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5.2.5.2. 6, 7-Dihydro-N-(5-methyl-1H-pyrazol-3-yl)-2-(4-
methylpiperidin-1-yl)-5H-cyclopenta[d]pyrimidin-4-amine (14b).
Grey Solid: Yield 58%, mp 226e228 ꢀC. 1H NMR (300 Hz, DMSO-d6):
0.89e1.03 (m, 5H, piperdineeCH2), and epipeidineeCH2), 1.61 (d,
5.2.5.8. Ethyl 1-(4-(5-tert-butyl-1H-pyrazol-3-ylamino)-6,7-
dihydro-5H-cyclopenta[d]pyrimidin-2-yl)piperidine-3-carboxylate
(15d). Off white Solid: Yield 65%, mp 251e252 ꢀC. 1H NMR (300 Hz,
d
CDCl3):
d
1.26 (t, 3H, J ¼ 6.9 Hz. e ethyleCH2), 1.35 (s, 9H, t-butyl
2H, J ¼ 10.8 Hz, -methylpiperidine- CH2)), 1.91 (brs, 2H, cyclo-
pentyleCH2), 2.60e2.63 (m, 4H, cyclopentyleCH2), 2.76 (t, 2H,
J ¼ 12.5 Hz, -methylpiperidineeCH2), 4.56 (d, 2H, J ¼ 12.3 Hz,
methylpiperidineeCH2), 6.32 (s, 1H, pyrazole -H), 8.66 (s, 1H, pyr-
azole-NH), 11.86 (s, 1H, pyrimidineeNH). HRMS calcd for C17H25N6
[MþH] þ: 313.2135, found 313.2112; HPLC Retention time e
3.45 min, Purity e 99.23%.
eCH3), 1.56e1.69 (m, 2H, piperidineeCH2), 1.73e1.83 (m, 2H,
piperidine eCH2), 2.04e2.12 (m, 2H, cyclopentyleCH2), 2.54e2.60
(m, 1H, piperidineeCH), 2.64e2.69 (m, 2H, cyclopentyleCH2),
2.78e2.86 (m, 2H, cyclopentyl-CH2), 3.02e3.10 (m, 1H, piper-
idineeCH2), 3.21e3.28 (m, 1H, piperidineeCH2), 4.15 (q, 2H, J ¼ ,
ethyleCH2), 4.50 (d, 1H, J ¼ 12.9 Hz, piperidine-CH2), 4.75 (d, 1H,
J ¼ 11.4 Hz, piperidineeCH2), 6.44 (brs, 1H, pyrazoleeH), 6.65 (s, 1H,
pyrazoleeNH). HRMS calcd. for C22H33N6O2 [MþH]þ: 413.2660;
found 413.2657; HPLC Retention time e 5.06 min, Purity e 98.92%.
5.2.5.3. 2-(azepan-1-yl)-6,7-dihydro-N-(5-methyl-1H-pyrazol-3-yl)-
5H-cyclopenta[d]pyrimidin-4-amine (14c). Off White Solid: Yield
35%, mp 233e234 ꢀC. 1H NMR (300 Hz, DMSO-d6):
d
1.46 (brs, 4H,
5.2.5.9. N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(4-methylpiperidin-1-
azepaneeCH2), 1.70 (brs, 4H, azepaneeCH2), 1.90e1.92 (m, 2H,
cyclopentyleCH2), 2.19 (s, methylpyrazoleeCH3), 2.57e2.66 (m, 4H,
cyclopentyleCH2), 3.66 (t, 4H, J ¼ 5.4 Hz, -azepaneeCH2), 6.44 (s,
1H, pyrazoleeH), 8.60 (s, 1H, pyrazoleeNH), 11.84 (s, 1H, pyr-
imidineeNH). HPLC Retention time e 4.31 min, Purity e 95.41%.
yl)-5,6,7,8-tetrahydro-5,8-methanoquinazolin-4-amine
Brown Solid: Yield 74%, mp 237.1e238 ꢀC. 1H NMR (300 Hz, CDCl3):
0.75 (brs, 2H, cyclopentyleCH2), 0.97e0.99 (5H, m, piper-
idineeCH3 and cycloropyleCH2), 1.20e1.27 (m, 4H, piper-
idineeCH2), 1.49 (m, 1H, piperidineeCH), 1.72e1.75 (m, 4H,
camphoreCH2), 1.91 (m, 3H, -piperdine - CH and e camphoreCH2),
2.89 (t, 2H, J ¼ 12.3 Hz, camphoreCH), 3.23 (d, 2H, J ¼ 17.1 Hz,
piperidineeCH), 4.62 (d, J ¼ 12.0 Hz, piperidineeCH), 5.94 (s, 1H,
pyrazoleeNH), 6.21 (s, 1H, pyrazoleeH). HRMS calcd for C21H29N6
[MþH]þ: 365.2448, found 365.2443; HPLC Retention time e
5.43 min, Purity e 99.59%.
