3-Chloro-4-fluoroaniline → 1-(3-Chloro-4-fluoroanilino)-4-(4-pyridylmethyl)phthalazine

HRID 1384124Notes

Reaction equation

HRID 1384124 reaction equation
O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.Cl.C(N(CC)CC)C.[Cl:23][C:24]1[CH:25]=[C:26]([CH:28]=[CH:29][C:30]=1[F:31])[NH2:27].[N:32]1[CH:37]=[CH:36][C:35]([CH2:38][C:39]2[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[C:42](=O)[NH:41][N:40]=2)=[CH:34][CH:33]=1.[OH-].[Na+]>O.ClCCl>[Cl:23][C:24]1[CH:25]=[C:26]([CH:28]=[CH:29][C:30]=1[F:31])[NH:27][C:42]1[C:43]2[C:48](=[CH:47][CH:46]=[CH:45][CH:44]=2)[C:39]([CH2:38][C:35]2[CH:36]=[CH:37][N:32]=[CH:33][CH:34]=2)=[N:40][N:41]=1

Participants

8

Reactant 5

HCID 97083-Chloro-4-fluoroanilineHCID 11130Triethylamine hydrochlorideHCID 14798Sodium HydroxideHCID 14812Phosphorus oxide (P4O10)HCID 7899544-(4-Pyridylmethyl)-1(2H)-phtalazinone

Product 1

HCID 97991931-(3-Chloro-4-fluoroanilino)-4-(4-pyridylmethyl)phthalazine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
200 °C

Procedure

A mixture of 1.42 g (10 mmol) phosphorus pentoxide, 1.38 g (10 mmol) triethylamine hydrochloride, and 1.46 g (10 mmol) 3-chloro-4-fluoroaniline is heated and stirred in a nitrogen atmosphere at 200° C. until a homogeneous melt has formed. To the melt, 0.593 g (2.5 mmol) 4-(4-pyridylmethyl)-1 (2H)-phthalazinone is added and the reaction mixture stirred for a further 3 h at 200° C. After cooling to RT, the hyalinocrystalline reaction mixture is distributed between 150 ml dichloromethane and a mixture of 10 ml water and 20 ml 2N sodium hydroxide solution with intensive stirring and sonication. The organic phase washed with water and dried over sodium sulfate is concentrated by evaporation and the residue recrystallized from acetate. Title compound is obtained after a second recrystallization from methanol/water and drying under HV (8 h at 10° C.); m.p. 185-187° C.; ESI-MS: (M+H)+=365.

Workup

  1. temperatureis heated
  2. customhas formed
  3. stirringthe reaction mixture stirred for a further 3 h at 200° C
  4. temperatureAfter cooling to RT
  5. customthe hyalinocrystalline reaction mixture
  6. stirringwith intensive stirring
  7. customsonication
  8. washThe organic phase washed with water
  9. dry with materialdried over sodium sulfate
  10. concentrationis concentrated by evaporation
  11. customthe residue recrystallized from acetate

Sources & evidence

ORD record
ord-0ea3ea6ff6334b7ebbcfe275528f0573
Source dataset
uspto-grants-2001_07
Patent number
US06258812B1

Reaction notes

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