Maleic Acid → HCID 178481005, compound

HRID 432184Notes

Reaction equation

HRID 432184 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C@@H:8]2[CH2:13][CH2:12][C@H:11]([N:14]3[C:18]4=[N:19][CH:20]=[N:21][C:22]([NH2:23])=[C:17]4[C:16]([C:24]4[CH:29]=[CH:28][C:27]([O:30][C:31]5[N:36]=[CH:35][CH:34]=[CH:33][N:32]=5)=[CH:26][CH:25]=4)=[N:15]3)[CH2:10][CH2:9]2)[CH2:4][CH2:3]1.[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]\[C:40]([OH:42])=[O:41]>C(O)C>[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]\[C:40]([OH:42])=[O:41].[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]\[C:40]([OH:42])=[O:41].[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]\[C:40]([OH:42])=[O:41].[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C@@H:8]2[CH2:13][CH2:12][C@H:11]([N:14]3[C:18]4=[N:19][CH:20]=[N:21][C:22]([NH2:23])=[C:17]4[C:16]([C:24]4[CH:25]=[CH:26][C:27]([O:30][C:31]5[N:32]=[CH:33][CH:34]=[CH:35][N:36]=5)=[CH:28][CH:29]=4)=[N:15]3)[CH2:10][CH2:9]2)[CH2:4][CH2:3]1

Participants

4

Reactant 2

HCID 444266Maleic AcidHCID 178481004HCID 178481004, compound

Product 1

HCID 178481005HCID 178481005, compoundYield 67.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A solution of cis-1-[4-(4-methylpiperazino)cyclohexyl]-3-[4-(2-pyrimidinyloxy)-phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (intermediate BD) (0.193 g, 0.0004 mol) in absolute ethanol (15 mL) was heated to reflux. A solution of maleic acid (0.184 g, 0.00159 mol) in absolute ethanol (10 mL) was heated to 78° C. was added and the mixture was heated at reflux for 10 minutes. The mixture was allowed to cool to room temperature, and the white precipitate which formed was collected by filtration and washed with absolute ethanol (2×10 mL). The residual solvent was removed in vacuo to give cis-1-[4-(4-methylpiperazino)cyclohexyl]-3-[4-(2-pyrimidinyloxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine tris maleate as a white solid (0.222 g, 0.00027 mol): 1H NMR (DMSO-d6, 400 MHz) 8.68 (d, 2H), 8.26 (s, 1H), 7.72 (d, 2H), 7.39 (d, 2H), 7.32 (t, 1H), 6.17 (s, 6H), 4.85-4.87 (m, 1H), 3.85-2.85 (br, 9H), 2.71 (s, 3H), 2.23-2.43 (bs, 2H), 2.03-2.18 (bs, 2H), 1.71-2.89 (bs, 4H)RP-HPLC (Delta Pak C18, 5 μm, 300 A, 15 cm; 5%-85% acetonitrile—0.1M ammonium acetate over 20 min, 1 mL/min) Rt 9.56 min. MS: MH+486.

Workup

  1. additionwas added
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 10 minutes
  4. customthe white precipitate which formed
  5. filtrationwas collected by filtration
  6. washwashed with absolute ethanol (2×10 mL)
  7. customThe residual solvent was removed in vacuo

Sources & evidence

ORD record
ord-55b4827904ee476795091c55b1520765
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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