4-Methoxypiperidine → 4-(2-hydroxypropan-2-yl)-N-(7-(4-methoxypiperidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)benzamide
Reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9](C)[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[CH:3]=1.[CH3:25][O:26][CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1>CN1C(=O)CCC1.CS(C)=O.CO>[OH:23][C:20]([C:17]1[CH:18]=[CH:19][C:14]([C:13]([NH:12][C:4]2[CH:3]=[C:2]([N:30]3[CH2:31][CH2:32][CH:27]([O:26][CH3:25])[CH2:28][CH2:29]3)[N:7]3[N:8]=[CH:9][CH:10]=[C:6]3[N:5]=2)=[O:24])=[CH:15][CH:16]=1)([CH3:21])[CH3:22]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 3
Procedure
A solution of N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2D, 50 mg, 0.151 mmol) and 4-methoxypiperidine (27 mg, 0.302 mmol) in NMP (0.950 mL) was stirred at 85° C. overnight. After cooling to room temperature, the mixture was diluted with a few drops of DMSO and methanol, and was then purified by preparatory HPLC, 5-95% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (16 mg, 26%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.45 (s, 6H) 1.59-1.75 (m, 2H) 1.98-2.12 (m, 2H) 3.31 (s, 3H) 3.41-3.58 (m, 3H) 3.97-4.15 (m, 2H) 6.35 (d, J=2.27 Hz, 1H) 7.40 (s, 1H) 7.60 (m, J=8.34 Hz, 2H) 7.99 (m, J=8.59 Hz, 2H) 8.08 (d, J=2.27 Hz, 1H) 10.88 (s, 1H). ESI-MS: m/z 410.3 (M+H)+.
Workup
- customwas then purified by preparatory HPLC, 5-95% (MeCN/H2O gradient+0.01% TFA)
Sources & evidence
- ORD record
- ord-da8f5f29528d4265a5ce120bae4dc323
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08921358B2
Reaction notes
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