Sodium Hydroxide → HCID 78322881, 화합물

HRID 336169

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HRID 336169 반응식
B1(B2C3CCCC2CCC3)C2CCCC1CCC2.[NH2:19][C:20]1[C:21]2[C:28]([C:29]3[CH:30]=[N:31][C:32]4[C:37]([CH:38]=3)=[CH:36][CH:35]=[CH:34][CH:33]=4)=[C:27](Br)[N:26]([CH2:40][C@@H:41]([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])[CH:42]=[CH2:43])[C:22]=2[N:23]=[CH:24][N:25]=1.[OH-].[Na+]>COCCOC>[NH2:19][C:20]1[C:21]2[C:28]([C:29]3[CH:30]=[N:31][C:32]4[C:37]([CH:38]=3)=[CH:36][CH:35]=[CH:34][CH:33]=4)=[C:27]3[N:26]([C:22]=2[N:23]=[CH:24][N:25]=1)[CH2:40][C@@H:41]([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])[CH2:42][CH2:43]3

참가 물질

5

반응물 3

HCID 14798Sodium HydroxideHCID 113224419-Borabicyclo[3.3.1]nonane dimerHCID 86711295HCID 86711295, 화합물

생성물 1

HCID 78322881HCID 78322881, 화합물수율 75%

시약·촉매·용매 1

HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
48 °C

실험 절차

9-Borabicyclo[3.3.1]nonane dimer (431 mg) was added to a solution of (S)-tert-butyl (1-(4-amino-6-bromo-5-(quinolin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)but-3-en-2-yl)carbamate (300 mg) obtained in Reference Example 1 in 1,2-dimethoxyethane (4.5 ml) under a nitrogen atmosphere at room temperature, and the mixture was stirred at 48° C. for 40 minutes. After the mixture was allowed to cool to room temperature, a 4 N sodium hydroxide aqueous solution (2.1 ml) was slowly added to the reaction mixture at room temperature, and degassed under reduced pressure. Under a nitrogen atmosphere, (tetrakistriphenylphosphine)palladium(0) (136 mg) was added thereto, and stirred at 79° C. for 5 hours. After the reaction mixture was cooled, and diluted with ethyl acetate, a saturated ammonium chloride aqueous solution was added. The insoluble matter resulting in this stage was removed by filtration, and the organic layer was separated. The resulting organic layer was dried over anhydrous sodium sulfate and filtered, and then concentrated under reduced pressure to obtain a crude product. The crude product was purified by silica gel column chromatography (developing solvent: ethyl acetate/methanol) to obtain (S)-tert-butyl (4-amino-5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizin-8-yl)carbamate (0.190 g) (yield: 75%) as a light-yellow solid.

후처리

  1. temperatureto cool to room temperature
  2. customdegassed under reduced pressure
  3. additionUnder a nitrogen atmosphere, (tetrakistriphenylphosphine)palladium(0) (136 mg) was added
  4. stirringstirred at 79° C. for 5 hours
  5. temperatureAfter the reaction mixture was cooled
  6. additiondiluted with ethyl acetate
  7. additiona saturated ammonium chloride aqueous solution was added
  8. customThe insoluble matter resulting in this stage
  9. customwas removed by filtration
  10. customthe organic layer was separated
  11. dry with materialThe resulting organic layer was dried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customto obtain a crude product
  15. customThe crude product was purified by silica gel column chromatography (developing solvent: ethyl acetate/methanol)

출처 및 근거

ORD 기록
ord-77b680d9dc5b477894f57b3d777cb059
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08889666B2

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