Dimethylformamide → 8-Chloro-1-(4-phenoxy-phenyl)-imidazo[1,5-a]pyrazine

HRID 449037Notes

Reaction equation

HRID 449037 reaction equation
[Cl:1][C:2]1[C:3]([CH:8]([C:12]2[CH:17]=[CH:16][C:15]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:14][CH:13]=2)[NH:9][CH:10]=O)=[N:4][CH:5]=[CH:6][N:7]=1.C(N)=O.CN(C=O)C.O=P(Cl)(Cl)Cl.CCOC(C)=O.C(Cl)Cl>CC#N>[Cl:1][C:2]1[C:3]2[N:4]([CH:10]=[N:9][C:8]=2[C:12]2[CH:17]=[CH:16][C:15]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:14][CH:13]=2)[CH:5]=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 21226138Dichloromethane ethylacetateHCID 86636035formamide N-[(3-chloro-pyrazin-2-yl)-(4-phenoxy-phenyl)-methyl]-formamide

Product 1

HCID 866360348-Chloro-1-(4-phenoxy-phenyl)-imidazo[1,5-a]pyrazineYield 92.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of formamide N-[(3-chloro-pyrazin-2-yl)-(4-phenoxy-phenyl)-methyl]-formamide (1.85 g, 5.45 mmol) in CH3CN (50 mL) at 0° C. was added DMF (0.4 mL) and POCl3 (1.52 mL, 16.3 mmol). The mixture was allowed to warm to rt over 16 h. TLC (EtOAc/CH2Cl2, 1:1) showed no starting material. Reaction mixture was evaporated to remove solvents. To the residue was added aq. satd. NaHCO3 (100 mL) and extracted with EtOAc (3×50 mL). Organic layer was washed with water (30 mL) and dried (Na2SO4). Evaporation of solvent gave titled compound (1.62 g, 92%). 1H NMR (CDCl3, 300 MHz) δ 7.13-7.21 (m, 5H), 7.29-7.31 (m, 3H), 7.60-7.64 (m, 2H), 7.68 (d, J=2.4 Hz, 1H), 8.30 (s, 1H).

Workup

  1. customReaction mixture
  2. customwas evaporated
  3. customto remove solvents
  4. additionTo the residue was added aq. satd
  5. extractionNaHCO3 (100 mL) and extracted with EtOAc (3×50 mL)
  6. washOrganic layer was washed with water (30 mL)
  7. dry with materialdried (Na2SO4)
  8. customEvaporation of solvent

Sources & evidence

ORD record
ord-7faf1dfe19964499b833aafa36465a19
Source dataset
uspto-grants-2013_07
Patent number
US08481733B2

Reaction notes

Loading…