Dimethylformamide → (S)-3-[4-(2-butoxyethoxy)phenyl]-10-propyl-N-[4-[[(1-propyl-1H-imidazol-5-yl)methyl]sulfinyl]phenyl]-7,8,9,10-tetrahydropyrido[2,3-b]azocine-6-carboxamide

HRID 1182356노트

반응식

HRID 1182356 반응식
[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:32]=[N:31][C:18]3[N:19]([CH2:28][CH2:29][CH3:30])[CH2:20][CH2:21][CH2:22][C:23]([C:25](O)=[O:26])=[CH:24][C:17]=3[CH:16]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].CN(C=O)C.C(Cl)(=O)C(Cl)=O.[CH2:44]([N:47]1[C:51]([CH2:52][S@@:53]([C:55]2[CH:61]=[CH:60][C:58]([NH2:59])=[CH:57][CH:56]=2)=[O:54])=[CH:50][N:49]=[CH:48]1)[CH2:45][CH3:46]>ClCCl.O1CCCC1.O.N1C=CC=CC=1>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:32]=[N:31][C:18]3[N:19]([CH2:28][CH2:29][CH3:30])[CH2:20][CH2:21][CH2:22][C:23]([C:25]([NH:59][C:58]4[CH:60]=[CH:61][C:55]([S@:53]([CH2:52][C:51]5[N:47]([CH2:44][CH2:45][CH3:46])[CH:48]=[N:49][CH:50]=5)=[O:54])=[CH:56][CH:57]=4)=[O:26])=[CH:24][C:17]=3[CH:16]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]

참가 물질

9

반응물 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 11308257(S)-4-(((1-Propyl-1H-imidazol-5-yl)methyl)sulfinyl)anilineHCID 694282083-[4-(2-Butoxyethoxy)phenyl]-10-propyl-7,8,9,10-tetrahydropyrido[2,3-b]azocine-6-carboxylic acid

생성물 1

HCID 69427392(S)-3-[4-(2-butoxyethoxy)phenyl]-10-propyl-N-[4-[[(1-propyl-1H-imidazol-5-yl)methyl]sulfinyl]phenyl]-7,8,9,10-tetrahydropyrido[2,3-b]azocine-6-carboxamide

시약·촉매·용매 4

HCID 962Water용매HCID 1049Pyridine용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

(S)-4-(((1-propylimidazol-5-yl)methyl)sulfinyl)aniline di-p-toluoyl-D-tartrate monohydrate (495 mg) was dissolved in ethyl acetate (5 ml) and 1 N hydrochloric acid (2.52 ml), followed by separation. To the aqueous layer was added an aqueous 25% potassium carbonate solution (2.52 ml), followed by extraction with 2-propanol-ethyl acetate (1:4) twice. The organic layers were combined, washed with saturated brine and dried over magnesium sulfate, and then the solvent was distilled off under reduced pressure. To the resulting residue was added tetrahydrofuran, and then the solvent was again distilled off under reduced pressure to give (S)-(4-(((1-propylimidazol-5-yl)methyl)sulfinyl)aniline. Then, to a solution of 3-[4-(2-butoxyethoxy)phenyl]-10-propyl-7,8,9,10-tetrahydropyrido[2,3-b]azocine-6-carboxylic acid (250 mg) in dichloromethane (10 ml) were added a drop of DMF, and then oxalyl chloride (0.065 ml) at 0° C. The mixture was returned to room temperature and stirred for 30 minutes under a nitrogen atmosphere, and then the resulting solution was added dropwise to a solution of (S)-4-(((1-propylimidazol-5-yl)methyl)sulfinyl)aniline and pyridine (1.2 ml) in tetrahydrofuran (10 ml) at 0° C. under a nitrogen atmosphere. The mixture was returned to room temperature and stirred overnight. Then, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with water twice and saturated brine once, and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and then the residue was separated and purified by basic silica gel column chromatography (ethyl acetate→methanol:ethyl acetate=3:100) to give (S)-3-[4-(2-butoxyethoxy)phenyl]-10-propyl-N-[4-[[(1-propyl-1H-imidazol-5-yl)methyl]sulfinyl]phenyl]-7,8,9,10-tetrahydropyrido[2,3-b]azocine-6-carboxamide (310 mg) (Compound 2) as a yellow amorphous material.

후처리

  1. customat 0° C
  2. customwas returned to room temperature
  3. customwas returned to room temperature
  4. stirringstirred overnight
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with water twice
  7. dry with materialsaturated brine once, and then dried over magnesium sulfate
  8. distillationThe solvent was distilled off under reduced pressure
  9. customthe residue was separated
  10. custompurified by basic silica gel column chromatography (ethyl acetate→methanol:ethyl acetate=3:100)

출처 및 근거

ORD 기록
ord-c15c45531d2441709cc536ce908db688
출처 데이터셋
uspto-grants-2007_10
특허 번호
US07288654B2

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