Maleic Acid → N1-{4-[4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-trans-2-phenylcyclopropane-1-carboxamide, dimaleate salt

HRID 432420Notes

Reaction equation

HRID 432420 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:31]3[CH2:36][CH2:35][N:34]([CH:37]4[CH2:42][CH2:41][N:40]([CH3:43])[CH2:39][CH2:38]4)[CH2:33][CH2:32]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C@@H:20]4[CH2:22][C@H:21]4[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[O:19])=[C:13]([O:29][CH3:30])[CH:12]=3)[C:3]=12.[C:44]([OH:51])(=[O:50])/[CH:45]=[CH:46]\[C:47]([OH:49])=[O:48]>C(O)C>[C:44]([OH:51])(=[O:50])/[CH:45]=[CH:46]\[C:47]([OH:49])=[O:48].[C:44]([OH:51])(=[O:50])/[CH:45]=[CH:46]\[C:47]([OH:49])=[O:48].[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:31]3[CH2:32][CH2:33][N:34]([CH:37]4[CH2:42][CH2:41][N:40]([CH3:43])[CH2:39][CH2:38]4)[CH2:35][CH2:36]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C@@H:20]4[CH2:22][C@H:21]4[C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)=[O:19])=[C:13]([O:29][CH3:30])[CH:12]=3)[C:3]=12

Participants

4

Reactant 2

HCID 444266Maleic AcidHCID 20817142N1-{4-[4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-trans-2-phenylcyclopropane-1-carboxamide

Product 1

HCID 131724252N1-{4-[4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-trans-2-phenylcyclopropane-1-carboxamide, dimaleate saltYield 71.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

N1-{4-[4-Amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-trans-2-phenylcyclopropane-1-carboxamide (75 mg, 0.129 mmol) was dissolved in ethanol (2 mL) and maleic acid (45 mg, 0.387 mmol) in ethanol (1 mL) was added. The reaction mixture was stirred at room temperature for 5 hours. The solvent was removed and ethyl acetate was added and the solid was collected by filtration to give N1-{4-[4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-trans-2-phenylcyclopropane-1-carboxamide, dimaleate salt (75 mg). 1H NMR (DMSO-d6) δ 1.17 (m, 1H), 1.32 (m, 2H), 1.48 (m, 2H), 1.48, (m, 2H), 2.19 (m, 4H), 2.37 (M, 1H), 2.46 (m, 1H), 2.59 (m, 1H), 2.78 (s, 3H), 2.98-3.52 (bm, 9H), 3.90 (s, 3H), 5.02 (m, 1H), 6.08 (s, 4H), 7.17-7.33 (m, 7H), 8.25 (m, 2H), 9.65 (s, 1H). LCMS (Finigan-Column: Pecosphere, C18, 3 um, 33×4.6 mm. Eluents: 0% B/A to 100% B/A in 4 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 3.0 mL/min.): MH+ =581.4, Rt=1.77 min.

Workup

  1. customThe solvent was removed
  2. additionethyl acetate was added
  3. filtrationthe solid was collected by filtration

Sources & evidence

ORD record
ord-84fa890f35454977a25ffa8489ac8ddb
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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