Benzoyl chloride → HCID 178488212, compound

HRID 432170Notes

Reaction equation

HRID 432170 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[N:14][C:15]=3[NH2:17])[N:10]([CH:18]3[CH2:23][CH2:22][CH:21]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:20][CH2:19]3)[N:9]=2)=[CH:4][C:3]=1[O:31][CH3:32].[C:33](Cl)(=[O:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>ClCCl>[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([C@H:18]3[CH2:23][CH2:22][C@H:21]([N:24]4[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]4)[CH2:20][CH2:19]3)[N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:33](=[O:40])[C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[C:3]([O:31][CH3:32])[CH:4]=3)[C:16]=12

Participants

4

Reactant 2

HCID 7412Benzoyl chlorideHCID 208170343-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)-cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 178488212HCID 178488212, compoundYield 63.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)-cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Intermediate AP) (0.31 g, 0.00071 mol) and benzoyl chloride (0.105 g, 0.00075 mol) in anhydrous dichloromethane (10 mL) N-ethyl-N,N-diisopropylamine (0.11 g, 0.00085 moL) was added dropwise over a 5 min. period. The stirring under nitrogen was continued for an additional 4 hours, the solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate (30 mL) and water (25 mL). The organic phase was dried with magnesium sulfate and concentrated under the reduced pressure to yield a yellow oil which was purified by flash column chromatography on silica using dichloromethane/triethylamine/methanol (94:5:1) as a mobile phase to give trans-N-{4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl}benzamide as a white solid (0.250 g, 0.00045 mol). It was dissolved in refluxing ethanol (17 mL) and a preheated solution of maleic acid (0.155 g, 0.00133 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 trans—N-{4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl }-2-methoxyphenyl}benzamide dimaleate as a white solid (0.196 g, 0.000254 mol):

Workup

  1. customthe solvent was removed under reduced pressure
  2. customthe residue was partitioned between ethyl acetate (30 mL) and water (25 mL)
  3. dry with materialThe organic phase was dried with magnesium sulfate
  4. concentrationconcentrated under the reduced pressure
  5. customto yield a yellow oil which
  6. customwas purified by flash column chromatography on silica

Sources & evidence

ORD record
ord-b783419d925b4e3791987058479baaa4
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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