Water → tert-butyl (2S)-2-[({4-[(1-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)amino]quinazolin-7-yl}oxy)methyl]pyrrolidine-1-carboxylate

HRID 639998Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 639998
[F:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:28])[CH2:10][N:11]2[CH:15]=[C:14]([NH:16][C:17]3[C:26]4[C:21](=[CH:22][C:23]([OH:27])=[CH:24][CH:25]=4)[N:20]=[CH:19][N:18]=3)[CH:13]=[N:12]2)[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[CH2:40][C@@H:41]1[CH2:45][CH2:44][CH2:43][N:42]1[C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])(=O)=O.O>CC(N(C)C)=O>[F:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:28])[CH2:10][N:11]2[CH:15]=[C:14]([NH:16][C:17]3[C:26]4[C:21](=[CH:22][C:23]([O:27][CH2:40][C@@H:41]5[CH2:45][CH2:44][CH2:43][N:42]5[C:46]([O:48][C:49]([CH3:50])([CH3:52])[CH3:51])=[O:47])=[CH:24][CH:25]=4)[N:20]=[CH:19][N:18]=3)[CH:13]=[N:12]2)[CH:5]=[CH:6][CH:7]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 10796Cesium carbonateHCID 10039261tert-butyl (2S)-2-[(methanesulfonyloxy)methyl]pyrrolidine-1-carboxylateHCID 136383490N-(3-fluorophenyl)-2-{4-[(7-hydroxyquinazolin-4-yl)amino]-1H-pyrazol-1-yl}acetamide

Produkt 1

HCID 86609383tert-butyl (2S)-2-[({4-[(1-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)amino]quinazolin-7-yl}oxy)methyl]pyrrolidine-1-carboxylateAusbeute 61 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

A solution of N-(3-fluorophenyl)-2-{4-[(7-hydroxyquinazolin-4-yl)amino]-1H-pyrazol-1-yl}acetamide (0.590 g, 0.97 mmol), cesium carbonate (1.95 g, 5.98 mmol) and tert-butyl (2S)-2-{[(methylsulphonyl)oxy]methyl}pyrrolidine-1-carboxylate (0.325 g, 1.16 mmol) in dimethylacetamide (10 ml) was heated at 80° C. for 18 hours. The mixture was poured into water and extracted with ethyl acetate. The organic layer was separated, dried over magnesium sulphate and evaporated in vacuo to leave a brown oil which was purified by silica gel chromatography. Elution with 5 to 7% methanol in dichloromethane gave tert-butyl (2S)-2-[({4-[(1-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)amino]quinazolin-7-yl}oxy)methyl]pyrrolidine-1-carboxylate (0.332 g, 61% yield) as a light brown solid.

Aufarbeitung

  1. extractionextracted with ethyl acetate
  2. customThe organic layer was separated
  3. dry with materialdried over magnesium sulphate
  4. customevaporated in vacuo
  5. customto leave a brown oil which
  6. customwas purified by silica gel chromatography
  7. washElution with 5 to 7% methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-0e0719f077094bb39fecd12e3333e1f4
Quelldatensatz
uspto-grants-2010_04
Patentnummer
US07691867B2

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