Phenylacetyl isocyanate → Morpholine-4-carboxylic acid {4-[2-fluoro-4-(3-phenylacetylureido)phenoxy]pyridin-2-yl}amide

HRID 492807Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 492807
[NH2:1][C:2]1[CH:23]=[CH:22][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][O:19][CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[C:4]([F:24])[CH:3]=1.[C:25]1([CH2:31][C:32]([N:34]=[C:35]=[O:36])=[O:33])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN(C)C=O.FC1C=C(NC(NC(=O)CC2C=CC=CC=2)=S)C=CC=1OC1N=CN=C(NC(N2CCCC2)=O)C=1.C(OCC)(=O)C>[F:24][C:4]1[CH:3]=[C:2]([NH:1][C:35]([NH:34][C:32](=[O:33])[CH2:31][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:36])[CH:23]=[CH:22][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]2[CH2:17][CH2:18][O:19][CH2:20][CH2:21]2)=[O:15])[CH:8]=1

Komponenten

6

Edukt 2

HCID 12259960Phenylacetyl isocyanateHCID 57677752N-(4-(4-amino-2-fluorophenoxy)pyridin-2-yl)morpholine-4-carboxamide

Produkt 1

HCID 57677500Morpholine-4-carboxylic acid {4-[2-fluoro-4-(3-phenylacetylureido)phenoxy]pyridin-2-yl}amideAusbeute 12 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 11248939Pyrrolidine-1-carboxylic acid {6-[2-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyrimidin-4-yl}amideLösungsmittel

Versuchsvorschrift

To a solution of morpholine-4-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide (54 mg) in N,N-dimethylformamide (1.0 ml) was added a solution of phenylacetyl isocyanate in hexane (0.972 ml, Production Example 1), followed by stirring at room temperature for 25 hrs. The reaction mixture was partitioned between ethyl acetate (50 ml) and water (30 ml). The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:1 to 1:2, ethyl acetate, ethyl acetate:methanol=20:1 to 10:1). Fractions containing the target compound were concentrated to give a solid, which was suspended in ethyl acetate. The solid was filtered off, washed with ethyl acetate, and dried under aeration to provide the titled compound (9.5 mg, 12%) as colorless powder.

Aufarbeitung

  1. customThe reaction mixture was partitioned between ethyl acetate (50 ml) and water (30 ml)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated
  5. customto give a residue, which
  6. customwas then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:1 to 1:2, ethyl acetate, ethyl acetate:methanol=20:1 to 10:1)
  7. additionFractions containing the target compound
  8. concentrationwere concentrated
  9. customto give a solid, which
  10. filtrationThe solid was filtered off
  11. washwashed with ethyl acetate
  12. customdried under aeration

Quellen und Nachweise

ORD-Eintrag
ord-df66b798e50740588604c3b2122cdee4
Quelldatensatz
uspto-grants-2009_05
Patentnummer
US07531532B2

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