Imidazole → ethyl N-(2-chloro-5-nitropyrimidin-4-yl)-N-phenylalaninate

HRID 530109Notes

Reaction equation

[C:1]1([NH:7][C@H:8]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:15][C:16]1[N:21]=[C:20](Cl)[C:19]([N+:23]([O-:25])=[O:24])=[CH:18][N:17]=1.N1C=CN=C1>ClCCl>[Cl:15][C:16]1[N:21]=[C:20]([N:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C@H:8]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH3:9])[C:19]([N+:23]([O-:25])=[O:24])=[CH:18][N:17]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of ethyl N-phenylalaninate (9.65 g, 50 mmol) and 2,4-dichloro-5-nitropyrimidine (9.7 g, 50 mmol) in anhydrous dichloromethane (100 mL) was stirred for 5 minutes at rt under nitrogen. The solution was then cooled to 0° C. (Ice bath) followed by addition of imidazole (3.41 g, 50 mmol). The resulting reaction mixture was allowed to warm up to rt in 30 min and further heated at 50° C. for 2 h. The reaction was then cooled to rt, washed with water, dried over sodium sulfate and evaporated to give a crude residue, which was purified by silica gel flash chromatography (eluent: ethyl acetate-hexane mixture (5:95)) to afford desired product (22%). 1HNMR (300 MHz, CDCl3): δ 1.29 (t, J=7.2 Hz, 3H), 1.63 (d, J=7.5 Hz, 3H), 4.18-4.27 (m, 2H), 4.90 (q, J=7.2 Hz, 1H), 7.19 (d, J=6.9 Hz, 2H), 7.26-7.39 (m, 3H) and 8.52 (s, 1H).

Workup

customThe resulting reaction mixture
temperatureto warm up to rt in 30 min
temperaturefurther heated at 50° C. for 2 h
temperatureThe reaction was then cooled to rt
washwashed with water
dry with materialdried over sodium sulfate
customevaporated
customto give a crude residue, which
customwas purified by silica gel flash chromatography (eluent: ethyl acetate-hexane mixture (5:95))

Sources & evidence

ORD record: ord-28c3c7c673884169aee1b020beff761e
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09351974B2

Reaction notes

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