Acetic Acid → 2-(methylthio)-4-(1-phenyl-1H-pyrazol-5-yl)pyrimidine

HRID 2214776Notes

Reaction equation

HRID 2214776 reaction equation
C[N:2](C)/[CH:3]=[CH:4]/[C:5]([C:7]1[CH:12]=[CH:11][N:10]=[C:9]([S:13][CH3:14])[N:8]=1)=O.[C:16]1([NH:22][NH2:23])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(O)(=O)C>C(O)C>[CH3:14][S:13][C:9]1[N:8]=[C:7]([C:5]2[N:22]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:2]=[CH:3][CH:4]=2)[CH:12]=[CH:11][N:10]=1.[CH3:14][S:13][C:9]1[N:8]=[C:7]([C:5]2[CH:4]=[CH:3][N:22]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:23]=2)[CH:12]=[CH:11][N:10]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 7516PhenylhydrazineHCID 21948442(E)-3-(dimethylamino)-1-(2-(methylthio)pyrimidin-4-yl)prop-2-en-1-one

Product 2

HCID 219485112-(methylthio)-4-(1-phenyl-1H-pyrazol-5-yl)pyrimidineHCID 219485342-(methylthio)-4-(1-phenyl-1H-pyrazol-3-yl)pyrimidine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of (2E)-3-(dimethylamino)-1-[2-(methylthio)pyrimidin-4-yl]prop-2-en-1-one (1-4, 3.60 g, 16.1 mmol, 1 equiv), phenylhydrazine (1.58 mL, 16.1 mmol, 1.00 equiv) and acetic acid (90 uL, 1.6 mmol, 0.10 equiv) in ethanol (100 mL) was heated at reflux for 20 hours. The reaction mixture was concentrated and the residue purified by flash column chromatography (hexanes initially, grading to 40% ethyl acetate in hexanes) to give 2-(methylthio)-4-(1-phenyl-1H-pyrazol-5-yl)pyrimidine (1-5) and 2-(methylthio)-4-(1-phenyl-1H-pyrazol-3-yl)pyrimidine (1-6) as white solids. 1H NMR 1–5 (300 MHz, CDCl3) δ 8.44 (d, 1H, J=5.2 Hz), 7.77 (d, 1H, J=1.8 Hz), 7.50–7.30 (m, 5H), 6.95 (d, 1H, J=1.8 Hz), 6.92 (d, 1H, J=5.2 Hz), 2.08 (s, 3H); 1H NMR 1–6 (300 MHz, CDCl3) δ 8.60 (d, 1H, J=4.9 Hz), 8.02 (d, 1H), J=1.8 Hz), 6.92 (d, 1H, J=4.9 Hz), 7.68 (br d, 2H, j=7.8 Hz), 7.52 (br t, 2H, J=7.5 Hz), 7.37 (m, 1H), 7.23 (d, 1H, J=1.8 Hz), 2.68 (s, 3H).

Workup

  1. temperatureat reflux for 20 hours
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue purified by flash column chromatography (hexanes initially

Sources & evidence

ORD record
ord-e6089eca1d7d4c028b17352e4ead53a4
Source dataset
uspto-grants-2006_09
Patent number
US07109204B2

Reaction notes

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