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

HRID 539715

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

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).

Workup

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

Sources & evidence

ORD record: ord-d2596ea1680648daab9a84ecb290a8dc
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08871768B2

Linked notes

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