Triethylamine → 3-[4-(Azetidin-1-ylcarbonyl)-2,5-difluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 20599

Reaktionsgleichung

Reaktionsgleichung von HRID 20599
[F:1][C:2]1[CH:10]=[C:9](F)[C:8]([F:12])=[CH:7][C:3]=1[C:4]([OH:6])=O.ClC(N(C)C)=C(C)C.C(N(CC)CC)C.Cl.[NH:29]1[CH2:32][CH2:31][CH2:30]1.[OH:33][C:34]1[CH:35]=[C:36]([CH:46]=[C:47]([O:49][C@@H:50]([CH3:53])[CH2:51][OH:52])[CH:48]=1)[C:37]([NH:39][C:40]1[CH:44]=[CH:43][N:42]([CH3:45])[N:41]=1)=[O:38].C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.Cl.C(#N)C>[N:29]1([C:4]([C:3]2[C:2]([F:1])=[CH:10][C:9]([O:33][C:34]3[CH:35]=[C:36]([CH:46]=[C:47]([O:49][C@@H:50]([CH3:53])[CH2:51][OH:52])[CH:48]=3)[C:37]([NH:39][C:40]3[CH:44]=[CH:43][N:42]([CH3:45])[N:41]=3)=[O:38])=[C:8]([F:12])[CH:7]=2)=[O:6])[CH2:32][CH2:31][CH2:30]1

Komponenten

10

Edukt 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 5211702,4,5-Trifluorobenzoic acidHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 12308726Azetidine hydrochlorideHCID 593468923-Hydroxy-5-{[(S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Produkt 1

HCID 116128053-[4-(Azetidin-1-ylcarbonyl)-2,5-difluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamideAusbeute 31,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 313Hydrochloric AcidLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
160 °C

Versuchsvorschrift

A solution of 2,4,5-trifluorobenzoic acid (123 mg, 0.7 mmol) in DCM (1.7 mL) was treated with (1-chloro-2-methylprop-1-en-1-yl)dimethylamine (103 mg, 0.77 mmol) and stirred under argon for 1 hour. The mixture was then treated with triethylamine (0.29 mL, 2.1 mmol) and azetidine hydrochloride (78 mg, 0.84 mmol), before being left to stir for 18 hours. The mixture was diluted with DCM (5 mL) and 2M hydrochloric acid (4 mL) and separated. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was treated with suspension of 3-hydroxy-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide (200 mg, 0.477 mmol) and potassium carbonate (284 mg, 2.05 mmol) in acetonitrile (3.5 mL) was heated in a microwave reactor at 160° C. for 1.5 hours. The reaction mixture was filtered and concentrated in vacuo. The residue was then chromatographed on silica, eluting with 0-15% methanol in ethylacetate, to give the title compound (74 mg).

Aufarbeitung

  1. waitbefore being left
  2. stirringto stir for 18 hours
  3. customseparated
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. filtrationThe reaction mixture was filtered
  8. concentrationconcentrated in vacuo
  9. customThe residue was then chromatographed on silica
  10. washeluting with 0-15% methanol in ethylacetate

Quellen und Nachweise

ORD-Eintrag
ord-ef98e1c7b4764eec9a3f724e10aa14e9
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745475B2

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