Phosphorus oxychloride → 5-chloro-1-(2,4-difluorophenyl)-7-ethyl-1H-pyrazolo[4,3-b]pyrazin-6(7H)-one

HRID 383571Notes

Reaction equation

HRID 383571 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]2[N:14]([CH2:20][CH3:21])[C:15](=[O:19])[C:16](=O)[NH:17][C:12]=2[CH:11]=[N:10]1.O=P(Cl)(Cl)[Cl:24].C(N(CC)C(C)C)(C)C>C1(C)C=CC=CC=1>[Cl:24][C:16]1[C:15](=[O:19])[N:14]([CH2:20][CH3:21])[C:13]2[N:9]([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])[N:10]=[CH:11][C:12]=2[N:17]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 67197558HCID 67197558, compound

Product 1

HCID 671973465-chloro-1-(2,4-difluorophenyl)-7-ethyl-1H-pyrazolo[4,3-b]pyrazin-6(7H)-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 1-(2,4-difluorophenyl)-7-ethyl-1H-pyrazolo[3,4-b]pyrazine-5,6(4H,7H)-dione (330 mg, 1.13 mmol) in 5 mL of toluene was treated with POCl3 (0.16 mL, 1.70 mmol) followed by N,N-diisopropylethylamine (0.16 mL, 0.9 mmol). The reaction mixture was heated in an oil bath at 110° C. for 2.5 h. The volatiles were removed on the rotovap and the residue was dissolved in ice cold DCM (20 mL) and washed with NaHCO3 saturated solution, dried over MgSO4, filtered and concentrated affording 5-chloro-1-(2,4-difluorophenyl)-7-ethyl-1H-pyrazolo[4,3-b]pyrazin-6(7H)-one as a brown amorphous solid. The material was used without further purification. MS (ES+): 311.0 (M+H)+.

Workup

  1. customThe volatiles were removed on the rotovap
  2. dissolutionthe residue was dissolved in ice cold DCM (20 mL)
  3. washwashed with NaHCO3 saturated solution
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-0dc5decdd6e94baa975375546ee16783
Source dataset
uspto-grants-2013_02
Patent number
US08367671B2

Reaction notes

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