Hydrochloric Acid → 1-(3-Bromo-4-fluorophenyl)-4-fluoro-1-(pyrimidin-5-yl)-1H-isoindol-3-amine

HRID 1662179Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1662179
C([Li])CCC.Br[C:7]1[CH:8]=[N:9][CH:10]=[N:11][CH:12]=1.[Br:13][C:14]1[CH:15]=[C:16]([C:21]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[C:30]=2[C:36]#[N:37])=[N:22]S(C(C)(C)C)=O)[CH:17]=[CH:18][C:19]=1[F:20].Cl>C1COCC1>[Br:13][C:14]1[CH:15]=[C:16]([C:21]2([C:7]3[CH:8]=[N:9][CH:10]=[N:11][CH:12]=3)[C:29]3[C:30](=[C:31]([F:35])[CH:32]=[CH:33][CH:34]=3)[C:36]([NH2:37])=[N:22]2)[CH:17]=[CH:18][C:19]=1[F:20]

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 783445-BromopyrimidineHCID 76821603N-((3-Bromo-4-fluorophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamideHCID 178418339Butyllithium

Produkt 1

HCID 585795331-(3-Bromo-4-fluorophenyl)-4-fluoro-1-(pyrimidin-5-yl)-1H-isoindol-3-amineAusbeute 56,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

n-Butyllithium (0.136 mL, 0.34 mmol) was slowly added to 5-bromopyrimidine (50 mg, 0.31 mmol) in THF (1.0 mL) at −78° C. under argon atmosphere. The reaction mixture was stirred for 45 min. N-((3-Bromo-4-fluorophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide (111 mg, 0.26 mmol) in THF (1.0 mL) was added dropwise and the resulting reaction mixture was stirred at −78° C. for 1 h, and then allowed to reach room temperature. The reaction was quenched with water and extracted with ethyl acetate (×3). The combined organic layers were washed with brine and concentrated in vacuo. The residue was dissolved in methanol (2.0 mL) and hydrochloric acid (2.0 M in diethyl ether, 0.393 mL, 0.79 mmol) was added at room temperature. The mixture was stirred over night, and then concentrated in vacuo. The residue was partitioned between aqueous sodium bicarbonate (saturated) and ethyl acetate (×3). The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. Purification by silica gel chromatography using a gradient of 0 to 10% (3.5 M ammonia in methanol) in dichloromethane gave the title compound (59.4 mg, 56% yield). MS (ES+) m/z 401, 403 [M+1]+.

Aufarbeitung

  1. customthe resulting reaction mixture
  2. stirringwas stirred at −78° C. for 1 h
  3. customto reach room temperature
  4. customThe reaction was quenched with water
  5. extractionextracted with ethyl acetate (×3)
  6. washThe combined organic layers were washed with brine
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in methanol (2.0 mL)
  9. stirringThe mixture was stirred over night
  10. concentrationconcentrated in vacuo
  11. customThe residue was partitioned between aqueous sodium bicarbonate (saturated) and ethyl acetate (×3)
  12. dry with materialThe combined organic layers were dried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customPurification by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-77b773ff41a94dd69c6813d883ce79f3
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08030500B2

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