Diisopropylethylamine → Tert-butyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)piperazine-1-carboxylate

HRID 2093443

Reaktionsgleichung

ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[C:15]([F:34])=[C:16]([CH:31]=[CH:32][CH:33]=1)[CH2:17][N:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1.CCN(C(C)C)C(C)C.[NH2:44][C:45]1[CH:50]=[CH:49][N:48]=[C:47]([CH3:51])[CH:46]=1>C1COCC1.CCOC(C)=O>[F:34][C:15]1[C:14]([NH:13][C:5]([NH:44][C:45]2[CH:50]=[CH:49][N:48]=[C:47]([CH3:51])[CH:46]=2)=[O:11])=[CH:33][CH:32]=[CH:31][C:16]=1[CH2:17][N:18]1[CH2:19][CH2:20][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:22][CH2:23]1

Komponenten

Reaktionsbedingungen

Temperatur: 0 °C

Versuchsvorschrift

To a 0° C. solution of triphosgene (959 mg, 3.24 mmol, 0.35 equiv) in THF (45 mL) was slowly added via cannula a solution of tert-butyl 4-(3-amino-2-fluorobenzyl)piperazine-1-carboxylate (2.86 g, 9.25 mmol, 1.0 equiv) and DIPEA (3.2 mL, 18.5 mmol, 2.0 equiv) in THF (25 mL) over approximately 20 minutes. The solution was stirred for an additional 15 min at 0° C., and 4-amino-2-methylpyridine was then added. After stirring at room temperature for 72 h, the reaction was diluted with EtOAc, washed with aq. satd. NaHCO3 and brine, dried over sodium sulfate, filtered and concentrated in vacuo. Purification by reverse phase preparative HPLC provided tert-butyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)piperazine-1-carboxylate (1.77 g, 43%). LCMS m/z (APCI)=444.3 (M+H).

Aufarbeitung

stirringAfter stirring at room temperature for 72 h
washwashed with aq. satd
dry with materialNaHCO3 and brine, dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by reverse phase preparative HPLC

Quellen und Nachweise

ORD-Eintrag: ord-260b8aeeb79442ad84648682953c03c7
Quelldatensatz: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08445495B2

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