Triethylamine hydrochloride → 1-(4-tert-Butylanilino)-4-(4-pyridylmethyl)phthalazine dihydrochloride

HRID 49886

Reaction equation

HRID 49886 reaction equation
O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[ClH:15].C(N(CC)CC)C.[C:23]([C:27]1[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][CH:28]=1)([CH3:26])([CH3:25])[CH3:24].[N:34]1[CH:39]=[CH:38][C:37]([CH2:40][C:41]2[C:50]3[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=3)[C:44](=O)[NH:43][N:42]=2)=[CH:36][CH:35]=1>ClCCl>[ClH:15].[ClH:15].[C:23]([C:27]1[CH:28]=[CH:29][C:30]([NH:31][C:44]2[C:45]3[C:50](=[CH:49][CH:48]=[CH:47][CH:46]=3)[C:41]([CH2:40][C:37]3[CH:38]=[CH:39][N:34]=[CH:35][CH:36]=3)=[N:42][N:43]=2)=[CH:32][CH:33]=1)([CH3:26])([CH3:24])[CH3:25]

Participants

6

Reactant 4

HCID 11130Triethylamine hydrochlorideHCID 14812Phosphorus oxide (P4O10)HCID 698614-Tert-ButylanilineHCID 7899544-(4-Pyridylmethyl)-1(2H)-phtalazinone

Product 1

HCID 227420221-(4-tert-Butylanilino)-4-(4-pyridylmethyl)phthalazine dihydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
210 °C

Procedure

In the manner described in Example 45, a mixture of 1.80 g (12.68 mmol) phosphorus pentoxide, 1.73 g (12.6 mmol) triethylamine hydrochloride, 1.9 ml (12.5 mmol) 4-tert-butylaniline, and 1 g (4.2 mmol) 4-(4-pyridylmethyl)-1(2H)-phthalazinone is stirred for 4.5 h at 210° C. The frozen melt is then dissolved in dichloromethane using an ultrasonic bath, filtered off from undissolved components, and the filtrate evaporated in the RE. The oil-like residue is distributed between dichloromethane and a mixture of 20 ml water and 5 ml conc. ammonia, and the organic phase dried over anhydrous sodium sulfate, filtered and evaporated under vacuum. The residue is then stirred with 10 ml acetonitrile, filtered off from some non-transformed 4-(4-pyridylmethyl)-1(2H)-phthalazinone, and the filtrate evaporated under vacuum. Flash chromatography of the residue on silica gel with a particle size of 0.04-0.06 mm using a toluene/acetone mixture (7:3) yields a resin (free base of the title compound), which is dissolved in a mixture of 4 ml methanol and 1.5 ml of 3 N methanolic HCl. After evaporation under vacuum, recrystallization of the residue from methanol/ether, drying under HV (6 h, 80° C.), and equilibration for 16 h at 200° C. and in room atmosphere, title compound is obtained with a water content of 4.47%; m.p. 196-200° C.; ESI-MS: (M+H)+=369.

Workup

  1. filtrationfiltered off from undissolved components
  2. customthe filtrate evaporated in the RE
  3. additiona mixture of 20 ml water and 5 ml conc. ammonia
  4. dry with materialthe organic phase dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customevaporated under vacuum
  7. stirringThe residue is then stirred with 10 ml acetonitrile
  8. filtrationfiltered off from some non-transformed 4-(4-pyridylmethyl)-1(2H)-phthalazinone
  9. customthe filtrate evaporated under vacuum

Sources & evidence

ORD record
ord-6aeff8228d214530ae42f062a991b178
Source dataset
uspto-grants-2004_03
Patent number
US06710047B2

Linked notes

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