p-Toluenesulfonic acid → 4-[2-((S)-1-tert-Butoxycarbonyl-piperidin-3-yloxy)-4-fluoro-phenylamino]-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl ester

HRID 240611Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 240611
[CH3:1][O:2][C:3]([C:5]1[S:14][C:8]2[N:9]=[CH:10][N:11]=[C:12](Cl)[C:7]=2[C:6]=1[CH3:15])=[O:4].[NH2:16][C:17]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:18]=1[O:19][C@H:20]1[CH2:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>O1CCOCC1>[CH3:1][O:2][C:3]([C:5]1[S:14][C:8]2[N:9]=[CH:10][N:11]=[C:12]([NH:16][C:17]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:18]=3[O:19][C@H:20]3[CH2:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21]3)[C:7]=2[C:6]=1[CH3:15])=[O:4]

Komponenten

6

Edukt 4

HCID 6101p-Toluenesulfonic acidHCID 516892Sodium BicarbonateHCID 2759834Methyl 4-chloro-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylateHCID 58413089(S)-tert-butyl 3-(2-amino-5-fluorophenoxy)piperidine-1-carboxylate

Produkt 1

HCID 584130264-[2-((S)-1-tert-Butoxycarbonyl-piperidin-3-yloxy)-4-fluoro-phenylamino]-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

4-Chloro-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl ester (1.17 g), (S)-tert-butyl 3-(2-amino-5-fluorophenoxy)piperidine-1-carboxylate (Intermediate 1.1 g) was dissolved in dioxane (10 ml) and p-toluenesulfonic acid (61 mg) was added. The reaction was heated at 70° C. for 1.5 h. The solution was poured into sat. NaHCO3 (50 ml) and extracted with chloroform. The organic phases were passed through a phase separator and concentrated in vaco. The sample was purified by chromatography (silica gel; solvent: isohexan:EtOAc 3:1→2:1) to give the desired product.

Aufarbeitung

  1. extractionextracted with chloroform
  2. concentrationconcentrated in vaco
  3. customThe sample was purified by chromatography (silica gel; solvent: isohexan:EtOAc 3:1→2:1)

Quellen und Nachweise

ORD-Eintrag
ord-7ad2fbc504214d30bb261400b1bdc7c8
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08648068B2

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