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(1S)-(+)-Camphor-10-sulphonic acid → 4-(1-Methylazetidin-3-yl)piperazine-1-carboxylic acid {4-[4-(3-phenylacetylthioureido)phenoxy]pyridin-2-yl}amide

HRID 492967
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HRID 492967 반응식
[NH2:1][C:2]1[CH:28]=[CH:27][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]3[CH2:21][CH2:20][N:19]([CH:22]4[CH2:25][N:24]([CH3:26])[CH2:23]4)[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[CH:4][CH:3]=1.[C@]12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.[C:44]1([CH2:50][C:51]([N:53]=[C:54]=[S:55])=[O:52])[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.C(=O)([O-])O.[Na+]>C(O)C.C1(C)C=CC=CC=1.CCCCCC.C(OCC)C.C(OCC)(=O)C.O1CCCC1>[C:44]1([CH2:50][C:51]([NH:53][C:54](=[S:55])[NH:1][C:2]2[CH:28]=[CH:27][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]4[CH2:21][CH2:20][N:19]([CH:22]5[CH2:23][N:24]([CH3:26])[CH2:25]5)[CH2:18][CH2:17]4)=[O:15])[CH:8]=3)=[CH:4][CH:3]=2)=[O:52])[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

11

반응물 4

HCID 218580(1S)-(+)-Camphor-10-sulphonic acidHCID 516892Sodium BicarbonateHCID 12454157Phenylacetyl isothiocyanateHCID 576774204-(1-Methylazetidin-3-yl)piperazine-1-carboxylic acid [4-(4-aminophenoxy)pyridin-2-yl]amide

생성물 1

HCID 576776394-(1-Methylazetidin-3-yl)piperazine-1-carboxylic acid {4-[4-(3-phenylacetylthioureido)phenoxy]pyridin-2-yl}amide
수율 23.3%

시약·촉매·용매 6

HCID 702Ethanol용매HCID 1140Toluene용매HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매HCID 8058Hexane용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 4-(1-methylazetidin-3-yl)piperazine-1-carboxylic acid [4-(4-aminophenoxy)pyridin-2-yl]amide (130 mg) in ethanol (6.0 ml)-tetrahydrofuran (6.0 ml) was added (1S)-(+)-10-camphorsulfonic acid (150 mg), followed by stirring at room temperature for 15 min. A solution of 2-phenylacetyl isothiocyanate in toluene (0.25 M, 4.08 ml) was added to the reaction mixture, followed by stirring at room temperature for 2 hrs. Ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (20 ml) were added to the reaction mixture, and the organic layer was separated. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, and dried over anhydrous sodium sulfate. The organic layer was concentrated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=20:1). Fractions containing the titled compound were concentrated to give a residue, to which diethyl ether (5 ml) and hexane (10 ml) were added to give a precipitate. The precipitate was suspended in the solvent. Then the precipitate was filtered off, washed with hexane, and dried under aeration to provide the titled compound (44.3 mg, 23.3%) as pale yellow powder.

후처리

  1. stirringby stirring at room temperature for 2 hrs
  2. customthe organic layer was separated
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationThe organic layer was concentrated
  7. customto give a residue, which
  8. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent
  9. additionFractions containing the titled compound
  10. concentrationwere concentrated
  11. customto give a residue
  12. customto give a precipitate
  13. filtrationThen the precipitate was filtered off
  14. washwashed with hexane
  15. customdried under aeration

출처 및 근거

ORD 기록
ord-b4d13e30849b43059ce99ded8aaa95e8
출처 데이터셋
uspto-grants-2009_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07531532B2

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