1,4-Dioxane hydrochloride → 3-((3,5-dimethoxyphenyl)ethynyl)-1-(pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 516141Notes

Reaction equation

HRID 516141 reaction equation
Cl.O1CCOCC1.[NH2:8][C:9]1[N:14]=[CH:13][N:12]=[C:11]2[N:15]([CH:30]3[CH2:34][CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31]3)[N:16]=[C:17]([C:18]#[C:19][C:20]3[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[C:22]([O:28][CH3:29])[CH:21]=3)[C:10]=12>>[CH3:27][O:26][C:24]1[CH:25]=[C:20]([C:19]#[C:18][C:17]2[C:10]3[C:11](=[N:12][CH:13]=[N:14][C:9]=3[NH2:8])[N:15]([CH:30]3[CH2:34][CH2:33][NH:32][CH2:31]3)[N:16]=2)[CH:21]=[C:22]([O:28][CH3:29])[CH:23]=1

Participants

3

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 89870803tert-butyl 3-(4-amino-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidine-1-carboxylate

Product 1

HCID 898707833-((3,5-dimethoxyphenyl)ethynyl)-1-(pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 127.5%

Procedure

4N-Hydrochloric acid/1,4-dioxane (4 ml) was added to the tert-butyl 3-(4-amino-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidine-1-carboxylate (32 mg) obtained in Step 3, and the mixture was stirred at room temperature for 1.5 hours. After distilling the solvent of the resulting reaction mixture off under reduced pressure, toluene azeotropic distillation was subsequently performed to obtain a crude product of 3-((3,5-dimethoxyphenyl)ethynyl)-1-(pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (32 mg). Chloroform (2.0 ml) and triethylamine (20 μl) were added to a portion of the resulting crude product (12 mg). After cooling to 0° C., acrylic chloride (2.3 μl) dissolved in chloroform (100 μl) was added thereto, and the mixture was stirred at room temperature for 10 minutes. After halting the reaction using a saturated aqueous sodium bicarbonate solution, the resulting product was extracted with ethyl acetate. After drying the result over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: ethyl acetate/methanol) to obtain the title compound as a white solid (6.5 mg). Table 1 shows the physical properties thereof.

Workup

  1. distillationAfter distilling
  2. customthe solvent of the resulting reaction mixture
  3. distillationoff under reduced pressure, toluene azeotropic distillation

Sources & evidence

ORD record
ord-60d6b52f08a94c26a1a84800037681f2
Source dataset
uspto-grants-2015_08
Patent number
US09108973B2

Reaction notes

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