Ammonia → 1-(3-Methylanilino)-4-(4-pyridylmethyl)phthalazine

HRID 1384125Notes

Reaction equation

HRID 1384125 reaction equation
O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.Cl.C(N(CC)CC)C.[NH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[CH:25]=1.[N:31]1[CH:36]=[CH:35][C:34]([CH2:37][C:38]2[C:47]3[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=3)[C:41](=O)[NH:40][N:39]=2)=[CH:33][CH:32]=1.CN(C)C(=O)N(C)C.N>O.ClCCl>[CH3:30][C:26]1[CH:25]=[C:24]([CH:29]=[CH:28][CH:27]=1)[NH:23][C:41]1[C:42]2[C:47](=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:38]([CH2:37][C:34]2[CH:35]=[CH:36][N:31]=[CH:32][CH:33]=2)=[N:39][N:40]=1

Participants

9

Reactant 6

HCID 222AmmoniaHCID 7934m-ToluidineHCID 11130Triethylamine hydrochlorideHCID 12437TetramethylureaHCID 14812Phosphorus oxide (P4O10)HCID 7899544-(4-Pyridylmethyl)-1(2H)-phtalazinone

Product 1

HCID 64193871-(3-Methylanilino)-4-(4-pyridylmethyl)phthalazine

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
200 °C

Procedure

A mixture of 2.39 g (16.8 mmol) phosphorus pentoxide, 2.31 g (16.8 mmol) triethylamine hydrochloride, and 1.82 ml (16.8 mmol) m-toluidine is heated and stirred in a nitrogen atmosphere at 200° C. until a homogeneous melt has formed. To the melt, 1 g (4.2 mmol) 4-(4-pyridylmethyl)-1(2H)-phthalazinone is added and the reaction mixture stirred for a further 3.5 h at 205° C. After cooling to about 170° C., 4 ml tetramethylurea is added to the reaction mixture, followed by 2 ml water at about 110° C. The mixture is stirred for a further 30 min while cooling to RT and then distributed between dichloromethane and a mixture of 20 ml water and 5 ml conc. ammonia. The organic phase dried over sodium sulfate is concentrated by evaporation and the residue purified on silica gel by flash chromatography using acetate and acetate/methanol (99:1 and 19:1). Title compound is obtained after crystallization of the product-containing fractions from acetonitrile and subsequent recrystallzation from acetate; m.p. 141-143° C.; ESI-MS: (M+H)+=327.

Workup

  1. temperatureis heated
  2. customhas formed
  3. stirringthe reaction mixture stirred for a further 3.5 h at 205° C
  4. temperatureAfter cooling to about 170° C.
  5. stirringThe mixture is stirred for a further 30 min
  6. temperaturewhile cooling to RT
  7. dry with materialThe organic phase dried over sodium sulfate
  8. concentrationis concentrated by evaporation
  9. customthe residue purified on silica gel by flash chromatography

Sources & evidence

ORD record
ord-f0baa43284564c4ea0760b4bb0739141
Source dataset
uspto-grants-2001_07
Patent number
US06258812B1

Reaction notes

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