Sodium hydride → (S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-(4-fluorobenzylidene)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide

HRID 1630291노트

반응식

HRID 1630291 반응식
[Cl-].[F:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7]P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=[CH:5][CH:4]=1.[H-].[Na+].[N:31]1([CH2:36][C:37]([N:39]2[CH2:43][C:42](=O)[CH2:41][C@H:40]2[C:45]([NH:47][C:48]2[CH:53]=[CH:52][C:51]([O:54][C:55]3[CH:60]=[CH:59][C:58]([F:61])=[CH:57][CH:56]=3)=[CH:50][CH:49]=2)=[O:46])=[O:38])[CH:35]=[N:34][CH:33]=[N:32]1>CS(C)=O>[N:31]1([CH2:36][C:37]([N:39]2[CH2:43][C:42](=[CH:7][C:6]3[CH:5]=[CH:4][C:3]([F:2])=[CH:28][CH:27]=3)[CH2:41][C@H:40]2[C:45]([NH:47][C:48]2[CH:53]=[CH:52][C:51]([O:54][C:55]3[CH:56]=[CH:57][C:58]([F:61])=[CH:59][CH:60]=3)=[CH:50][CH:49]=2)=[O:46])=[O:38])[CH:35]=[N:34][CH:33]=[N:32]1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 56954158(S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-oxopyrrolidine-2-carboxamideHCID 178505801HCID 178505801, 화합물

생성물 1

HCID 67009559(S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-(4-fluorobenzylidene)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide수율 11%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매3회

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온도
70 °C

실험 절차

Step (b) 4-Fluorobenzyl triphenylphosphine chloride (1 g, 2.46 mmol) in DMSO (2 mL) was added to a flask charged with sodium hydride (60% dispersion in oil, 124 mg, 3.10 mmol) and DMSO (2 mL). The reaction mixture was stirred at 70° C. for 3 hours and then (S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-oxopyrrolidine-2-carboxamide (0.11 g, 0.25 mmol) in DMSO (2 mL) was added. The mixture was stirred for 16 hours at 70° C. and then quenched with saturated ammonium chloride (aq., 10 mL). This mixture was extracted with ethyl acetate (20 mL) and the extract was washed with deionized water (10 mL). Product was purified from the mixture directly by column chromatography (EtOAc to EtOAc/MeOH (9:1)+1% NEt3) to give with (S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-(4-fluorobenzylidene)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (15 mg, 0.027 mmol, 11% yield) as an oil.

후처리

  1. stirringThe mixture was stirred for 16 hours at 70° C.
  2. customquenched with saturated ammonium chloride (aq., 10 mL)
  3. extractionThis mixture was extracted with ethyl acetate (20 mL)
  4. washthe extract was washed with deionized water (10 mL)
  5. customProduct was purified from the mixture directly by column chromatography (EtOAc to EtOAc/MeOH (9:1)+1% NEt3)

출처 및 근거

ORD 기록
ord-52204468990848df8fcaee1c8dbe1907
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08791102B2

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