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

HRID 1498778Notes

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]([S:16][CH3:17])[N:9]=2)[N:3]=1.[N+](=[CH:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[N-]>C1(C)C=CC=CC=1>[CH2:24]([O:23][C:21]([C@@H:20]1[CH2:15][C@H:14]1[C:12]1[CH:13]=[C:8]([N:4]2[C:5]([CH3:7])=[N:6][C:2]([CH3:1])=[N:3]2)[N:9]=[C:10]([S:16][CH3:17])[N:11]=1)=[O:22])[CH3:25]

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of 4-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-(methylthio)-6-vinylpyrimidine (1-3) (5.00 g, 20.0 mmol, 1.0 eq.) in degassed toluene (220 mL) was added ethyl diazoacetate (4.3 mL, 40.0 mmol, 2.0 eq.) and the reaction was heated to 120° C. The reaction was monitored by LC-MS and after 6 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 (10-70% ethyl acetate in hexanes) to afford ethyl-trans-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-(methylthio)pyrimidin-4-yl)cyclopropanecarboxylate (1-4) as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.48 (s, 1H), 4.17 (q, 2H, J=7.1 Hz), 2.88 (s, 3H), 2.61-2.53 (m, 1H), 2.53 (s, 3H), 2.41 (s, 3H), 2.41-2.33 (m, 1H), 1.76-1.62 (m, 2H), 1.28 (t, 3H, J=7.1 Hz). LRMS m/z (M+H) 334 found, 334 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 (10-70% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-c1c2f039437543debc9c059e8bf0dee2
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09200001B2

Reaction notes

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