5822
S. Fusi et al. / Tetrahedron Letters 49 (2008) 5820–5822
Table 2
s, CH3), 6.92 (1H, br s, NH), 7.49–7.79 (5H, m, Ph); dC (100 MHz,
Preparation of compounds 5 and 12–15
CDCl3) 12.9, 21.8, 68.6, 113.2, 113.6, 114.0, 117.5, 127.9, 129.2,
129.3, 131.4, 152.5, 153.9, 170.4; m/z (EI) 331 (M+, 100%); Anal.
Calcd for C17H12F3N3O: C, 61.63; H, 3.65; N, 12.68. Found: C,
61.51; H, 3.91; N, 12.71.
Ar
NC
Ar
CN
NC
CN
TFA (1.5 equiv)
TEA( 2 equiv)
N-(2,4-Dicyano-1,5-dimethyl-3-(40-methoxyphenyl)cyclopenta-
2,4-dienyl)-20,20,20-trifluoroacetamide (12): yellow solid, 72 mg
(26% yield), mp 185–187 °C; dH (400 MHz, CDCl3) 1.60 (3H, s,
CH3), 2.15 (3H, s, CH3), 3.85 (3H, s, OCH3), 6.90 (1H, br s, NH),
7.00 (2H, d, J = 7, Ar), 7.75 (2H, d, J = 7, Ar); dC (100 MHz, CDCl3)
12.9, 21.9, 55.5, 68.5, 111.0, 112.8, 113.5, 114.7, 117.8, 121.8,
129.8, 152.7, 155.2, 162.2, 170.5; m/z (ESI) 360 (MꢀH+ 100%); Anal.
Calcd for C18H14F3N3O2: C, 59.83; H, 3.91; N, 11.63. Found: C, 59.81;
H, 3.92; N, 11.66.
N
H
NHCOCF
3
8-11
12-15
Entry
Substrate
Product
Ar
C6H5
4-CH3O–C6H4
4-NO2–C6H4
2,4-NO2–C6H3
2-Thienyl
Yielda (%)
1
2
3
4
5
4
8
9
10
11
5
12
13
14
15
45
26
63
75
23
N-(2,4-Dicyano-1,5-dimethyl-3-(40-nitrophenyl)cyclopenta-
2,4-dienyl)-20,20,20-trifluoroacetamide (13): 218 mg, yellow so-
lid (63% yield), mp 199–200 °C; dH (400 MHz, CDCl3) 1.65 (3H, s,
CH3), 2.19 (3H, s, CH3), 6.91 (1H, br s, NH), 7.89 (2H, d, J = 7, Ar),
8.37 (2H, d, J = 7, Ar); dC (100 MHz, CDCl3) 13.1, 21.6, 68.9,
112.0, 112.7, 113.1, 116.53, 124.4, 129.1, 130.0, 135.0, 149.8,
150.9, 171.7; m/z (ESI) 375 (MꢀH+, 100%); Anal. Calcd for
a
Calculated by relative integration of the methyl groups in the 1H NMR spectra
(400 MHz, CDCl3).
N011
C
17H11F3N4O3: C, 54.26; H, 2.95; N, 14.89. Found: C, 54.32; H,
2.94; N, 14.93.
N-(2,4-Dicyano-1,5-dimethyl-3-(20,40-dinitrophenyl)cyclopenta-
2,4-dienyl)-20,20,20-trifluoroacetamide (14): 286 mg, pale yellow so-
lid (75% yield), mp 190–192 °C; dH (400 MHz, CDCl3) 1.63 (3H, s,
CH3), 2.15 (3H, s, CH3), 7.49 (1H, br s, NH), 7.82 (1H, d, J = 7, Ar),
8.63 (1H, d, J = 7, Ar), 9.13 (1H, s, Ar); dC (100 MHz, CDCl3) 14.1,
20.3, 69.2, 111.7, 112.3, 113.4, 116.2, 117.8, 121.2, 129.1, 131.2,
133.5, 146.7, 149.4, 150.2, 168.9; m/z (ESI) 420 (MꢀH+, 100%); Anal.
