Ethyl diazoacetate → ethyl trans-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropanecarboxylate

HRID 1498815Notes

Reaction equation

[CH3:1][C:2]1[N:6]=[C:5]([CH3:7])[N:4]([C:8]2[CH:13]=[C:12]([CH:14]=[CH2:15])[N:11]=[C:10]([CH3:16])[N:9]=2)[N:3]=1.[N+](=[CH:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])=[N-]>C1(C)C=CC=CC=1>[CH3:1][C:2]1[N:6]=[C:5]([CH3:7])[N:4]([C:8]2[N:9]=[C:10]([CH3:16])[N:11]=[C:12]([C@@H:14]3[CH2:15][C@H:19]3[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:13]=2)[N:3]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of 4-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methyl-6-vinylpyrimidine (1-3) (1.00 g, 4.65 mmol, 1.0 eq.) in degassed toluene (20 mL) was added ethyl diazoacetate (0.98 mL, 9.30 mmol, 2.0 eq.) and the reaction was heated to 120° C. The reaction was monitored by LC-MS and after 2 hours the mixture was cooled to room temperature and the toluene was removed by roto-evaporation. The resulting residue was purified by silica gel column chromatography (10-40% ethyl acetate in hexanes) to afford ethyl trans-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropanecarboxylate (2-1) as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.58 (s, 1H), 4.17 (q, 2H, J=7.1 Hz), 2.88 (s, 3H), 2.64-2.55 (m, 1H), 2.62 (s, 3H), 2.41 (s, 3H), 2.36 (ddd, 1H, J=8.6, 5.7, 3.8 Hz), 1.74-1.61 (m, 2H), 1.28 (t, 3H, J=7.1 Hz). LRMS m/z (M+H+) 302 found, 302 required.

Workup

temperaturethe mixture was cooled to room temperature
customthe toluene was removed by roto-evaporation
customThe resulting residue was purified by silica gel column chromatography (10-40% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-eef2015a79584b2da0425726a6a303d7
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09200001B2

Reaction notes

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