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H. Mukaiyama et al. / Bioorg. Med. Chem. 16 (2008) 909–921
5.1.22. 2-(3,5-Dimethoxyphenylamino)-7-((R)-1-hydroxy-
methyl-2-methylpropylamino)-5-isopropylpyrazolo[1,5-
a]pyrimidine-3-carboxamide (6g). The title compound
was prepared from 5g as described for the synthesis of
prepared from 5k as described for the synthesis of 6a
and obtained as an off-white solid (77%): mp 196–
28
D
197 ꢁC (MeOH); ½aꢁ ꢀ137.3ꢁ (c 1.05, DMSO); IR
(KBr) 3466, 1605, 1574, 1153 cmꢀ1
;
1H NMR
6a and obtained as an off-white solid (84%): mp 177–
(DMSO-d6) d 0.95–1.05 (4H, m), 1.85–1.95 (1H, m),
2.00–2.10 (4H, m), 3.49 (2H, t, J = 5.0 Hz), 3.74 (6H,
s), 3.85–4.00 (1H, m), 4.05–4.15 (1H, m), 4.84 (1H, t,
J = 5.4 Hz), 4.90–5.05 (1H, m), 6.06 (1H, t,
J = 2.2 Hz), 6.26 (1H, s), 6.77 (2H, d, J = 2.2 Hz), 7.31
(1H, d, J = 2.8 Hz), 7.60 (1H, d, J = 2.8 Hz), 9.59 (1H,
s). Anal. Calcd for C23H28N6O4Æ0.8H2O: C, 59.16; H,
6.39; N, 18.00. Found: C, 59.20; H, 6.28; N, 18.13.
28
178 ꢁC (MeOH); ½aꢁ ꢀ8.3ꢁ (c 1.09, DMSO); IR (KBr)
D
1
3381, 2964, 1649, 1585, 1154 cmꢀ1; H NMR (DMSO-
d6) d 0.95 (3H, d, J = 6.9 Hz), 0.99 (3H, d, J = 6.9 Hz),
1.26 (6H, d, J = 6.9 Hz), 1.95–2.10 (1H, m), 2.90–3.00
(1H, m), 3.60–3.75 (3H, m), 3.77 (6H, s), 4.99 (1H, t,
J = 5.0 Hz), 6.08 (1H, d, J = 2.2 Hz), 6.38 (1H, s), 6.87
(1H, d, J = 9.5 Hz), 6.93 (2H, d, J = 2.2 Hz), 7.40 (1H,
d, J = 2.8 Hz), 7.63 (1H, d, J = 2.8 Hz), 9.58 (1H, s).
Anal. Calcd for C23H32N6O4: C, 60.51; H, 7.06; N,
18.41. Found: C, 60.36; H, 7.04; N, 18.38.
5.1.27. 7-((S)-1-Benzyl-2-hydroxyethylamino)-5-cyclo-
propyl-2-(3,5-dimethoxyphenylaminopyrazolo[1,5-a]pyrim-
idine-3-carboxamide (6l). The title compound was
prepared from 5l as described for the synthesis of 6a
5.1.23. 5-Cyclopropyl-2-(3,5-dimethoxyphenylamino)-7-
((R)-1-hydroxymethyl-2-methylpropylamino)pyrazolo[1,5-
a]pyrimidine-3-carboxamide (6h). The title compound
was prepared from 5h as described for the synthesis of
and obtained as an off-white solid (quant.): mp 196–
28
197 ꢁC (MeOH); ½aꢁ ꢀ186.2ꢁ (c 1.06, DMSO); IR
D
1
(KBr) 3368, 1634, 1592, 1557 cmꢀ1; H NMR (DMSO-
d6) d 0.90–1.05 (4H, m), 1.95–2.05 (1H, m), 2.95 (1H,
dd, J = 13.6, 8.5 Hz), 3.03 (1H, dd, J = 13.6, 6.3 Hz),
3.55–3.65 (2H, m), 3.78 (6H, s), 4.00–4.10 (1H, m), 5.17
(1H, br s), 6.10 (1H, t, J = 2.2 Hz), 6.25 (1H, s), 6.90
(2H, d, J = 2.2 Hz), 7.04 (1H, d, J = 9.1 Hz), 7.17 (1H,
t, J = 7.6 Hz), 7.26 (2H, t, J = 7.6 Hz), 7.30–7.35 (3H,
m), 7.39 (1H, d, J = 2.5 Hz), 9.54 (1H, s). Anal. Calcd
for C27H30N6O4Æ0.5H2O: C, 63.39; H, 6.11; N, 16.43.
Found: C, 63.41; H, 5.81; N, 16.35.
6a and obtained as an off-white solid (89%): mp 204–
28
205 ꢁC (MeOH); ½aꢁ ꢀ2.4ꢁ (c 0.99, DMSO); IR (KBr)
D
1
3387, 1585, 1463, 1207 cmꢀ1; H NMR (DMSO-d6) d
0.95 (3H, d, J = 6.9 Hz), 0.99 (3H, d, J = 6.9 Hz), 1.00–
1.10 (4H, m), 1.95–2.15 (2H, m), 3.60–3.75 (3H, m),
3.76 (6H, s), 4.99 (1H, br s), 6.07 (1H, t, J = 2.2 Hz),
6.47 (1H, s), 6.81 (1H, d, J = 9.5 Hz), 6.91 (2H, d,
J = 2.2 Hz), 7.33 (1H, d, J = 2.2 Hz), 7.42 (1H, d,
J = 2.2 Hz), 9.58 (1H, s). Anal. Calcd for C23H30N6O4Æ-
H2O: C, 58.46; H, 6.83; N, 17.78. Found: C, 58.53; H,
6.69; N, 17.87.
