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

HRID 492969
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HRID 492969 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.[F:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][C:37]([N:39]=[C:40]=[O:41])=[O:38])=[CH:32][CH:31]=1.C(OCC)C>O1CCCC1.C(OCC)(=O)C>[F:29][C:30]1[CH:31]=[CH:32][C:33]([CH2:36][C:37]([NH:39][C:40](=[O:41])[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:38])=[CH:34][CH:35]=1
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참가 물질

6

반응물 3

HCID 3283Diethyl EtherHCID 231530882-(4-Fluorophenyl)acetyl isocyanateHCID 576774204-(1-Methylazetidin-3-yl)piperazine-1-carboxylic acid [4-(4-aminophenoxy)pyridin-2-yl]amide

생성물 1

HCID 576774014-(1-Methylazetidin-3-yl)piperazine-1-carboxylic acid [4-(4-{3-[2-(4-fluorophenyl)acetyl]ureido}phenoxy)pyridin-2-yl]amide수율 48%

시약·촉매·용매 2

HCID 8028
Tetrahydrofuran
용매
HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 4-(1-methylazetidin-3-yl)piperazine-1-carboxylic acid [4-(4-aminophenoxy)pyridin-2-yl]amide (100 mg) in tetrahydrofuran (5.0 ml) was added a solution of 2-(4-fluorophenyl)acetyl isocyanate in ethyl acetate (0.25 M, 2.61 ml) at room temperature, followed by stirring at room temperature for 4.5 hrs. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. 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:methanol=100:7). Fractions containing a target compound were concentrated to give a residue, to which diethyl ether was added to give a precipitate. The precipitate was suspended in the solvent. Then the precipitate was filtered off, washed with diethyl ether, and dried under aeration to provide the titled compound (70.4 mg, 48.0%) as pale yellow powder.

후처리

  1. customThe reaction mixture was partitioned between ethyl acetate
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationThe organic layer was concentrated
  6. customto give a residue, which
  7. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate:methanol=100:7)
  8. additionFractions containing a target compound
  9. concentrationwere concentrated
  10. customto give a residue
  11. customto give a precipitate
  12. filtrationThen the precipitate was filtered off
  13. washwashed with diethyl ether
  14. customdried under aeration

출처 및 근거

ORD 기록
ord-2c45b97616764515b0cf06ef52c94f9b
출처 데이터셋
uspto-grants-2009_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07531532B2

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