Ammonia → 3-[1-(2-Fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl]-7,7-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-e][1,2,4]triazin-6-one

HRID 570548Notes

Reaction equation

HRID 570548 reaction equation
[F:1][C:2]1[CH:30]=[CH:29][CH:28]=[CH:27][C:3]=1[CH2:4][N:5]1[C:9]2[CH2:10][CH2:11][CH2:12][C:8]=2[C:7]([C:13]2[N:14]=[N:15][C:16]([C:20]([CH3:26])([CH3:25])[C:21]([O:23]C)=O)=[C:17](O)[N:18]=2)=[N:6]1.P(Cl)(Cl)(Cl)=O.[NH3:36]>C(#N)C>[F:1][C:2]1[CH:30]=[CH:29][CH:28]=[CH:27][C:3]=1[CH2:4][N:5]1[C:9]2[CH2:10][CH2:11][CH2:12][C:8]=2[C:7]([C:13]2[N:14]=[N:15][C:16]3[C:20]([CH3:26])([CH3:25])[C:21](=[O:23])[NH:36][C:17]=3[N:18]=2)=[N:6]1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 24813Phosphorus oxychlorideHCID 178500124HCID 178500124, compound

Product 1

HCID 717466343-[1-(2-Fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-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

48 mg (0.06 mmol, purity 54%) of methyl 2-{3-[1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl]-5-hydroxy-1,2,4-triazin-6-yl}-2-methylpropanoate were admixed with 0.5 ml (5.36 mmol) of phosphoryl chloride and the mixture was stirred at RT for 2.5 h. The reaction solution was diluted with 10 ml of dry acetonitrile and gradually added dropwise while cooling with ice to 5 ml of a 25% aqueous ammonia solution, and the mixture was stirred at RT for 8 h. The reaction mixture was concentrated on a rotary evaporator and the residue was partitioned between dichloromethane/water. The organic phase was dried over sodium sulphate and concentrated on a rotary evaporator. The residue was purified by means of preparative HPLC (eluent: acetonitrile/water with 0.1% hydrochloric acid, gradient 20:80→100:0). 4.5 mg of the target compound were obtained (18% of theory).

Workup

  1. additiongradually added dropwise
  2. stirringthe mixture was stirred at RT for 8 h
  3. concentrationThe reaction mixture was concentrated on a rotary evaporator
  4. customthe residue was partitioned between dichloromethane/water
  5. dry with materialThe organic phase was dried over sodium sulphate
  6. concentrationconcentrated on a rotary evaporator
  7. customThe residue was purified by means of preparative HPLC (eluent: acetonitrile/water with 0.1% hydrochloric acid, gradient 20:80→100:0)

Sources & evidence

ORD record
ord-efeb560fdb3a4497b9ded67f37ef892e
Source dataset
uspto-grants-2015_05
Patent number
US09023849B2

Reaction notes

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