Diisopropylethylamine → 4,6-dichloro-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[4-(trifluoromethyl)benzyl]-3H-imidazo[4,5-c]pyridine

HRID 81264ノート

反応式

HRID 81264 の反応式
Br[C:2]1[N:12]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[C:5]2[C:6]([Cl:11])=[N:7][C:8]([Cl:10])=[CH:9][C:4]=2[N:3]=1.Cl.[O:25]1[CH2:30][CH2:29][NH:28][CH:27]2[CH2:31][CH2:32][CH2:33][CH:26]12.[F-].[K+].CCN(C(C)C)C(C)C>C(OCC)(=O)C.CS(C)=O>[Cl:11][C:6]1[C:5]2[N:12]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[C:2]([N:28]3[CH2:29][CH2:30][O:25][C@@H:26]4[CH2:33][CH2:32][CH2:31][C@@H:27]34)=[N:3][C:4]=2[CH:9]=[C:8]([Cl:10])[N:7]=1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 522689Potassium FluorideHCID 45792192Octahydrocyclopenta[b][1,4]oxazine hydrochlorideHCID 867246102-bromo-4,6-dichloro-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine

生成物 1

HCID 867246114,6-dichloro-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[4-(trifluoromethyl)benzyl]-3H-imidazo[4,5-c]pyridine

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

To a vial were added 2-bromo-4,6-dichloro-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine (200 mg, 0.47 mmol), octahydrocyclopenta[b][1,4]oxazine hydrochloride (purchased from Enamine); 147 mg, 0.9 mmol), potassium fluoride (81 mg, 1.41 mmol), DIEA (246 μL, 1.41 mmol), and DMSO (2 mL). The vial was sealed and heated to 90° C. for 1 hour. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and washed with water and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-60% ethyl acetate/hexanes, linear gradient) to afford 4,6-dichloro-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[4-(trifluoromethyl)benzyl]-3H-imidazo[4,5-c]pyridine (racemate). MS APCl calc'd. for C21H19Cl2F3N4O [M+H]+ 471. found 471.

後処理

  1. customThe vial was sealed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. washwashed with water and brine
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (0-60% ethyl acetate/hexanes, linear gradient)

出典と根拠

ORDレコード
ord-02a22dbd50f143e884206c681ab88fc5
出典データセット
uspto-grants-2014_09
特許番号
US08846657B2

反応ノート

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