Acetic Acid → HCID 86732042, compound

HRID 1498783Notes

Reaction equation

HRID 1498783 reaction equation
[CH3:1][C:2]1[N:6]=[C:5]([CH3:7])[N:4]([C:8]2[N:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[N:11]=[C:10]([C@@H:18]3[CH2:20][C@H:19]3[CH:21]=O)[CH:9]=2)[N:3]=1.[CH3:23][NH:24][C:25]1[C:26]([NH2:31])=[CH:27][CH:28]=[CH:29][CH:30]=1.CC(O)=O>C(O)C.[O-]S([O-])(=O)=O.[Cu+2]>[CH3:1][C:2]1[N:6]=[C:5]([CH3:7])[N:4]([C:8]2[N:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[N:11]=[C:10]([C@@H:18]3[CH2:20][C@H:19]3[C:21]3[N:24]([CH3:23])[C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[N:31]=3)[CH:9]=2)[N:3]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 78498N-Methyl-o-phenylenediamineHCID 86732041HCID 86732041, compound

Product 1

HCID 86732042HCID 86732042, compound

Reagents, catalysts & solvents 2

HCID 24462Copper SulfateCatalystHCID 702EthanolSolvent

Procedure

To the mixture of trans-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-(trifluoromethyl)pyrimidin-4-yl)cyclopropanecarbaldehyde (16-6, 280 mg, 0.899 mmol, 1.0 eq.) and N1-methylbenzene-1,2-diamine (0.11 mL, 0.989 mmol, 1.1 eq.) in anhydrous ethanol (5.0 mL) at room temperature was added glacial AcOH (0.062 mL, 1.08 mmol, 1.2 eq.) followed by anhydrous CuSO4 (158 mg, 0.989 mmol, 1.1 eq.). The resulting brownish mixture was stirred at room temperature for 4 hours under an atmosphere of nitrogen gas. The mixture was concentrated in vacuo and neutralized with 7 M NH3 in methanol (1.0 mL). Then it was filtered and concentrated to dryness. The resulting residue was purified by silica gel column chromatography (0-100% ethyl acetate in hexanes) to give trans-2-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-(trifluoromethyl)pyrimidin-4-yl)cyclopropyl)-1-methyl-1H-benzo[d]imidazole (16-7) as a light brown solid. 1H NMR (300 MHz, CDCl3) 8.07 (s, 1H), 7.74-7.66 (m, 1H), 7.35-7.22 (m, 3H), 3.84 (s, 3H), 3.08-2.99 (m, 1H), 2.98-2.88 (m, 1H), 2.93 (s, 3H), 2.42 (s, 3H), 2.13-2.02 (m, 2H). LRMS m/z (M+H) 414 found, 414 required. m.p. 151-153° C.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. filtrationThen it was filtered
  3. concentrationconcentrated to dryness
  4. customThe resulting residue was purified by silica gel column chromatography (0-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-5e56513fc53042938983c621b42aea7b
Source dataset
uspto-grants-2015_12
Patent number
US09200001B2

Reaction notes

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