5.1.28. 7-((R)-1-Benzyl-2-hydroxyethylamino)-5-cyclo-
propyl-2-(3,5-dimethoxyphenylamino)pyrazolo[1,5-a]pyrim-
idine-3-carboxamide (6m). The title compound was
prepared from 5m as described for the synthesis of 6a
5.1.24. 7-Amino-5-cyclopropyl-2-phenylaminopyrazolo[1,5-
a]pyrimidine-3-carboxamide (6i). The title compound
was prepared from 5i as described for the synthesis of
6a and obtained as an off-white solid (61%): mp 269–
270 ꢁC (MeOH; IR (KBr) 3304, 1649, 1597,
and obtained as an off-white solid (52%): mp 194–
28
195 ꢁC (MeOH); ½aꢁ +191.4ꢁ (c 1.05, DMSO); IR
D
1
(KBr) 3463, 1636, 1592, 1556 cmꢀ1; H NMR (DMSO-
d6) d 0.90–1.05 (4H, m), 1.95–2.05 (1H, m), 2.95 (1H,
dd, J = 13.6, 8.5 Hz), 3.03 (1H, dd, J = 13.6, 6.3 Hz),
3.55–3.65 (2H, m), 3.78 (6H, s), 4.00–4.10 (1H, m), 5.17
(1H, br s), 6.10 (1H, t, J = 2.2 Hz), 6.25 (1H, s), 6.90
(2H, d, J = 2.2 Hz), 7.04 (1H, d, J = 9.1 Hz), 7.17 (1H,
t, J = 7.6 Hz), 7.26 (2H, t, J = 7.6 Hz), 7.30–7.35 (3H,
m), 7.39 (1H, d, J = 2.5 Hz), 9.54 (1H, s). Anal. Calcd
for C27H30N6O4: C, 64.53; H, 6.02; N, 16.72. Found: C,
64.22; H, 6.01; N, 16.70.
1
1561 cmꢀ1; H NMR (DMSO-d6) d 0.95–1.05 (4H, m),
1.95–2.10 (1H, m), 6.13 (1H, s), 6.92 (1H, t,
J = 6.9 Hz), 7.26 (1H, br s), 7.30 (2H, t, J = 7.6 Hz),
7.43 (1H, br s), 7.74 (2H, d, J = 7.9 Hz), 7.82 (2H, br
s), 9.57 (1H, s). Anal. Calcd for C16H16N6O: C, 62.32;
H, 5.23; N, 27.26. Found: C, 62.01; H, 5.10; N, 27.08.
5.1.25. 5-Cyclopropyl-2-(3,5-dimethoxyphenylamino)-7-
((R)-2-hydroxymethylpyrrolidin-1-yl)pyrazolo[1,5-a]pyrim-
idine-3-carboxamide (6j). The title compound was pre-
pared from 5j as described for the synthesis of 6a and
5.1.29. 5-Cyclopropyl-2-(3,5-dimethoxyphenylamino)-7-
[(S)-2-hydroxy-1-(1H-indol-3-ylmethyl)ethylamino]pyraz-
olo[1,5-a]pyrimidine-3-carboxamide (6n). The title com-
pound was prepared from 5n as described for the
obtained as an off-white solid (88%): mp 197–198 ꢁC
28
(MeOH); ½aꢁ +136.8ꢁ (c 1.03, DMSO); IR (KBr)
D
1
3462, 1604, 1574, 1155 cmꢀ1; H NMR (DMSO-d6) d
0.95–1.05 (4H, m), 1.85–1.95 (1H, m), 2.00–2.10 (4H,
m), 3.49 (2H, t, J = 5.0 Hz), 3.74 (6H, s), 3.85–4.00
(1H, m), 4.05–4.15 (1H, m), 4.84 (1H, t, J = 5.4 Hz),
4.90–5.05 (1H, m), 6.06 (1H, t, J = 2.2 Hz), 6.26 (1H,
s), 6.77 (2H, d, J = 2.2 Hz), 7.31 (1H, d, J = 2.8 Hz),
7.60 (1H, d, J = 2.8 Hz), 9.59 (1H, s). Anal. Calcd for
C23H28N6O4Æ0.25H2O: C, 60.45; H, 6.29; N, 18.39.
Found: C, 60.49; H, 6.23; N, 18.45.
synthesis of 6a and obtained as an off-white solid (98%):
28
D
mp 250–251 ꢁC (MeOH); ½aꢁ ꢀ226.1ꢁ (c 1.03, DMSO);
IR (KBr) 3419, 1643, 1587, 1157 cmꢀ1
;
1H NMR
(DMSO-d6) d 0.80–1.00 (4H, m), 1.85–1.95 (1H, m),
3.06 (1H, dd, J = 14.8, 7.9 Hz), 3.15 (1H, dd, J = 14.8,
6.0 Hz), 3.65–3.70 (2H, m), 3.76 (6H, s), 4.00–4.15 (1H,
m), 5.15(1H, t, J = 5.0 Hz), 6.05–6.15 (2H, m), 6.90
(2H, d, J = 6.9 Hz), 6.95–7.10 (3H, m), 7.19 (1H, d,
J = 2.2 Hz), 7.25–7.35 (2H, m), 7.39 (1H, d, J = 2.2 Hz),
7.66 (1H, d, J = 8.2 Hz), 9.55 (1H, s), 10.80 (1H, br s).
Anal. Calcd for C29H31N7O4ÆH2O: C, 62.24; H, 5.94; N,
17.52. Found: C, 62.47; H, 5.76; N, 17.60.
5.1.26. 5-Cyclopropyl-2-(3,5-dimethoxyphenylamino)-7-
((S)-2-hydroxymethylpyrrolidin-1-yl)pyrazolo[1,5-a]pyrim-
idine-3-carboxamide (6k). The title compound was