Diisopropylethylamine → Ethyl 2-(4-tert-butoxycarbonylpiperazin-1-yl)-5-methylamino-thiazole-4-carboxylate

HRID 1775354Notes

Reaction equation

Br[C:2]1[S:3][C:4]([NH:12][CH3:13])=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1.[N:14]1([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.CCN(C(C)C)C(C)C>O1CCOCC1>[C:23]([O:22][C:20]([N:14]1[CH2:19][CH2:18][N:17]([C:2]2[S:3][C:4]([NH:12][CH3:13])=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=2)[CH2:16][CH2:15]1)=[O:21])([CH3:26])([CH3:24])[CH3:25]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of ethyl 2-bromo-5-methylamino-thiazole-4-carboxylate (401 mg, 1.512 mmol) and tert-butyl piperazine-1-carboxylate (1.06 g, 5.69 mmol) in anhydrous dioxane (15 ml) was added DIPEA (2 ml, 11.5 mmol) and the reaction was heated at 100° C. in a sealed flask for 23 hours. The mixture was cooled to room temperature, partitioned between DCM and sat. sodium bicarbonate solution and the phases were separated. The aqueous layer was extracted twice with DCM and the combined organic layers were dried (sodium sulfate) and concentrated under reduced pressure. The residue was purified by column chromatography (silica, gradient from 10 to 70% ethyl acetate in n-heptane) to yield 197 mg of a white solid (0.532 mmol, yield 35%) MS (multi-mode) m/z=371.2 [M+1]+.

Workup

temperatureThe mixture was cooled to room temperature
custompartitioned between DCM and sat. sodium bicarbonate solution
customthe phases were separated
extractionThe aqueous layer was extracted twice with DCM
dry with materialthe combined organic layers were dried (sodium sulfate)
concentrationconcentrated under reduced pressure
customThe residue was purified by column chromatography (silica, gradient from 10 to 70% ethyl acetate in n-heptane)

Sources & evidence

ORD record: ord-17f9f95bb6a346e9a3b2526fc373f2b1
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260441B2

Reaction notes

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