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

HRID 49886

반응식

HRID 49886 반응식
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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
210 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-6aeff8228d214530ae42f062a991b178
출처 데이터셋
uspto-grants-2004_03
특허 번호
US06710047B2

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