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

HRID 1498804Notes

Reaction equation

HRID 1498804 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]([CH:14]3[CH2:15][CH:19]3[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:13]=2)[N:3]=1

Participants

4

Reactant 2

HCID 12192Ethyl diazoacetateHCID 86732066HCID 86732066, compound

Product 1

HCID 71547209ethyl 2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropanecarboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 4-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methyl-6-vinylpyrimidine (2-3, 500 mg, 2.323 mmol 1.0 eq.) in toluene (35 mL) was heated under nitrogen to 120° C. To the reaction mixture was added ethyl diazoacetate (0.602 mL, 5.81 mmol, 2.5 eq.) dropwise. Upon complete addition, heating was continued for 2 hours. A mix of trans (major) and cis (minor) products were observed. Toluene was removed by roto-evaporation and the resulting residue purified by silica gel column chromatography (0-100% ethyl acetate in hexanes). The major product peak was collected and concentrated to afford ethyl 2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropanecarboxylate (2-4). 1H NMR (500 MHz, CDCl3) δ 7.59 (s, 1H), 4.18 (m, 2H), 2.89 (s, 3H), 2.62 (s, 3H), 2.60 (m, 1H), 2.41 (s, 3H), 2.36 (m, 1H), 1.71 (m, 1H), 1.66 (m, 1H), 1.28 (t, 3H, J=6.4 Hz). LRMS m/z (M+H) 302.3 found, 302.2 required.

Workup

  1. additionUpon complete addition
  2. temperatureheating
  3. additionA mix of trans (major) and cis (minor) products
  4. customToluene was removed by roto-evaporation
  5. customthe resulting residue purified by silica gel column chromatography (0-100% ethyl acetate in hexanes)
  6. customThe major product peak was collected
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-ae3d3b89cc4847e39f3c70491a401026
Source dataset
uspto-grants-2015_12
Patent number
US09200001B2

Reaction notes

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