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

HRID 594985Notes

Reaction equation

HRID 594985 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]1

Participants

3

Reactant 2

HCID 667652621-((6-Fluoropyridin-2-yl)methyl)-N-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amineHCID 86671735Dioxane pyrrolidine

Product 1

HCID 68376706N-(1-methyl-1H-pyrazol-4-yl)-1-((6-(pyrrolidin-1-yl)pyridin-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amineYield 33%

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.

Workup

  1. customThis was sealed
  2. concentrationThe mixture was concentrated in vacuo
  3. dissolutionre-dissolved in MeOH (2 mL)
  4. customA solid precipitated over 16 h
  5. filtrationwas collected by filtration
  6. customtriturated with more MeOH

Sources & evidence

ORD record
ord-d4aa9a6d927c4c86bea67278e2927b51
Source dataset
uspto-grants-2016_01
Patent number
US09242987B2

Reaction notes

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