Citric Acid → 4-Chloro-3-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-d]pyrimidine-6-amine

HRID 2408889Notes

Reaction equation

HRID 2408889 reaction equation
C(N(CC)CC)C.[NH2:8][C:9]1[N:14]=[C:13](Cl)[C:12]([C:16](=O)[CH2:17][CH:18]2[CH2:22][O:21][C:20]([CH3:24])([CH3:23])[O:19]2)=[C:11]([Cl:26])[N:10]=1.Cl.[CH3:28][O:29][C:30]1[CH:38]=[CH:37][C:33]([CH2:34][NH:35][NH2:36])=[CH:32][CH:31]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl>[Cl:26][C:11]1[N:10]=[C:9]([NH2:8])[N:14]=[C:13]2[N:35]([CH2:34][C:33]3[CH:37]=[CH:38][C:30]([O:29][CH3:28])=[CH:31][CH:32]=3)[N:36]=[C:16]([CH2:17][CH:18]3[CH2:22][O:21][C:20]([CH3:24])([CH3:23])[O:19]3)[C:12]=12

Participants

6

Reactant 4

HCID 311Citric AcidHCID 8471TriethylamineHCID 457893744-Methoxybenzylhydrazine hydrochlorideHCID 58201197HCID 58201197, compound

Product 1

HCID 582012174-Chloro-3-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-d]pyrimidine-6-amineYield 91.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triethylamine (83.68 ml) was added to a mixture composed of the above 1-(2-amino-4,6-dichloropyrimidin-5-yl)-2-(2,2-dimethyl-[1,3]dioxolan-4-yl)ethan-1-one (61.23 g), (4-methoxybenzyl)-hydrazine hydrochloride (41.50 g) produced by the method described in U.S. Patent No. US2003/18197, and dichloromethane (600 ml) over 30 minutes under cooling in an ice bath. Thereafter, while the temperature of the reaction solution was gradually raised, it was stirred for 17 hours. Thereafter, a 10% citric acid aqueous solution was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and was then concentrated under reduced pressure. A 5% citric acid aqueous solution was added to the resulting residue, and the precipitate was then collected by filtration. The resultant was washed with water, so as to obtain the title compound (73.84 g) as a solid.

Workup

  1. customproduced by the method
  2. temperatureThereafter, while the temperature of the reaction solution was gradually raised
  3. extractionfollowed by extraction with dichloromethane
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationwas then concentrated under reduced pressure
  6. additionA 5% citric acid aqueous solution was added to the resulting residue
  7. filtrationthe precipitate was then collected by filtration
  8. washThe resultant was washed with water

Sources & evidence

ORD record
ord-e65f5d96ff0747d9ba8c563274997a10
Source dataset
uspto-grants-2014_08
Patent number
US08815880B2

Reaction notes

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