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

HRID 516162노트

반응식

HRID 516162 반응식
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

참가 물질

3

반응물 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

생성물 1

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

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-fdd25b3e654c40e1be7a9bb3b992ffea
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108973B2

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