Diethyl Ether → 1-[1-(2-Dimethylaminoethyl)piperidin-4-yl]-3-[4-(4-{3-[2-(4-fluorophenyl)acetyl]ureido}phenoxy)pyridin-2-yl]-1-methylurea

HRID 492938Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 492938
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14](=[O:28])[N:15]([CH:17]3[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][N:25]([CH3:27])[CH3:26])[CH2:19][CH2:18]3)[CH3:16])[CH:8]=2)=[CH:4][CH:3]=1.[F:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38][C:39]([N:41]=[C:42]=[O:43])=[O:40])=[CH:34][CH:33]=1.C(OCC)C.CCCCCC>O1CCCC1>[CH3:27][N:25]([CH3:26])[CH2:24][CH2:23][N:20]1[CH2:21][CH2:22][CH:17]([N:15]([CH3:16])[C:14]([NH:13][C:9]2[CH:8]=[C:7]([O:6][C:5]3[CH:4]=[CH:3][C:2]([NH:1][C:42]([NH:41][C:39](=[O:40])[CH2:38][C:35]4[CH:36]=[CH:37][C:32]([F:31])=[CH:33][CH:34]=4)=[O:43])=[CH:30][CH:29]=3)[CH:12]=[CH:11][N:10]=2)=[O:28])[CH2:18][CH2:19]1

Komponenten

6

Edukt 4

HCID 3283Diethyl EtherHCID 8058HexaneHCID 231530882-(4-Fluorophenyl)acetyl isocyanateHCID 231531743-[4-(4-Aminophenoxy)pyridin-2-yl]-1-[1-(2-dimethylaminoethyl)piperidin-4-yl]-1-methylurea

Produkt 1

HCID 231535911-[1-(2-Dimethylaminoethyl)piperidin-4-yl]-3-[4-(4-{3-[2-(4-fluorophenyl)acetyl]ureido}phenoxy)pyridin-2-yl]-1-methylureaAusbeute 13,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a solution of 3-[4-(4-aminophenoxy)-pyridin-2-yl]-1-[1-(2-dimethylaminoethyl)piperidin-4-yl]-1-methylurea (154 mg) in tetrahydrofuran (5.0 ml) was added a solution of 2-(4-fluorophenyl)acetyl isocyanate in tetrahydrofuran (0.25 M, 3.73 ml) at room temperature, followed by stirring at room temperature for 10.5 hrs. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The 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=10:1). Fractions containing a target compound were concentrated to give a residue, to which diethyl ether (1 ml) and hexane (1 ml) were added to give a precipitate. The precipitate was filtered off, and dried under aeration to provide the titled compound (29.8 mg, 13.5%) as white powder.

Aufarbeitung

  1. customThe reaction mixture was partitioned between ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationThe organic layer was concentrated
  5. customto give a residue, which
  6. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent
  7. additionFractions containing a target compound
  8. concentrationwere concentrated
  9. customto give a residue
  10. customto give a precipitate
  11. filtrationThe precipitate was filtered off
  12. customdried under aeration

Quellen und Nachweise

ORD-Eintrag
ord-b8f5acedac334edba52f4167e87fe2e8
Quelldatensatz
uspto-grants-2009_05
Patentnummer
US07531532B2

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