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

HRID 864262ノート

反応式

HRID 864262 の反応式
[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

参加物

8

反応物 6

HCID 8471Triethylamine2 回HCID 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、化合物

生成物 1

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

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

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 (26mmol) 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°.

後処理

  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

出典と根拠

ORDレコード
ord-3e67d3dfcb2f4893b5629a2abf7b37d1
出典データセット
uspto-grants-1996_10
特許番号
US05561233

反応ノート

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