992
J. Portilla et al. / Tetrahedron 68 (2012) 988e994
1H NMR (500 MHz,110 ꢀC):
d
¼2.29 (m, 2H, 7-CH2), 2.49 (s, 3H, CH3),
white solid in 85% yield; mp >300 ꢀC. FTIR:
O), 3119 (NeH) cmꢁ1. 1H NMR (400 MHz, 120 ꢀC):
n
¼1590 (C]N), 1664 (C]
¼2.09 (m, 2H, 6-
3.02 (t, J¼7.3 Hz, 2H, 6-CH2), 3.36 (t, J¼7.3 Hz, 2H, 8-CH2), 7.11 (s,1H,
d
3-H), 8.23 (d, J¼9.2 Hz, 2H, o-Ar), 8.27 (d, J¼9.2 Hz, 2H, m-Ar) ppm.
CH2), 2.35 (s, 3H, CH3eAr), 2.70 (t, J¼7.3 Hz, 2H, 7-CH2), 2.92 (t,
J¼7.3 Hz, 2H, 8-CH2), 6.53 (s, 1H, 3-H), 7.24 (d, J¼8.0 Hz, 2H, m-Ar),
7.85 (d, J¼8.0 Hz, 2H, o-Ar), 12.52 (s, 1H, 4-NH) ppm. 13C NMR
13C NMR (125 MHz, 110 ꢀC):
d¼21.0 (C-7), 21.6 (CH3), 28.6 (C-6),
28.8 (C-8), 92.6 (C-3), 122.5 (C-5a), 123.2 (Cm-Ar), 126.4 (Co-Ar),
139.0 (Ci-Ar), 147.0 (Cp-Ar), 147.5 (C-8a), 149.1 (C-3a), 151.7 (C-2),
156.0 (C-5) ppm. MS: (70 eV, EI) m/z (%)¼294 (100) [Mþ], 248 (12)
[Mꢁ46], 65 (18) [C5H5], 39 (32) [C3H3]. Elemental analysis calcd for
C16H14N4O2 (294.31): C, 65.30; H, 4.79; N, 19.04. Found: C, 65.33; H,
4.85; N, 19.06.
(100 MHz, 120 ꢀC):
d
¼21.1 (CH3eAr), 22.4 (6-CH2), 27.5 (7-CH2),
31.9 (5-CH2), 85.3 (C-3), 106.3 (C-7a), 126.5 (Co-Ar), 129.6 (Cm-Ar),
129.8 (Ci-Ar), 137.3 (Cp-Ar), 143.1 (C-3a), 152.3 (C-4a), 152.9 (C-2),
154.3 (C(8)]O) ppm. MS: (70 e, EI): m/z (%)¼265 (100) [Mþ], 65 (21)
[C5H5], 39 (14) [C3H3]. Elemental analysis calcd for C16H15N3O
(265.31): C, 72.43; H, 5.70; N, 15.84. Found: C, 72.45; H, 5.74; N,
15.88.
4.3. General procedure for the synthesis of 2-substituted-
4,5,6,7-tetrahydro-8H-cyclopenta[d]pyrazolo[1,5-a]pyrimidin-
8-ones 13aeh
4.3.5. 2-(4-Methoxyphenyl)-4,5,6,7-tetrahydro-8H-cyclopenta[d]
pyrazolo[1,5-a]pyrimidin-8-one (13e). This compound was isolated
A mixture of equimolar amounts of 3-substituted-5-amino-1H-
pyrazoles 1aeh (1 mmol) and 2-ethoxycarbonylcyclopentanone 11
(1 mmol) was thoroughly mixed at room temperature. The mixture
was heated in an oil-bath at 160 ꢀC for 2e3 min (see Scheme 3),
then cooled down to room temperature and the solid material
treated with ethanol (8 mL). The solvent was removed and the
products were recrystallized from ethanol to give compounds 13.
as white solid in 92% yield; mp >300 ꢀC. FTIR:
n
¼1262 (CeOCH3),
1599 (C]N), 1665 (C]O), 3120 (NeH) cmꢁ1
120 ꢀC):
.
1H NMR (400 MHz,
d
¼2.12 (m, 2H, 6-CH2), 2.73 (t, J¼7.4 Hz, 2H, 7-CH2), 2.92 (t,
J¼7.4 Hz, 2H, 5-CH2), 3.83 (s, 3H, OCH3), 6.34 (s, 1H, 3-H), 7.00 (d,
J¼8.2 Hz, 2H, m-Ar), 7.84 (d, J¼8.2 Hz, 2H, o-Ar), 11.86 (s, 1H, 4-NH)
13
ppm. C NMR (100 MHz, 120 ꢀC):
d¼21.2 (6-CH2), 26.3 (7-CH2),
30.7 (5-CH2), 54.7 (OCH3), 83.9 (C-3), 106.3 (C-7a), 113.7 (Cm-Ar),
125.2 (Ci-Ar), 126.8 (Co-Ar), 143.0 (C-3a), 152.2 (C-2), 152.7 (C-4a),
154.3 (C(8)]O), 159.4 (Cp-Ar) ppm. MS: (70 eV, EI) m/z (%)¼281
(100) [Mþ], 266 (9) [Mꢁ15], 252 (15) [Mꢁ29], 238 (24) [Mꢁ29], 65
(16) [C5H5], 39 (12) [C3H3]. Elemental analysis calcd for C16H15N3O2
(281.31): C, 68.31; H, 5.37; N, 14.94. Found: C, 68.34; H, 5.41; N,
14.95.
