Triethylamine → (S)-1-((10-chloro-6,7-dihydro-4-oxo-3-phenyl-4H-benzo(a)quinolizin-1-yl)carbonyl)-3-ethoxypyrrolidine

HRID 1902145노트

반응식

HRID 1902145 반응식
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:14][CH2:13][N:12]3[C:7](=[C:8]([C:22]([OH:24])=O)[CH:9]=[C:10]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[C:11]3=[O:15])[C:6]=2[CH:25]=1.CN(C1C=CC=CN=1)C.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.Cl.[CH2:49]([O:51][C@H:52]1[CH2:56][CH2:55][NH:54][CH2:53]1)[CH3:50].C(O[C@H]1CCNC1)C>C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:14][CH2:13][N:12]3[C:7](=[C:8]([C:22]([N:54]4[CH2:55][CH2:56][C@H:52]([O:51][CH2:49][CH3:50])[CH2:53]4)=[O:24])[CH:9]=[C:10]([C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=4)[C:11]3=[O:15])[C:6]=2[CH:25]=1

참가 물질

8

반응물 6

HCID 8471Triethylamine2회HCID 218852-DimethylaminopyridineHCID 65578Oxalyl chlorideHCID 11116030(3S)-3-ethoxypyrrolidineHCID 1466674410-Chloro-4-oxo-3-phenyl-6,7-dihydro-4H-pyrido[2,1-A]isoquinoline-1-carboxylic acidHCID 67731241HCID 67731241, 화합물

생성물 1

HCID 3045375(S)-1-((10-chloro-6,7-dihydro-4-oxo-3-phenyl-4H-benzo(a)quinolizin-1-yl)carbonyl)-3-ethoxypyrrolidine수율 85%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

A suspension of 8.79 g (25 mmol) of 10-chloro-4-oxo-3-phenyl-6,7-dihydro-4H-benzo[a]quinolizine-1-carboxylic acid (X) in 125 ml of ethyl acetate was treated with 0.076 g (0.625 mmol) of dimethylaminopyridine and 3.49 g (27.5 mmol) of oxalyl chloride. The mixture was then stirred at 600 for 3 hours. The yellow solution (XI) was concentrated and the residue was taken up in 125 ml of toluene. This was treated either with 5.26 g (52 mmol) of triethylamine and 3.94 g (26 mmol) of (S)-3-ethoxypyrrolidine hydrochloride or with 2.63 g (26 mmol) of triethylamine and 3.0 g (26 mmol) of (S)-3-ethoxypyrrolidine and stirred for 4 hours. Subsequently, the solution was washed in succession with 100 ml of water, 100 ml of 1N HCl, 100 ml of 0.5N KHCO3 and then again with 100 ml of water. The individual aqueous phases were extracted with 100 ml of toluene and the combined organic extracts were dried with 20 g of Na2SO4. The residue obtained after filtration and concentration was dried at 50°/0.1 mbar/2 h. Compound I was obtained in 85% yield, based on the acid, after purification by recrystallization from acetone/water and acetone/hexane. M.p. 133°-134°.

후처리

  1. concentrationThe yellow solution (XI) was concentrated
  2. stirringstirred for 4 hours
  3. washSubsequently, the solution was washed in succession with 100 ml of water, 100 ml of 1N HCl, 100 ml of 0.5N KHCO3
  4. extractionThe individual aqueous phases were extracted with 100 ml of toluene
  5. dry with materialthe combined organic extracts were dried with 20 g of Na2SO4
  6. customThe residue obtained
  7. filtrationafter filtration and concentration
  8. customwas dried at 50°/0.1 mbar/2 h

출처 및 근거

ORD 기록
ord-48689e6983b64e96a04270082be6eb86
출처 데이터셋
uspto-grants-1996_11
특허 번호
US05578728

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