Triethylamine → (2R,4S)-N-[1-(3,5-Bis-trifluoromethyl-benzoyl)-2-benzyl-piperidin-4-yl]-quinoline-4-carboxamide

HRID 1738912노트

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HRID 1738912 반응식
O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.[CH2:16]([C@@H:23]1[CH2:28][C@@H:27]([NH2:29])[CH2:26][CH2:25][N:24]1[C:30](=[O:45])[C:31]1[CH:36]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:34]=[C:33]([C:41]([F:44])([F:43])[F:42])[CH:32]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[N:46]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[C:49]([C:56](O)=[O:57])=[CH:48][CH:47]=1.C(N(CC)CC)C>C(Cl)Cl>[F:43][C:41]([F:44])([F:42])[C:33]1[CH:32]=[C:31]([CH:36]=[C:35]([C:37]([F:38])([F:39])[F:40])[CH:34]=1)[C:30]([N:24]1[CH2:25][CH2:26][C@H:27]([NH:29][C:56]([C:49]2[C:50]3[C:55](=[CH:54][CH:53]=[CH:52][CH:51]=3)[N:46]=[CH:47][CH:48]=2)=[O:57])[CH2:28][C@H:23]1[CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)=[O:45]

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 102434-Quinolinecarboxylic acidHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 22869971(2R,4S)-2-benzyl-1-(3,5-bis-(trifluoromethyl)benzoyl)-4-piperidinamine

생성물 1

HCID 18392944(2R,4S)-N-[1-(3,5-Bis-trifluoromethyl-benzoyl)-2-benzyl-piperidin-4-yl]-quinoline-4-carboxamide

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

2.95 g (11.6 mmol) of bis(2-oxo-3-oxazolidinyl)phosphinic acid chloride are added at 0° C. to a solution of 4.16 g (9.67 mmol) of (2R,4S)-2-benzyl-1-(3,5-bis-trifluoromethyl-benzoyl)-4-piperidineamine [EP 532 456 A1, Example 38 f], 1.84 g (10.6 mmol) of quinoline4-carboxylic acid and 3 ml (21.3 mmol) of triethylamine in 30 ml of methylene chloride and the ice bath is removed after 10 minutes. The reaction mixture is stirred for 4 hours at room temperature and then diluted with methylene chloride. The organic phase is extracted with aqueous 10% citric acid and with 1 N potassium carbonate solution, washed with brine, dried over magnesium sulfate and concentrated to dryness by evaporation. The crude product is chromatographed on silica gel with methylene chloride/acetone (7:3). The title compound is crystallised from methylene chloride/ether/hexane in the form of white crystals. M.p.: 187° C.; TLC: methylene chloride/acetone (7:3) Rf =0.48, FD-MS: M+ =585; [alpha]D=+9.9 (c=1, methylene chloride); analysis: calc.: C=63.59%, H=4.30%, N=7.18%, F=19.47%, found: C=63.50%, H=4.40%, N=7.16%, F=19.45%. ##STR15##

후처리

  1. customthe ice bath is removed after 10 minutes
  2. additiondiluted with methylene chloride
  3. extractionThe organic phase is extracted with aqueous 10% citric acid and with 1 N potassium carbonate solution
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated to dryness by evaporation
  7. customThe crude product is chromatographed on silica gel with methylene chloride/acetone (7:3)
  8. customThe title compound is crystallised from methylene chloride/ether/hexane in the form of white crystals

출처 및 근거

ORD 기록
ord-5f96a656d2334b08bcdb6e955222cc0f
출처 데이터셋
uspto-grants-1999_10
특허 번호
US05965562

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