Ammonia → 3-[1-(2,3-Difluorobenzyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-7,7-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-e][1,2,4]triazin-6-one

HRID 570553Notes

Reaction equation

HRID 570553 reaction equation
[F:1][C:2]1[C:32]([F:33])=[CH:31][CH:30]=[CH:29][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([CH3:14])=[N:12][CH:13]=[C:8]2[C:7]([C:15]2[N:16]=[N:17][C:18]([C:22]([CH3:28])([CH3:27])[C:23]([O:25]C)=O)=[C:19](O)[N:20]=2)=[N:6]1.P(Cl)(Cl)(Cl)=O.[NH3:39]>C(#N)C>[F:1][C:2]1[C:32]([F:33])=[CH:31][CH:30]=[CH:29][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([CH3:14])=[N:12][CH:13]=[C:8]2[C:7]([C:15]2[N:16]=[N:17][C:18]3[C:22]([CH3:28])([CH3:27])[C:23](=[O:25])[NH:39][C:19]=3[N:20]=2)=[N:6]1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 24813Phosphorus oxychlorideHCID 178500130HCID 178500130, compound

Product 1

HCID 716126543-[1-(2,3-Difluorobenzyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-7,7-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-e][1,2,4]triazin-6-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

160 mg (purity 89%, 0.313 mmol) of methyl 2-{3-[1-(2,3-difluorobenzyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-5-hydroxy-1,2,4-triazin-6-yl}-2-methylpropanoate were admixed with 4 ml (42.913 mmol) of phosphoryl chloride and the mixture was stirred at RT for 2.5 h. The reaction solution was diluted with 20 ml of dry acetonitrile and gradually added dropwise while cooling with ice to 40 ml of a 25% aqueous ammonia solution, and the mixture was stirred at RT for 1 h. The reaction mixture was concentrated on a rotary evaporator and the precipitate was filtered off. The residue was stirred with hot ethanol/water and filtered with suction, and the solids were dried under high vacuum. 70 mg of the target compound were obtained (52% of theory).

Workup

  1. additiongradually added dropwise
  2. stirringthe mixture was stirred at RT for 1 h
  3. concentrationThe reaction mixture was concentrated on a rotary evaporator
  4. filtrationthe precipitate was filtered off
  5. stirringThe residue was stirred with hot ethanol/water
  6. filtrationfiltered with suction
  7. customthe solids were dried under high vacuum

Sources & evidence

ORD record
ord-134bdedcf5c34315b94eacf3c832481c
Source dataset
uspto-grants-2015_05
Patent number
US09023849B2

Reaction notes

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