(36).
d
e
5.2.5.4. Ethyl 1-(4-(5-methyl-1H-pyrazol-3-ylamino)-6,7-dihydro-
5H-cyclopenta[d]pyrimidin-2-yl)piperidine-3-carboxylate
(14d).
Brown Solid: Yield 62%, mp 238e239 ꢀC. 1H NMR (300 Hz, DMSO-
d6):
d
Yield ¼ 35%. 1H NMR (300 Hz, DMSO-d6):
d 1.46 (brs, 4H,
azepaneeCH2), 1.70 (brs, 4H, azepaneeCH2), 1.90e -1.92 (m, 2H,
cyclopentyleCH2), 2.19 (s, methylpyrazoleeCH3), 2.57e2.66 (m, 4H,
cyclopentyleCH2), 3.66 (t, 4H, J ¼ 5.4 Hz, -azepaneeCH2), 6.44 (s,
1H, pyrazoleeH), 8.60 (s, 1H, pyrazoleeNH), 11.84 (s, 1H, pyr-
imidineeNH). HRMS calcd for C19H27N6 O2[MþH]þ: 371.2190,
found 371.2173 5516e02; HPLC Retention time e 3.58 min, Purity -
95.41%.
5.2.5.10. N-(5-cyclopropyl-1H-pyrazol-3-yl)-7,7-difluoro-6,7-
dihydro-2-(4-methylpiperidin-1-yl)-5h-cyclopenta[d]pyrimidin-4-
amine (37). Yellow Solid: Yield 79%, mp 225e226.1 ꢀC. 1H NMR
(300 Hz, DMSO-d6):
d 0.65 (brs, 2H, cyclopopyl-CH2), 0.91e0.96 (m,
5H, piperidineeCH3 and e cyclopropyleCH2), 1.02e1.06 (m, 2H,
piperidineeCH2), 1.34 (brs, 1H, piperidineeCH), 1.63e1.66 (m, 2H,
piperidineeCH2), 1.88e1.91 (m, 1H, cyclopropyleCH), 2.70e2.73
(m, 3H, cyclopropyleCH2 and e piperidineeCH2), 2.80e2.89 (m, 3H,
cyclopropyl eCH2 and e piperidineeCH2), 4.56 (d, J ¼ 12.3 Hz,
piperidine eCH2), 6.27 (s, 1H, pyrazoleeH), 9.43 (s, 1H, pyr-
azoleeNH), 12.12 (s, 1H, pyrimidineeNH). HRMS calcd for
5.2.5.5. N-(5-tert-butyl-1H-pyrazol-3-yl)-6,7-dihydro-2-(piperidin-
1-yl)-5h-cyclopenta[d]pyrimidin-4-amine (15a). White Solid: Yield
59%, mp 237e239.3 ꢀC. 1H NMR (300 Hz, DMSO-d6):
d 1.26 (s, 9H, t-
butyl eCH3),1.47 (bs, 4H, piperidineeCH2), 1.60e1.61 (m, 2H,
piperidineeCH2), 1.90e1.93 (m, 2H, cyclopentyleH2), 2.59e2.66 (m,
4H, cyclopentyleCH2), 3.67e3.69 (m, 4H, piperidineeCH2), 6.55 (s,
1H, pyrazoleeH), 8.76 (s, 1H, pyrazoleeNH), 11.91 (s, 1H, pyr-
imidineeNH). HRMS calcd. for C19H27N6 O2[MþH]þ: 341.2448;
found 341.2415; HPLC Retention time e 4.38 min, Purity e 99.23%.
C
19H25F2N6 [MþH]þ: 375.2123, found 375.2088; HPLC Retention
time e 6.41 min, Purity e 97.37%.
5.2.5.11. N-(5-cyclopropyl-1H-pyrazol-3-yl)-6,7-dihydro-7,7-
dimethyl-2-(4-methylpiperidin-1-yl)-5h-cyclopenta[d]pyrimidin-4-
amine (38). Grey Solid: Yield 79%, mp 228e230.1 ꢀC. 1H NMR
5.2.5.6. N-(5-tert-butyl-1H-pyrazol-3-yl)-6,7-dihydro-2-(4-
methylpiperidin-1-yl)-5h-cyclopenta[d]pyrimidin-4-amine
Off White Solid: Yield 82%, mp 241e242.2 ꢀC. 1H NMR (500 Hz,
DMSO):
0.89e0.91 (d, 2H, J ¼ 6 Hz, piperidineeCH3), 0.102e0.04
(15b).