Calcd for C17H10F3N5O5: C, 48.47; H, 2.39; N, 16.62. Found: C, 48.56;
H, 2.38; N, 16.68.
F1b
N002
F3
F2
S1
F2b
F3b
F1
O003
N-(2,4-Dicyano-1,5-dimethyl-3-(thiophen-20-yl)cyclopenta-
2,4-dienyl)-20,20,20-trifluoroacetamide (15): yellow solid, 67 mg
(23% yield), mp 250 °C dec.; dH (400 MHz, CDCl3) 1.54 (3H, s,
CH3), 2.13 (3H, s, CH3), 6.64 (1H, br s, NH), 7.18 (1H, app t,
J = 6, H4(thiophene)), 7.61 (1H, d, J = 6, H3(thiophene)), 8.06 (1H, d,
J = 6, H5(thiophene)); dC (100 MHz, CDCl3) 12.9, 21.6, 68.8, 109.8,
111.1, 112.0, 114.6, 128.3, 130.7, 130.9, 132.0, 144.3, 171.8;
m/z (ESI) 336 (MꢀH+, 100%); Anal. Calcd for C15H10F3N3OS: C,
53.41; H, 2.99; N, 12.46. Found: C, 53.23; H, 3.05; N, 12.43.
N013
Figure 2. ORTEP drawing of compound 15 with 20% probability thermal ellipsoids.
compounds 5 and 12–15 in synthesis. Studies aimed at obtaining
enantiopure samples of 5 by reacting 4 in the presence of chiral
amines are in progress.
Preparation of compound 3: To a solution of 1,4-dihydropyridine
4 (1 mmol) in anhydrous CH2Cl2 (10 mL) kept at 0 °C by means of
an ice bath were sequentially added anhydrous TEA (2 equiv) and
TFA (1.5 equiv). The reaction mixture was then allowed to reach
room temperature, and was stirred for 5 min. After this time, the
solvent was evaporated, and the oil so obtained was purified by
flash chromatography (petroleum ether–ethyl acetate 3:1) to give
compound 3 as a colourless solid, 305 mg (92% yield), mp 55–
57 °C; dH (400 MHz, CDCl3) 2.41 (6H, s, CH3), 4.34 (1H, s, H-4),
7.18–7.40 (5H, m, Ph); dC (100 MHz, CDCl3) 20.2, 43.5, 102.2,
113.3, 115.8, 126.8, 128.9, 129.6, 136.4, 148.3, 161.8; m/z (EI)
331 (M+, 100%); Anal. Calcd for C17H12F3N3O: C, 61.63; H, 3.65;
N, 12.68. Found: C, 61.55; H, 3.85; N, 12.65.
General procedure for the preparation of compounds 5 and 12–15:
To a solution of 1,4-dihydropyridine, 4 or 8–11 (1 mmol) in anhy-
drous CH2Cl2 (10 mL) kept at 0 °C by means of an ice bath, were
sequentially added anhydrous TEA (2 equiv) and TFA (1.5 equiv).
The reaction mixture was then allowed to reach room temperature,
and was stirred for a further 5 h. After this time, the solvent was
evaporated, and the oil obtained was purified by column chroma-
tography (petroleum ether–ethyl acetate 4:1) to give compounds 5
or 12–15 as solids.
Acknowledgements
We acknowledge the PTRLI cycle III for a Grant to MFAA and
CIADS (University of Siena) for recording mass spectra and X-ray
diffractions.
References and notes
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cited therein; Vanden Eynde, J. J.; D’Orazio, P.; Mayence, A.; Maquestiau, A.
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7. Data deposited at the Cambridge Crystallographic Data Centre, CCDC 689300.
8. Data deposited at the Cambridge Crystallographic Data Centre, CCDC 689301.
N-(2,4-Dicyano-1,5-dimethyl-3-phenylcyclopenta-2,4-dienyl)-
20,20,20-trifluoroacetamide (5): yellow solid, 149 mg (45% yield),
mp 205–207 °C; dH (400 MHz, CDCl3) 1.62 (3H, s, CH3), 2.19 (3H,