Thionyl Chloride → 4-(4-Dimethylcarbamoyl-3-fluoro-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (5-methyl-isoxazol-3-yl)-amide

HRID 1177123Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1177123
[CH3:1][N:2]([CH3:27])[C:3]([C:5]1[CH:25]=[CH:24][C:8]([O:9][C:10]2[C:15]3[CH2:16][C:17]([CH3:20])([CH3:19])[O:18][C:14]=3[CH:13]=[C:12]([C:21]([OH:23])=O)[CH:11]=2)=[CH:7][C:6]=1[F:26])=[O:4].S(Cl)(Cl)=O.[NH2:32][C:33]1[CH:37]=[C:36]([CH3:38])[O:35][N:34]=1>C(Cl)Cl.CN(C=O)C.CN(C1C=CN=CC=1)C>[CH3:38][C:36]1[O:35][N:34]=[C:33]([NH:32][C:21]([C:12]2[CH:11]=[C:10]([O:9][C:8]3[CH:24]=[CH:25][C:5]([C:3](=[O:4])[N:2]([CH3:1])[CH3:27])=[C:6]([F:26])[CH:7]=3)[C:15]3[CH2:16][C:17]([CH3:19])([CH3:20])[O:18][C:14]=3[CH:13]=2)=[O:23])[CH:37]=1

Komponenten

7

Edukt 3

HCID 24386Thionyl ChlorideHCID 661723-Amino-5-methylisoxazoleHCID 595604114-(4-Dimethylcarbamoyl-3-fluoro-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid

Produkt 1

HCID 595600814-(4-Dimethylcarbamoyl-3-fluoro-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (5-methyl-isoxazol-3-yl)-amideAusbeute 10 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideKatalysatorHCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

To a solution of 4-(4-dimethylcarbamoyl-3-fluoro-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (143a) (66 mg, 0.177 mmol) in 3 mL of CH2Cl2 was added thionyl chloride (0.0154 mL, 0.212 mmol), followed by 3 drops of DMF. The mixture was refluxed for 1.5 h, then concentrated and dried under vacuum. The residue was dissolved in 3 mL of CH2Cl2, added 3-amino-5-methylisoxazole (22.6 mg, 0.230 mmol) at 0° C., followed by DMAP (52 mg, 0.354 mmol). The mixture was stirred at 0° C. to room temperature for 1 hr and heated at 40° C. overnight, then concentrated and purified by flash column chromatography with 40-55% EtOAc in hexanes to give a white solid (8 mg, 10% yield). 1H NMR (400 MHz, CDCl3) δ 9.06 (s, 1 H) 7.38 (t, J=8.08 Hz, 1 H) 7.11 (d, J=1.77 Hz, 2 H) 6.76-6.84 (m, 2 H) 6.70 (dd, J=10.61, 2.27 Hz, 1 H) 3.13 (s, 3 H) 2.98 (br. s., 3 H) 2.91 (s, 2 H) 2.42 (s, 3 H) 1.50 (s, 6 H); LCMS for C24H24FN3O5 m/z 454.00 (M+H+).

Aufarbeitung

  1. temperatureThe mixture was refluxed for 1.5 h
  2. concentrationconcentrated
  3. customdried under vacuum
  4. dissolutionThe residue was dissolved in 3 mL of CH2Cl2
  5. concentrationconcentrated
  6. custompurified by flash column chromatography with 40-55% EtOAc in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-15758b0b227b4b3e81526f906759ef0f
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07842713B2

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