Potassium Carbonate → tert-Butyl [4-(2-{3-[(2-chloro-5-fluoropyrimidin-4-yl)amino]phenyl}ethyl)pyridin-2-yl]carbamate

HRID 541855Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 541855
[NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH:11]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:24][C:25]1[N:30]=[C:29](Cl)[C:28]([F:32])=[CH:27][N:26]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:24][C:25]1[N:30]=[C:29]([NH:1][C:2]2[CH:3]=[C:4]([CH2:8][CH2:9][C:10]3[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:20])([CH3:22])[CH3:21])[CH:11]=3)[CH:5]=[CH:6][CH:7]=2)[C:28]([F:32])=[CH:27][N:26]=1

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 57961683Tert-butyl {4-[2-(3-aminophenyl)ethyl]pyridin-2-yl}carbamate

Produkt 1

HCID 57961852tert-Butyl [4-(2-{3-[(2-chloro-5-fluoropyrimidin-4-yl)amino]phenyl}ethyl)pyridin-2-yl]carbamateAusbeute 41,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of tert-butyl {4-[2-(3-aminophenyl)ethyl]pyridin-2-yl}carbamate (160 mg, 0.51 mmol) (prepared in Example C15, step C) and 2,4-dichloro-5-fluoropyrimidine (89.5 mg, 0.54 mmol) in N,N-dimethylformamide (2.3 mL) was added potassium carbonate (212 mg, 1.53 mmol). The resultant mixture was stirred overnight at room temperature. The reaction mixture was filtered first to remove K2CO3, followed by quenching with water. EtOAc was added and the layers were separated. The aqueous layer was extracted with EtOAc twice. The combined organic layers were washed with water and then dried (Na2SO4), filtered and concentrated to give the residue, which was purified by silica gel column chromatography to give the desired product as an off-white solid (93 mg, 41%). LCMS for C22H24ClFN5O2 (M+H)+: m/z=444.1.

Aufarbeitung

  1. filtrationThe reaction mixture was filtered first
  2. customto remove K2CO3
  3. customby quenching with water
  4. additionEtOAc was added
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with EtOAc twice
  7. washThe combined organic layers were washed with water
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give the residue, which
  12. customwas purified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-51731c3d15504966b43b55d75ae621a9
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08871753B2

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