Sodium hydride → 1,3-dihydro-3,3-bis(2-fluoro-4-pyridinylmethyl)-1-(4-morpholinyl)-2H-indol-2-one

HRID 440442노트

반응식

HRID 440442 반응식
[H-].[Na+].[N:3]1([N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11][C:10]2=[O:18])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.[F:19][C:20]1[CH:25]=[C:24]([CH2:26]Cl)[CH:23]=[CH:22][N:21]=1>O1CCCC1>[F:19][C:20]1[CH:25]=[C:24]([CH2:26][C:11]2([CH2:26][C:24]3[CH:23]=[CH:22][N:21]=[C:20]([F:19])[CH:25]=3)[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:9]([N:3]3[CH2:4][CH2:5][O:6][CH2:7][CH2:8]3)[C:10]2=[O:18])[CH:23]=[CH:22][N:21]=1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 108445134-(Chloromethyl)-2-fluoropyridineHCID 152843961,3-dihydro-1-(4-morpholinyl)-2H-indol-2-one

생성물 1

HCID 99546911,3-dihydro-3,3-bis(2-fluoro-4-pyridinylmethyl)-1-(4-morpholinyl)-2H-indol-2-one

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

Sodium hydride (60% oil dispension 92 mg, 2.3 mmole) was charged to a flame-dried flask and washed with pentane (3×3 ml). The flask was flushed with nitrogen, tetrahydrofuran (10 ml) was added and the slurry was stirred at 0° C. 1,3-dihydro-1-(4-morpholinyl)-2H-indol-2-one (225 mg, 1.0 mmole) was added, the resulting solution was stirred for 15 minutes at room temperature and recooled to 0° C. A solution of 2-Fluoro-4-picolyl chloride (410 mg, 2.3 mmole) in tetrahydrofuran (10 ml) was added and the solution allowed to stir at room temperature overnight. The reaction was quenched into water (40 ml) and extracted with dichloromethane(3×25 ml). The combined organics were washed with brine, dried over magnesium sulfate, filter and concentrated under reduced pressure. The residue was chromatographed on silica gel or directly recrystallized from chloroform/hexane to give the desired product; m.p. 198°-203° C. Anal. (C24H22F2N4O2.0.25H2O): C,H,N,F.

후처리

  1. washwashed with pentane (3×3 ml)
  2. customThe flask was flushed with nitrogen, tetrahydrofuran (10 ml)
  3. additionwas added
  4. stirringthe resulting solution was stirred for 15 minutes at room temperature
  5. customrecooled to 0° C
  6. stirringto stir at room temperature overnight
  7. customThe reaction was quenched into water (40 ml)
  8. extractionextracted with dichloromethane(3×25 ml)
  9. washThe combined organics were washed with brine
  10. dry with materialdried over magnesium sulfate
  11. filtrationfilter
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was chromatographed on silica gel
  14. customdirectly recrystallized from chloroform/hexane

출처 및 근거

ORD 기록
ord-a56a44d8b4f64236b96b640d44184313
출처 데이터셋
uspto-grants-1996_05
특허 번호
US05519132

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