1-Piperazinecarboxylic acid, ethyl ester → 4-{5-[2-(2,2,6,6-Tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-thiophen-2-yl}-piperazine-1-carboxylic acid ethyl ester

HRID 1434949Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1434949
Br[C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH:14]3[CH2:19][C:18]([CH3:21])([CH3:20])[NH:17][C:16]([CH3:23])([CH3:22])[CH2:15]3)[N:8]=2)=[CH:4][CH:3]=1.CC([O-])(C)C.[Na+].[CH2:30]([O:32][C:33]([N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)=[O:34])[CH3:31]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:30]([O:32][C:33]([N:35]1[CH2:36][CH2:37][N:38]([C:2]2[S:6][C:5]([C:7]3[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH:14]4[CH2:19][C:18]([CH3:21])([CH3:20])[NH:17][C:16]([CH3:23])([CH3:22])[CH2:15]4)[N:8]=3)=[CH:4][CH:3]=2)[CH2:39][CH2:40]1)=[O:34])[CH3:31]

Komponenten

6

Edukt 3

HCID 84311-Piperazinecarboxylic acid, ethyl esterHCID 23676156Sodium t-butoxideHCID 57936128{4-[5-Bromothiophen-2-yl]-pyrimidin-2-yl}-(2,2,6,6-tetramethyl-piperidin-4-yl)-amine

Produkt 1

HCID 113748694-{5-[2-(2,2,6,6-Tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-thiophen-2-yl}-piperazine-1-carboxylic acid ethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

[4-(5-Bromo-thiophen-2-yl)-pyrimidin-2-yl]-(2,2,6,6-tetramethyl-piperidin-4-yl)-amine (Step C of Example 5, 198 mg, 0.5 mmol), NaOtBu (53 mg, 0.55 mmol), R-(+)-BINAP (6.2 mg, 0.01 mmol), Pd(OAc)2 (6.2 mg, 0.027 mol) and N-ethoxycarbonylpiperazine (158 mg, 1.0 mmol) were refluxed in 1,4-dioxan for 18 hours. The reaction mixture was poured on water and extracted three times with EtOAc. The combined organic phases were dried over sodium sulfate, filtered, and purified via chromatography on silicagel (TBME/MeOH/ammonia:98/1.8/0.2 to 95/4.5/0.5) to give the title compound as yellow solid. Yield: 120 mg (50%).

Aufarbeitung

  1. additionThe reaction mixture was poured on water
  2. extractionextracted three times with EtOAc
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. filtrationfiltered
  5. custompurified via chromatography on silicagel (TBME/MeOH/ammonia:98/1.8/0.2 to 95/4.5/0.5)

Quellen und Nachweise

ORD-Eintrag
ord-4103368cd2954852b84ffa0b548fc911
Quelldatensatz
uspto-grants-2009_11
Patentnummer
US07615562B2

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