Cyclopropylacetylene → Tert-butyl 4-(5-(cyclopropylethynyl)pyrimidin-2-yl)piperazine-1-carboxylate

HRID 522659Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[C:21]([CH:23]1[CH2:25][CH2:24]1)#[CH:22]>C(NCC)C.CS(C)=O.C(OCC)(=O)C.[Cu]I>[CH:23]1([C:21]#[C:22][C:2]2[CH:3]=[N:4][C:5]([N:8]3[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]3)=[N:6][CH:7]=2)[CH2:25][CH2:24]1

Participants

Conditions

Temperature: 100 °C

Procedure

In a sealed tube, the mixture of tert-butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate (1.0 g, 2.9 mmol), ethynylcyclopropane (482 mg, 7.3 mmol), tetrakis(triphenyl-phosphine)palladium (335 mg, 0.29 mmol) and copper(I) iodide (28 mg, 0.15 mmol) in diethylamine (10 mL) and dimethyl sulfoxide (10 mL) was stirred at 100° C. for 3 hours under nitrogen atmosphere. The mixture was then diluted with ethyl acetate (100 mL) and washed with water and brine. The organic phase was dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography eluting with petroleum ether:ethyl acetate=15:1 to afford tert-butyl 4-(5-(cyclopropylethynyl)pyrimidin-2-yl)piperazine-1-carboxylate (930 mg, 98%) as a yellow solid. MS (ES+) C18H24N4O2 requires: 328, found: 329 [M+H]+.

Workup

washwashed with water and brine
dry with materialThe organic phase was dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe residue was purified by silica gel chromatography
washeluting with petroleum ether

Sources & evidence

ORD record: ord-29af3252079a40b5b349839a47726078
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09334263B2

Reaction notes

Loading…