4.3.1. 2-Methyl-4,5,6,7-tetrahydro-8H-cyclopenta[d]pyrazolo[1,5-a]
pyrimidin-8-one (13a). This compound was isolated as white solid
in 92% yield; mp 286e288 ꢀC. FTIR:
n
¼1580 (C]N), 1667 (C]O), 3125
(NeH) cmꢁ1. 1H NMR (400 MHz, 27 ꢀC):
d
¼2.04 (m, 2H, 6-CH2), 2.25
(s, 3H, 2-CH3), 2.64 (t, J¼7.3 Hz, 2H, 7-CH2), 3.06 (t, J¼7.3 Hz, 2H, 5-
CH2), 5.89 (s, 1H, 3-H), 12.29 (s, 1H, 4-NH) ppm. 13C NMR (100 MHz,
27 ꢀC):
d
¼14.6 (2-CH3), 22.2 (6-CH2), 27.9 (7-CH2), 30.0 (5-CH2),
4.3.6. 2-(4-Chlorophenyl)-4,5,6,7-tetrahydro-8H-cyclopenta[d]pyr-
88.0 (C-3), 106.7 (C-7a), 143.2 (C-3a), 151.8 (C-4a), 153.8 (C-2), 155.3
(C-8, C]O) ppm. MS: (70 eV, EI): m/z (%)¼189 (100) [Mþ], 174 (6)
[Mꢁ15], 65 (43) [C5H5], 39 (51) [C3H3]. Elemental analysis calcd for
C10H11N3O (189.21): C, 63.48; H, 5.86; N, 22.21. Found: C, 63.51; H,
5.91; N, 22.23.
azolo[1,5-a]pyrimidin-8-one (13f). This compound was isolated as
white solid in 82% yield; mp >330 ꢀC. FTIR:
n
¼1594 (C]N), 1664 (C]
O), 3121 (NeH) cmꢁ1. 1H NMR (400 MHz, 120 ꢀC):
d
¼2.11 (m, 2H, 6-
CH2), 2.73 (t, J¼7.3 Hz, 2H, 7-CH2), 2.92 (t, J¼7.3 Hz, 2H, 5-CH2), 6.43
(s, 1H, 3H), 7.46 (d, J¼8.3 Hz, 2H, m-Ar), 7.92 (d, J¼8.3 Hz, 2H, o-Ar),
12.18 (s, 1H, 4-NH) ppm. 13C NMR (100 MHz, 120 ꢀC):
d¼21.2 (C-6),
4.3.2. 2-(tert-Butyl)-4,5,6,7-tetrahydro-8H-cyclopenta[d]pyrazolo
[1,5-a]pyrimidin-8-one (13b). This compound was isolated as white
26.3 (C-7), 30.8 (C-5), 84.6 (C-3), 106.4 (C-7a), 127.2 (Cm-Ar), 127.9
(Co-Ar), 131.5 (Ci-Ar), 132.7 (Cp-Ar), 143.5 (C-3a), 151.1 (C-2), 153.4
(C-4a), 154.2 (C-8, C]O) ppm. MS: (70 eV, EI) m/z (%)¼287/285 (41/
100) [Mþ], 258/256 (14/60) [Mꢁ29], 65 (25) [C5H5], 39 (19) [C3H3].
Elemental analysis calcd for C15H12ClN3O (285.73): C, 63.05; H,
4.23; N, 14.71. Found: C, 63.09; H, 4.25; N, 14.75.
solid in 83% yield; mp >330 ꢀC. FTIR:
n
¼1587 (C]N), 1678 (C]O),
3120 (NeH) cmꢁ1. 1H NMR (400 MHz, 120 ꢀC):
d
¼1.30 (s, 9H, t-Bu),
2.07 (m, 2H, 6-CH2), 2.67 (t, J¼7.3 Hz, 2H, 7-CH2), 2.87 (t, J¼7.3 Hz,
2H, 5-CH2), 5.87 (s, 1H, 3-H), 11.69 (s, 1H, 4-NH) ppm. 13C NMR
(100 MHz, 120 ꢀC):
d
¼21.9 (6-CH2), 27.0 (7-CH2), 31.3 (5-CH2), 30.1
(C(CH3)3), 32.3 (C(CH3)3), 84.1 (C-3),106.6 (C-7a),142.8 (C-3a),153.0
(C-4a), 155.1 (C-8, C]O), 164.2 (C-2) ppm. MS: (70 eV, EI): m/z (%)¼
231 (70) [Mþ], 216 (100) [Mꢁ15], 189 (46) [Mꢁ42], 65 (18) [C5H5],
39 (20) [C3H3]. Elemental analysis calcd for C13H17N3O (231.29): C,
67.51; H, 7.41; N, 18.17. Found: C, 67.55; H, 7.46; N, 18.16.
