Diethyl Ether → 4-[2-(Azetidin-1-yl)ethyl]piperazine-1-carboxylic acid [4-(4-{3-[2-(4fluorophenyl)acetyl]thioureido}phenoxy)pyridin-2-yl]amide

HRID 493007노트

반응식

HRID 493007 반응식
[NH2:1][C:2]1[CH:29]=[CH:28][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]([CH2:22][CH2:23][N:24]4[CH2:27][CH2:26][CH2:25]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.[F:45][C:46]1[CH:51]=[CH:50][C:49]([CH2:52][C:53]([N:55]=[C:56]=[S:57])=[O:54])=[CH:48][CH:47]=1.C(OCC)C>C(O)C.C1(C)C=CC=CC=1.CCCCCC>[F:45][C:46]1[CH:47]=[CH:48][C:49]([CH2:52][C:53]([NH:55][C:56](=[S:57])[NH:1][C:2]2[CH:3]=[CH:4][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]([CH2:22][CH2:23][N:24]5[CH2:27][CH2:26][CH2:25]5)[CH2:18][CH2:17]4)=[O:15])[CH:8]=3)=[CH:28][CH:29]=2)=[O:54])=[CH:50][CH:51]=1

참가 물질

8

반응물 4

HCID 3283Diethyl EtherHCID 218580(1S)-(+)-Camphor-10-sulphonic acidHCID 231532482-(4-Fluorophenyl)acetyl isothiocyanateHCID 576775264-[2-(Azetidin-1-yl)ethyl]piperazine-1-carboxylic acid [4-(4-aminophenoxy)pyridin-2-yl]amide

생성물 1

HCID 114902404-[2-(Azetidin-1-yl)ethyl]piperazine-1-carboxylic acid [4-(4-{3-[2-(4fluorophenyl)acetyl]thioureido}phenoxy)pyridin-2-yl]amide수율 36.2%

시약·촉매·용매 3

HCID 702Ethanol용매HCID 1140Toluene용매HCID 8058Hexane용매

실험 절차

4-[2-(Azetidin-1-yl)ethyl]piperazine-1-carboxylic acid [4-(4-aminophenoxy)pyridin-2-yl]amide (63 mg) was dissolved in ethanol (1.5 ml) under a nitrogen atmosphere, and then (S)-(+)-10-camphorsulfonic acid (111 mg) was added thereto, followed by stirring for 5 min. A 0.25 M solution of 2-(4-fluorophenyl)acetyl isothiocyanate in toluene (0.954 ml) was added thereto, followed by stirring for 13.5 hrs. The reaction mixture was partitioned between ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (30 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (30 ml), water (30 ml), brine (30 ml) in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; heptane:ethyl acetate=1:8, ethyl acetate, then ethyl acetate:ethanol=95:5). Fractions containing the target compound were concentrated under reduced pressure to give a residue, to which diethyl ether (2 ml) and hexane (2 ml) were then added to suspend. The solid was filtered off, and dried under aeration to provide the titled compound (34.1 mg, 36.2%) as white powder.

후처리

  1. stirringby stirring for 13.5 hrs
  2. customThe reaction mixture was partitioned between ethyl acetate (50 ml)
  3. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (30 ml), water (30 ml), brine (30 ml) in this order
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated
  6. customto give a residue, which
  7. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent
  8. additionFractions containing the target compound
  9. concentrationwere concentrated under reduced pressure
  10. customto give a residue
  11. filtrationThe solid was filtered off
  12. customdried under aeration

출처 및 근거

ORD 기록
ord-4d9e808986984df19665f36f64f8d744
출처 데이터셋
uspto-grants-2009_05
특허 번호
US07531532B2

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