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 81264노트

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HRID 81264 반응식
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

참가 물질

7

반응물 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

생성물 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

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 8857Ethyl Acetate용매

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온도
90 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-02a22dbd50f143e884206c681ab88fc5
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846657B2

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