Toluene → HCID 178432488, compound

HRID 931335Notes

Reaction equation

HRID 931335 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[C:10]([CH3:14])[N:11]([NH2:13])[CH:12]=1.C(O)(=O)C.[CH:19](N)=[NH:20].C1(C)C=CC=CC=1>CC(O)CC>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[C:10]([CH3:14])[N:11]([NH:13][CH:19]=[NH:20])[CH:12]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 160693Formamidine acetateHCID 1176783184-(2-fluorophenyl)-2-methyl-1H-imidazol-1-amine

Product 1

HCID 178432488HCID 178432488, compound

Reagents, catalysts & solvents 1

HCID 6568(+-)-2-ButanolSolvent

Procedure

Compound C3 (9.95 g, 52.0 mmol) and formamidine acetate (previously azeotroped with toluene, 13.5 g, 130 mmol) were combined in 2-butanol (160 mL) and heated at reflux for 3 hours. The reaction mixture was cooled and concentrated in vacuo. The residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution, and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was suspended in a mixture of heptane and ethyl acetate; filtration provided the product as a pale brown powder. Yield: 8.20 g, 37.6 mmol, 72%. LCMS m/z 219.3 [M+H]+. 1H NMR (500 MHz, DMSO-d6), presumed to be a mixture of rotamers and/or tautomers; characteristic peaks: δ 7.99-8.07 (m, 1.6H), 7.51 and 7.52 (2 s [1:1 ratio], 0.6H), 7.30 (dd, J=9.8, 9.8 Hz, 0.4H), 7.16-7.21 (m, 3.4H), 2.26 and 2.18 (2 s [1.6:1 ratio], 3H).

Workup

  1. temperatureheated
  2. temperatureat reflux for 3 hours
  3. temperatureThe reaction mixture was cooled
  4. concentrationconcentrated in vacuo
  5. customThe residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
  6. extractionthe aqueous layer was extracted twice with ethyl acetate
  7. dry with materialThe combined organic layers were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. additionThe residue was suspended in a mixture of heptane and ethyl acetate
  11. filtrationfiltration

Sources & evidence

ORD record
ord-782530c4847e4fcaaf930fe2b10e95aa
Source dataset
uspto-grants-2016_03
Patent number
US09296761B2

Reaction notes

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