Maleic Acid → HCID 178488233, compound

HRID 897488Notes

Reaction equation

HRID 897488 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:30]3[CH2:35][CH2:34][C@@H:33]([N:36]4[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]4)[CH2:32][CH2:31]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:27])[O:19][CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[C:13]([O:28][CH3:29])[CH:12]=3)[C:3]=12.[C:43]([OH:50])(=[O:49])/[CH:44]=[CH:45]\[C:46]([OH:48])=[O:47]>C(O)C>[C:43]([OH:50])(=[O:49])/[CH:44]=[CH:45]\[C:46]([OH:48])=[O:47].[C:43]([OH:50])(=[O:49])/[CH:44]=[CH:45]\[C:46]([OH:48])=[O:47].[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:30]3[CH2:31][CH2:32][C@@H:33]([N:36]4[CH2:37][CH2:38][N:39]([CH3:42])[CH2:40][CH2:41]4)[CH2:34][CH2:35]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:27])[O:19][CH2:20][C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)=[C:13]([O:28][CH3:29])[CH:12]=3)[C:3]=12

Participants

4

Reactant 2

HCID 444266Maleic AcidHCID 178488232HCID 178488232, compound

Product 1

HCID 178488233HCID 178488233, compoundYield 77.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of benzyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl]carbamate (2.00 g, 0.0052 mol), cis-3-iodo-1-[4-(4-methylpiperazino)-cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (1.92 g, 0.0044 mol), tetrakis-(triphenylphosphine)palladium (0.300 g, 0.00026 mol) and sodium carbonate (1.35 g, 0.0109 mol) was heated in a mixture of ethylene glycol dimethyl ether (70 mL) and water (35 mL) at 80° C. for sixteen hours under an atmosphere of nitrogen. The mixture was allowed to cool to ambient temperature and solvents were removed under reduced pressure. The residue was partitioned between saturated aqueous sodium bicarbonate solution (150 mL) and ethyl acetate (180 mL), the organic layer separated and the aqueous layer further extracted twice with ethyl acetate (250 mL each). The combined organic extracts were dried over magnesium sulfate. The solvents were evaporated under reduced pressure to leave a tan solid which was purified by flash column chromatography on silica using dichloromethane/triethylamine/methanol (96:3:1) as a mobile phase to give cis-benzyl N-{4-{4-amino-1-[4-(4-methylpiperazino)-cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl}carbamate as a white solid (1.88 g, 0.0023 mol). Cis-benzyl N-{4-{4-amino-1-[4-(4-methylpiperazino)-cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl}carbamate (0.206 g, 0.00036 mol) was dissolved in refluxing ethanol (17 mL) and a preheated solution of maleic acid (0.126 g, 0.00108 mol) in ethanol (8 mL) was added. The mixture was refluxed for 10 min, cooled to ambient temperature and the precipitate collected by filtration, washed with ethyl acetate and dried to give cis-benzyl N-{4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl}-carbamate dimaleate as a white solid (0.224 g, 0.00028 mol):

Workup

  1. temperatureThe mixture was refluxed for 10 min
  2. filtrationthe precipitate collected by filtration
  3. washwashed with ethyl acetate
  4. customdried

Sources & evidence

ORD record
ord-484e58c13c094c7f822bb7b941985208
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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