1-((6-Fluoropyridin-2-yl)methyl)-N-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine → N-(1-methyl-1H-pyrazol-4-yl)-1-((6-(pyrrolidin-1-yl)pyridin-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine
Reaction equation
F[C:2]1[N:7]=[C:6]([CH2:8][N:9]2[C:13]3=[N:14][C:15]([NH:18][C:19]4[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=4)=[N:16][CH:17]=[C:12]3[CH:11]=[N:10]2)[CH:5]=[CH:4][CH:3]=1.O1CCOCC1.[NH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1>>[CH3:24][N:22]1[CH:23]=[C:19]([NH:18][C:15]2[N:14]=[C:13]3[N:9]([CH2:8][C:6]4[CH:5]=[CH:4][CH:3]=[C:2]([N:31]5[CH2:35][CH2:34][CH2:33][CH2:32]5)[N:7]=4)[N:10]=[CH:11][C:12]3=[CH:17][N:16]=2)[CH:20]=[N:21]1Participants
3
Conditions
- Temperature
- 160 °C
Procedure
1-((6-fluoropyridin-2-yl)methyl)-N-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine (Example 170) (45 mg, 0.138 mmol) was dissolved in dioxane/pyrrolidine (0.6 mL, 1:1) in a microwave tube under nitrogen. This was sealed and heated at 160° C. for 1 h. The mixture was concentrated in vacuo and re-dissolved in MeOH (2 mL). A solid precipitated over 16 h and was collected by filtration, and triturated with more MeOH to give N-(1-methyl-1H-pyrazol-4-yl)-1-((6-(pyrrolidin-1-yl)pyridin-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine as a white solid (17 mg, 33% yield). 1H NMR (d6-Acetone) δ 8.86 (s and br s, 2H), 8.05 (s, 1H), 7.98 (s, 1H), 7.60 (s, 1H), 7.35 (t, 1H), 6.28 (d, 1H), 6.18 (d, 1H), 5.47 (s, 2H), 3.82 (s, 3H), 3.38 (m, 4H), 1.95 (m, 4H); LC-MS method B, (ES+) 376.2, RT=4.95 min.