Phosphorus oxide (P4O10) → HCID 42630191, compound

HRID 254322Notes

Reaction equation

HRID 254322 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH:12]=[C:11]([CH3:13])[N:10]=[C:9]2[C:14]2[CH:19]=[CH:18][N:17]=[CH:16][C:15]=2[CH3:20])[C:5]([NH:21][C:22](=O)[CH3:23])=[C:4]([O:25][CH3:26])[CH:3]=1.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.O=P(Cl)(Cl)Cl>CO.ClCCl>[F:1][C:2]1[CH:7]=[C:6]2[C:5]([N:21]=[C:22]([CH3:23])[C:12]3[N:8]2[C:9]([C:14]2[CH:19]=[CH:18][N:17]=[CH:16][C:15]=2[CH3:20])=[N:10][C:11]=3[CH3:13])=[C:4]([O:25][CH3:26])[CH:3]=1

Participants

6

Reactant 3

HCID 14812Phosphorus oxide (P4O10)HCID 24813Phosphorus oxychlorideHCID 57732475HCID 57732475, compound

Product 1

HCID 42630191HCID 42630191, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of intermediate N-(4-fluoro-2-methoxy-6-(4-methyl-2-(3-methylpyridin-4-yl)-1H-imidazol-1-yl)phenyl)acetamide (1.58 g, 4.46 mmol) and P2O5 (3.16 g, 22.3 mmol) was added 60 mL of POCl3 under nitrogen. The resulting mixture was stirred at 120° C. for 6 hours and cooled to room temperature. Majority of solvent was removed under vacuum and the residue was diluted with ethyl acetate. The mixture was transferred very carefully into iced-50% NaOH solution. The mixture was stirred for 10 minutes (make sure pH>7) and extracted with ethyl acetate (3×). Condensation and column purification using 4-8% MeOH in dichloromethane as eluent provided 880 mg (60% yield) of 8-fluoro-6-methoxy-3,4-dimethyl-1-(3-methylpyridin-4-yl)imidazo[1,5-a]quinoxaline as an offwhite powder. 1H NMR (400 MHz, DMSO) δ ppm 8.68 (s, 1H), 8.60 (d, 1H), 7.48 (d, 1H), 7.00 (dd, 1H), 6.16 (dd, 1H), 3.88 (s, 3H), 2.75 (s, 3H), 2.69 (s, 3H), 1.98 (s, 3H). EIMS 337.1 [M+H]+.

Workup

  1. temperaturecooled to room temperature
  2. customMajority of solvent was removed under vacuum
  3. additionthe residue was diluted with ethyl acetate
  4. stirringThe mixture was stirred for 10 minutes (make sure pH>7)
  5. extractionextracted with ethyl acetate (3×)
  6. customCondensation and column purification

Sources & evidence

ORD record
ord-1e82b06a867f47c38fd7847b37833626
Source dataset
uspto-grants-2011_01
Patent number
US07875618B2

Reaction notes

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