1,4-Dioxane hydrochloride → (S)-5-((3,5-dimethoxyphenyl)ethynyl)-7-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 516162Notes

Reaction equation

HRID 516162 reaction equation
Cl.O1CCOCC1.[NH2:8][C:9]1[C:10]2[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)=[CH:16][N:15]([C@H:30]3[CH2:34][CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31]3)[C:11]=2[N:12]=[CH:13][N:14]=1>>[CH3:27][O:26][C:24]1[CH:25]=[C:20]([C:19]#[C:18][C:17]2[C:10]3[C:9]([NH2:8])=[N:14][CH:13]=[N:12][C:11]=3[N:15]([C@H:30]3[CH2:34][CH2:33][NH:32][CH2:31]3)[CH:16]=2)[CH:21]=[C:22]([O:28][CH3:29])[CH:23]=1

Participants

3

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 89870927(S)-tert-butyl 3-(4-amino-5-((3,5-dimethoxyphenyl)ethynyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate

Product 1

HCID 89870819(S)-5-((3,5-dimethoxyphenyl)ethynyl)-7-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amineYield 127.5%

Procedure

4N-Hydrochloric acid/1,4-dioxane (2 ml) was added to the (S)-tert-butyl 3-(4-amino-5-((3,5-dimethoxyphenyl)ethynyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (30 mg) obtained in Step 3 above, 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 (S)-5-((3,5-dimethoxyphenyl)ethynyl)-7-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (30 mg). A portion of the resulting crude product (10 mg), 4-(dimethylamino)but-2-enoic acid hydrochloride (5.9 mg), and HATU (14 mg) were dissolved in DMF (1.0 ml). DIPEA (50 μl) was added thereto and stirred at room temperature for 5 minutes. Chloroform and water were added to the reaction mixture to separate the organic layer. After being washed with a saturated sodium chloride solution, the organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by preparative reversed-phase HPLC purification (water/acetonitrile (0.1% formic acid)) to obtain the title compound as a colorless, amorphous substance (3.9 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-fdd25b3e654c40e1be7a9bb3b992ffea
Source dataset
uspto-grants-2015_08
Patent number
US09108973B2

Reaction notes

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