(300 Hz, CDCl3): d 0.74e0.76 (m, 2H, cyclopropyleCH2), 0.94e0.98
(m, 5H, cyclopropyl - CH2 and e piperidineeCH3), 1.20 (s, 6H,
cyclopentyleCH3), 1.22e1.27 (m, 2H, piperidineeCH2), 1.69e1.73
(m, 3H, piperidine - CH2 and e piperidine eCH), 1.91e1.95 (m,
cyclopentyl eCH2 and e cyclopropyleCH), 2.57 (t, 2H, J ¼ 6.9 Hz,
cyclopentyleCH2), 2.89 (t, 2H, J ¼ 12 Hz, piperidineeCH2), 4.68 (d,
2H, J ¼ 12.9 Hz, piperidineeCH2), 5.92 (s, 1H, pyrazoleeH), 6.50 (s,
1H, pyrazoleeNH). HRMS calcd. for C21H31N6 [MþH]þ: 367.2605;
found 367.2611; HPLC Retention time e 7.32 min, Purity e 99.33%.
d
(m, 2H, piperidine e CH2), 1.26 (s, 9H, t-Butyl eCH3), 1.60 (d, 3H,
piperidine e CH and e piperidineeCH2), 1.90e1.93 (m, 2H, cyclo-
pentyl eCH2), 2.59e2.66 (m, 4H, cyclopentyleCH2), 2.78 (t, 2H,
J ¼ 12 Hz, piperidine e CH2), 5.58 (d, 2H, J ¼ 13 Hz, piperidine e
CH2), 6.44 (s, 1H, pyrazoleeH), 8.77 (s, 1H, pyrazoleeNH), 11.91 (s,
1H, Pyrimidine-NH). HRMS calcd for C20H31N6 [MþH] þ: 355.2605,
found 355.2606; HPLC Retention time e 4.31 min, Purity e 98.61%.
5.2.5.12. N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(4-methylpiperidin-
1-yl)-5,6-dihydrospiro[cyclopenta[d]pyrimidine-7,1'-cyclopentan]-4-
amine (39). White Solid: Yield 32%, mp 235e237. 1H NMR (300 Hz,
5.2.5.7. N-(5-tert-butyl-1H-pyrazol-3-yl)-2-(azepan-1-yl)-6,7-
dihydro-5h-cyclopenta[d]pyrimidin-4-amine (15c). Brown Solid:
Yield 62%, mp 246e247 ꢀC. 1H NMR (300 Hz, CDCl3):
d
1.27 (brs, 4H,
CDCl3): d 0.76 (brs, 2H, cyclopentyleCH2), 0.96 (s, 3H, piper-
-azepane-CH2), 1.35 (s, 9H, t-butylpyrazole-CH3), 1.84 (brs, 4H,
azepaneeCH2), 2.06e2.11 (m, 2H, cyclopentyleCH2), 2.67 (t, 2H,
J ¼ 6.6 Hz, cyclopentyleCH2), 2.81 (t, 2H, J ¼ 7.5 Hz, cyclo-
entyleCH2), 3.78 (t, 4H, J ¼ 5.4 Hz, azepaneeCH2), 6.38 (s, 1H,
pyrazole -H), 6.62 (s, 1H, pyrazoleeNH). HRMS calcd. for
idineeCH3), 0.98 (brs, 2H, cyclopropyleCH2), 1.58e1.73 (m, 7H,
cyclopentyl -CH2 and - piperidineeCH), 1.90e2.00 (m, 7H, cyclo-
pentyl e CH2 and e cyclopropyleCH), 2.56 (t, 2H, J ¼ 6.6 Hz,
cyclopentyleCH2), 2.88 (t, 2H, J ¼ 12.3 Hz, piperidineeCH2), 4.65 (d,
2H, J ¼ 12.6 Hz, piperidineeCH2), 5.90 (brs, 1H, pyrazoleeH), 6.50
(s, 1H, pyrazoleeNH). HRMS calcd. for C21H31N6 [MþH]þ: 393.2761;
found 393.2755; HPLC Retention time e 5.94 min, Purity e 95.02%.
C
16H31N6O3 [MþH]þ: 355.2452; found 355.2487; HPLC Retention
time e 4.29 min, Purity e 97.76%.