ACCEPTED MANUSCRIPT
(1H, dd, JHH = 4.8 Hz, 7.6 Hz, H4a), 4.39-4.34 (1H, dd, JHH = 8.4 Hz, 12.8 Hz, H5’),
4.56-4.51 (1H, dd, JHH = 8.4 Hz, 12.8 Hz, H5’), 5.61-5.58 (1H, dd, JHH = 3.2 Hz, 8.4 Hz,
H7), 5.87-5.84 (1H, dd, JHH = 3.6 Hz, 10.0 Hz, H3), 6.00-5.96 (1H, dd, JHH = 4.8 Hz,
10.0 Hz, H4), 6.69-6.68 (1H, dd, JHH = 3.2 Hz, H2), 7.17-7.13 (2H, dd, JHH = 8.8 Hz,
H11), 8.21-8.18 (2H, dd, JHH = 8.8 Hz, H10). 13C NMR (100 MHz, CDCl3): δppm: 25.47
(C6), 50.12 (C5), 57.18 (C4a), 61 (CH2-5’), 71.19 (C7), 115.91-115.69 (C11), 118.67 (C3),
121.52 (CF3), 124.27 (C4), 131.56 (C12), 132.17 (C10), 134.07 (C2), 164.76 (C9), 172.13
(C5’, keto ester), 195.01 (C8, keto). Anal. Calcd. C17H14F4N2O3: C, 55.14; H, 3.81; N,
7.57; Found: C, 55.19; H, 3.77; N, 7.41. MS (ESI) m/z: 371 (M+1), 372 (M+2), 393
(M+Na+), 394 [(M+1)+Na+], 763 (2M+Na+).
2,2,2-Trifluoroethyl
7-(4-chlorobenzoyl)-4a,5,6,7-tetrahydropyrrolo[1,2-
o
b]pyridazine-5-carboxylate (3b): Yellow crystals, mp: 118-120 C. IR (KBr): ν/cm-1:
1
3094, 2914, 1746, 1687, 1592, 1498, 1266. H NMR (400 MHz, CDCl3): δppm: 2.34-
2.31 (1H, dd, JHH = 4.8 Hz, 8.8 Hz, 13.2 Hz, H6a), 2.44-2.41 (1H, dd, JHH = 3.6 Hz, 8.8
Hz, 13.2 Hz, H6b), 3.31-3.26 (1H, ddd, JHH = 3.6 Hz, 4.4 Hz, 8.4 Hz, H5), 4.24-4.21 (1H,
dd, JHH = 4.8 Hz, 7.2 Hz, H4a), 4.39-4.34 (1H, dd, JHH = 8.4 Hz, 12.8 Hz, H5’), 4.56-4.50
(1H, dd, JHH = 8.4 Hz, 12.8 Hz, H5’), 5.58-5.55 (1H, dd, JHH = 3.2 Hz, 8.4 Hz, H7), 5.86-
5.83 (1H, dd, JHH = 2.4 Hz, 10.0 Hz, H3), 5.99-5.95 (1H, dd, JHH = 6.4 Hz, 10.0 Hz, H4),
6.68-6.67 (1H, d, JHH = 3.2 Hz, H2), 7.47-7.44 (2H, d, JHH = 8.8 Hz, H11), 8.11-8.09
(2H, dd, JHH = 8.4 Hz, H10). 13C NMR (100 MHz, CDCl3): δppm: 25.31 (C6), 49.84 (C5),
57.19 (C4a), 61 (CH2-5’), 71.24 (C-7), 118.68 (C3), 121.72 (CF3), 125.13 (C4), 128.39
(C11), 134.29 (C10), 131.42 (C12), 134.29 (C2), 146.07 (C9), 172.45 (C5’, keto ester),
195.12 (C8, keto). Anal. Calcd. C17H14ClF3N2O3: C, 52.79; H, 3.65; N, 7.24; Found: C,
52.77; H, 3.67; N, 7.18.
2,2,2-Trifluoroethyl
7-(4-methylbenzoyl)-4a,5,6,7-tetrahydropyrrolo[1,2-
o
b]pyridazine-5-carboxylate (3c): Yellow crystals, mp: 147-149 C. IR (KBr): ν/cm-1:
1
3092, 2914, 1741, 1679, 1607, 1503, 1436, 1271. H NMR (400 MHz, CDCl3): δppm
:
2.41 (3H, s, CH3-12), 2.36-2.34 (1H, dd, JHH = 4.8 Hz, 8.0 Hz, 13.2 Hz, H6a), 2.39-2.37
(1H, dd, JHH = 4.0 Hz, 8.8 Hz, 13.2 Hz, H6b), 3.31-3.26 (1H, ddd, JHH = 3.2 Hz, 4.8 Hz,
8.4 Hz, H5), 4.33-4.30 (1H, dd, JHH = 4.8 Hz, 8.0 Hz, H4a), 4.42-4.34 (1H, dd, JHH = 8.4
Hz, 12.8 Hz, H5’), 4.58-4.48 (1H, dd, JHH = 8.4 Hz, 12.8 Hz, H5’), 5.65-5.62 (1H, dd,
JHH = 4.0 Hz, 8.4 Hz, H7), 5.87-5.83 (1H, dd, JHH = 3.2 Hz, 10.0 Hz, H3), 5.99-5.95 (1H,
dd, JHH = 5.2 Hz, 10.0 Hz, H4), 6.92-6.68 (1H, dd, JHH = 3.2 Hz, H2), 7.29-7.26 (2H, d,
JHH = 8.0 Hz, H11), 8.05-8.03 (2H, dd, JHH = 8.0 Hz, H10). 13C NMR (100 MHz, CDCl3):
δppm: 21.66 (CH3-12), 27.56 (C6), 43.71 (C5), 57.31 (C4a), 61 (CH2-5’), 70.92 (C7),
117.08 (C3), 121.65 (CF3), 124.84 (C4), 129.47 (C11), 134.95 (C10), 133.52 (C12), 134.70
(C2), 145.38 (C9), 172.03 (C5’, keto ester), 195.26 (C8, keto). Anal. Calcd.
C18H17F3N2O3: C, 59.02; H, 4.68; N, 7.65; Found: C, 59.11; H, 4.61; N, 7.55. MS (ESI)
m/z: 389 (M+Na+), 390 [(M+1)+Na+], 755 (2M+Na+), 756 [(2M+1)+Na+].
Ethyl
7-(4-fluorobenzoyl)-5-(trifluoromethyl)-4a,5,6,7-tetrahydropyrrolo[1,2-b]
o
pyridazine -6-carboxylate (4a): White crystals, mp: 141-142 C. IR (KBr): ν/cm-1:
1
3090, 2981, 1730, 1684, 1590, 1502, 1470, 1262. H NMR (400 MHz, CDCl3): δppm
:
1.29-1.26 (3H, t, JHH = 7.2 Hz, CH3-6’), 3.63-3.57 (1H, dd, JHH = 8.8 Hz, H6), 3.67-3.63
(1H, dd, JHH = 8.8 Hz, H5), 4.22-4.17 (2H, q, JHH = 7.2 Hz, CH26’), 5.02-4.99 (1H, dd,
JHH = 5.2 Hz, 8.4 Hz, H4a), 5.77-5.75 (1H, d, JHH = 7.2 Hz, H7), 5.88-5.85 (1H, dd, JHH
9