash column chromatography on silica using a
CH2Cl2–MeOH 100:0.5 mixture as the eluent.
Yield: 0.131 g, 18%; mp: 114–116 8C; IR (KBr) nmax: 3338,
3065, 3032, 2966, 1674, 1639, 1604, 1507, 1486, 1463,
1435, 930, 756 cmK1; dH (CDCl3, 400 MHz): 8.06 (br s, 1H,
NH), 8.02 (s, 1H, H-6), 7.79 (dd, JZ8.2, 1.1 Hz, 1H, H-30),
7.45 (ddd, JZ7.8, 7.5, 1.5 Hz, 1H, H-40), 7.30 (dd, JZ7.08,
1.5 Hz, 1H, H-60), 7.24 (ddd, JZ7.8, 7.6, 1.2 Hz, 1H, H-5 ),
3.82 (s, 3H, CH3), 1.18 (s, 9H, C(CH3)3); dC (CDCl3,
100 MHz):176.8 (0CO), 159.0 (C-3), 139.6 (C-4), 139.4
(C-6), 136.4 (C-2 ), 130.6, 130.4 (C-50,60), 129.2 (C-5),
127.1 (C-10), 125.9 (C-30), 124.9 (C-40) 40.8 (CH3), 39.4
(C(CH3)3), 27.4 (C(CH3)3). Anal. Calcd for C16H18BrN3O2
(364.24): C, 52.76; H, 4.98; N, 11.54. Found: C, 52.65; H,
5.12; N, 11.45.
Yield: 0.063 g, 9.8%; mp: 120–124 8C; IR (KBr) nmax
:
3487, 3335, 2967, 1670, 1637, 1605, 1515, 1486, 1447,
1370, 1295, 1255, 1210, 1170, 1016, 957, 779, 752, 743,
712, 635 cmK1; dH (CDCl3, 400 MHz): 8.16 (br s, 1H, NH),
7.91 (s, 1H, H-6), 7.80 (dd, 1H, JZ8.7, 1.1 Hz, 1H, H-30 or
H-60), 7.45 (ddd, 1H, JZ7.8, 7.5, 1.7 Hz, H-40 or H-50), 7.31
(dd, 1H, JZ7.8, 1.7 Hz, H-300 or H-60), 7.23 (ddd, 1H, JZ
8.7, 7.6, 1.2 Hz, H-40 or H-5 ), 3.87 (s, 3H, CH3), 1.18 (s,
9H, C-(CH3)3); dC (CDCl3, 100 MHz):176.9, 159.4, 138.0,
137.5, 136.9, 136.8, 130.8, 130.4, 126.1, 125.2, 124.9, 40.9,
39.4, 27.4. MS (ESI): 322, 320, 304, 284, 228, 200, 57;
HRMS (ESI) Calcd for C16H19ClN3O2 [MCH]C320.1166,
found 320.1158.
4.1.8. 4-Bromo-2-methyl-5-(2-pivaloylaminophenyl)pyr-
idazin-3(2H)-one (26). The crude reaction mixture was
suspended with diethyl ether (5 mL) and the white
precipitated product was filtered off and recrystallized
from acetonitrile.
4.1.5. 4-Chloro-2-methyl-5-(2-pivaloylaminophenyl)pyr-
idazin-3(2H)-one (19). The crude reaction mixture was
purified by flash column chromatography on silica using a
CH2Cl2–MeOH 100:0.5 mixture as the eluent.
Yield: 0.277 g, 38%; mp: 181–186 8C; IR (KBr): nmax
:
Yield: 0.110 g, 17%; mp: O150 8C (decomposition); IR
(KBr) nmax: 3340, 1682, 1646, 1579, 1520, 1479, 1442,
1284, 1156, 1025, 873, 768, 755, 728, 674 cmK1; dH
(CDCl3, 400 MHz): 7.80 (dd, 1H, JZ8.7, 1.2 Hz, H-30 or
H-60), 7.69 (s, 1H, H-6), 7.52 (br s, 1H, NH), 7.50 (dd, 1H,
JZ7.7, 7.6 0Hz, H-40 or H-50), 7.32 (ddd, 1H, JZ8.7, 7.6,
1.2 Hz, H-4 or H-50), 7.24 (dd, 1H, JZ7.7, 1.3 Hz, H-30 or
H-60), 3.83 (s, 3H, CH3), 1.18 (s, 9H, C(CH3)3); dC (CDCl3,
100 MHz): 176.9, 157.3, 140.1, 137.1, 134.8, 133.7, 130.6,
128.9, 127.4, 125.9, 125.6, 41.0, 39.4, 27.4. MS (ESI): 322,
320, 304, 302, 246, 238, 236, 200, 85, 58, 57; HRMS (ESI)
Calcd for C16H19ClN3O2 [MCH]C320.1166, found:
320.1156.
3340, 3048, 2975, 1682, 1643, 1579, 1519, 1441, 1282,
1155, 769, 755, 644, cmK1; dH (CDCl3, 200 MHz): 7.78
(dd, JZ8.1, 1.2 Hz, 1H, H-30 or H-60), 70.61 (s, 1H, H-6),
7.50 (dd, JZ8.1, 7.3 Hz, 1H, H-40 or H-5 ), 7.34 (ddd, JZ
8.1, 7.5, 1.2 Hz, 1H, H-40 or H-50), 7.205 (br s, 1H, NH), 7.22
(dd, JZ7.5, 1.8 Hz, 1H, H-30 or H-6 ), 3.89 (s, 3H, CH3),
1.17 (s, 9H, C(CH3)3); dC (CDCl3, 50 MHz): 176.7, 157.4,
143.4, 136.8, 134.8, 134.2, 130.5, 128.4, 127.6, 125.9,
125.1, 41.3, 39.4, 27.3. Anal. Calcd for C16H18BrN3O2
(364.24): C, 52.76; H, 4.98; N, 11.54. Found: C, 52.88; H,
5.08; N, 11.65.
4.1.9. 2-Methyl-6-nitro-4,5-diphenylpyridazin-3(2H)-
one (11). 4,5-Dichloro-2-methyl-6-nitropyridazin-3(2H)-
one (10, 17.50 mmol, 3.92 g) and tetrakis(triphenylphos-
phine)-palladium(0) (0.88 mmol, 1.01 g) as catalyst were
dissolved in anhydrous toluene (90 mL) and the mixture was
stirred at room temperature under argon for 30 min.
Phenylboronic acid (36.0 mmol, 4.39 g) and a solution of
sodium carbonate (2 M, 35 mL) were then added and the
mixture was refluxed for 10 h. The cold mixture was poured
onto ice-water (200 mL), extracted with chloroform (3!
120 mL), and dried over anhydrous sodium sulphate.
4.1.6. 2-Methyl-4,5-bis(2-pivaloylaminophenyl)pyrida-
zin-3(2H)-one (20). The crude reaction mixture was
purified by flash column chromatography on silica using a
CH2Cl2–MeOH 100:0.5 mixture as the eluent.
Yield: 0.095 g, 10%; mp: O215 8C (decomposition); IR
(KBr) nmax: 3325, 2962, 2926, 1675, 1616, 1601, 1576,
1505, 1479, 1444, 1368, 1298, 1262, 1161, 1019, 771,
747 cmK1; dH (CDCl3, 400 MHz): 8.44 (br s, 1H, N–H),