4.3.7. 2-(4-Bromophenyl)-4,5,6,7-tetrahydro-8H-cyclopenta[d]pyr-
azolo[1,5-a]pyrimidin-8-one (13g). This compound was isolated as
white solid in 90% yield; mp >300 ꢀC. FTIR:
n
¼1591 (C]N), 1665 (C]
O), 3123 (NeH) cmꢁ1. 1H NMR (400 MHz,,120 ꢀC):
d¼2.12 (m, 2H, 6-
CH2), 2.74 (t, J¼7.3 Hz, 2H, 7-CH2), 2.93 (t, J¼7.3 Hz, 2H, 5-CH2), 6.45
(s, 1H, 3H), 7.61 (d, J¼8.5 Hz, 2H, m-Ar), 7.87 (d, J¼8.5 Hz, 2H, o-Ar),
4.3.3. 2-Phenyl-4,5,6,7-tetrahydro-8H-cyclopenta[d]pyrazolo[1,5-a]
pyrimidin-8-one (13c). This compound was isolated as white solid
12.02 (s, 1H, 4-NH) ppm. 13C NMR (100 MHz, 120 ꢀC):
d¼21.2 (C-6),
26.3 (C-7), 30.7 (C-5), 84.5 (C-3), 106.5 (C-7a), 121.1 (Ci-Ar), 127.4
(Co-Ar), 130.8 (Cm-Ar), 131.8 (Cp-Ar), 143.1 (C-3a), 151.2 (C-2), 153.1
(C-4a), 154.2 (C-8, C]O) ppm. MS: (70 eV, EI) m/z (%)¼331/329 (99/
100) [Mþ], 302/300 (29/28) [Mꢁ29], 65 (45) [C5H5], 39 (28) [C3H3].
Elemental analysis calcd for C15H12BrN3O (330.18): C, 54.56; H,
3.66; N, 12.73. Found: C, 54.60; H, 3.72; N, 12.75.
in 92% yield; mp >330 ꢀC. FTIR:
n
¼1591 (C]N), 1668 (C]O), 3130
(NeH) cmꢁ1
.
1H NMR (400 MHz, 120 ꢀC):
d
¼2.12 (m, 2H, 6-CH2),
2.75 (t, J¼7.3 Hz, 2H, 7-CH2), 2.93 (t, J¼7.3 Hz, 2H, 5-CH2), 6.43 (s,
1H, 3-H), 7.38 (t, J¼7.5 Hz, 1H, p-Ph), 7.44 (t, J¼7.5 Hz, 2H, m-Ph),
7.93 (d, J¼7.4 Hz, 2H, o-Ph), 11.94 (s, 1H, 4-NH) ppm. 13C NMR
(125 MHz, 120 ꢀC):
d
¼21.2 (6-CH2), 26.3 (7-CH2), 30.7 (5-CH2), 84.4
(C-3), 106.4 (C-7a), 126.6 (C-o), 128.8 (C-p), 128.9 (C-m), 132.6 (C-i),
143.0 (C-3a), 152.3 (C-2), 152.9 (C-4a), 154.2 (C(8)]O) ppm. MS:
(70 eV, EI): m/z (%)¼251 (100) [Mþ], 222 (46) [Mꢁ29], 65 (41)
[C5H5], 39 (31) [C3H3]. Elemental analysis calcd for C15H13N3O
(251.28): C, 71.70; H, 5.21; N, 16.72. Found: C, 71.69; H, 5.23; N,
16.73.
4.3.8. 2-(4-Nitrophenyl)-4,5,6,7-tetrahydro-8H-cyclopenta[d]pyr-
azolo[1,5-a]pyrimidin-8-one (13h). This compound was isolated as
pale yellow solid in 86% yield; mp >330 ꢀC. FTIR:
n
¼1587 (C]N),
1662 (C]O), 3117 (NeH) cmꢁ1
;
1H NMR (400 MHz,, 100 ꢀC):
d
¼2.11
(m, 2H, 6-CH2), 2.73 (t, J¼7.3 Hz, 2H, 7-CH2), 2.94 (t, J¼7.3 Hz, 2H, 5-
CH2), 6.61 (s, 1H, 3H), 8.18 (d, J¼8.2 Hz, 2H, o-Ar), 8.25 (d, J¼8.2 Hz,
13
2H, m-Ar), 11.90 (s, 1H, 4-NH) ppm. C NMR (100 MHz, 100 ꢀC):
4.3.4. 2-(4-Methylphenyl)-4,5,6,7-tetrahydro-8H-cyclopenta[d]pyr-
azolo[1,5-a]pyrimidin-8-one (13d). This compound was isolated as
d
¼21.8 (C-6), 26.9 (C-7), 31.5 (C-5), 94.2 (C-3), 107.1 (C-7a), 123.7
(Cm-Ar), 125.9 (Co-Ar), 138.9 (Ci-Ar), 144.2 (C-3a), 147.6 (Cp-Ar),