Hydrochloric Acid → 1-(2-Bromopyridin-4-yl)-1-(2-cyclopropylpyridin-4-yl)-4-fluoro-1H-isoindol-3-amine

HRID 1662213노트

반응식

HRID 1662213 반응식
C([Li])(C)(C)C.Br[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([CH:13]2[CH2:15][CH2:14]2)[CH:8]=1.[Br:16][C:17]1[CH:22]=[C:21]([C:23]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[C:32]=2[C:38]#[N:39])=[N:24]S(C(C)(C)C)=O)[CH:20]=[CH:19][N:18]=1.Cl>C1COCC1.CO>[Br:16][C:17]1[CH:22]=[C:21]([C:23]2([C:7]3[CH:12]=[CH:11][N:10]=[C:9]([CH:13]4[CH2:15][CH2:14]4)[CH:8]=3)[C:31]3[C:32](=[C:33]([F:37])[CH:34]=[CH:35][CH:36]=3)[C:38]([NH2:39])=[N:24]2)[CH:20]=[CH:19][N:18]=1

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 457878654-Bromo-2-cyclopropylpyridineHCID 76821597N-((2-bromopyridin-4-yl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamideHCID 178418306HCID 178418306, 화합물

생성물 1

HCID 585794871-(2-Bromopyridin-4-yl)-1-(2-cyclopropylpyridin-4-yl)-4-fluoro-1H-isoindol-3-amine수율 45.3%

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매3회

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온도
-100 °C

실험 절차

Under an atmosphere of argon, tert-butyllithium (1.7 M in pentane) (0.576 mL, 0.98 mmol) was added dropwise to anhydrous tetrahydrofuran (4.00 mL) at −100° C. 4-Bromo-2-cyclopropylpyridine (0.097 g, 0.49 mmol) in anhydrous THF (2.00 mL) was added dropwise to the mixture. The solution was stirred for 2 minutes before dropwise addition of a solution of N-((2-bromopyridin-4-yl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide (0.200 g, 0.49 mmol) in anhydrous THF (2.00 mL). The reaction was stirred at −100° C. for 20 minutes, then the temperature was raised to −78° C. over a period of 10 minutes. The reaction was stirred at −78° C. for another 60 minutes. MeOH (2.0 mL) was added dropwise at −78° C. followed by hydrogen chloride (1.25 M in methanol) (1.176 mL, 1.47 mmol). The cooling bath was removed and the reaction was left to stir at ambient temperature for 60 minutes. The solvents were evaporated and the residue was partitioned between EtOAc and saturated aqueous NaHCO3. The aqueous layer was extracted with EtOAc (×2), the organics were combined, dried (Na2SO4), filtered and evaporated. Purification by silica chromatography using 0 to 5% (3.5 M ammonia in methanol) in dichloromethane gave the title compound (0.094 g, 45%).

후처리

  1. temperaturethe temperature was raised to −78° C. over a period of 10 minutes
  2. stirringThe reaction was stirred at −78° C. for another 60 minutes
  3. customThe cooling bath was removed
  4. waitthe reaction was left
  5. stirringto stir at ambient temperature for 60 minutes
  6. customThe solvents were evaporated
  7. customthe residue was partitioned between EtOAc and saturated aqueous NaHCO3
  8. extractionThe aqueous layer was extracted with EtOAc (×2)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated
  12. customPurification by silica chromatography

출처 및 근거

ORD 기록
ord-1364d301fcab4396b1f9e25e005db769
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08030500B2

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