2-(Tributylstannyl)pyridine → 2-Cyclopropyl-7-fluoro-5-methyl-6-(2-pyridyl)-1,3-benzoxazole-4-carbonitrile

HRID 17333

반응식

HRID 17333 반응식
Br[C:2]1[C:3]([F:17])=[C:4]2[O:8][C:7]([CH:9]3[CH2:11][CH2:10]3)=[N:6][C:5]2=[C:12]([C:15]#[N:16])[C:13]=1[CH3:14].C([Sn](CCCC)(CCCC)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1)CCC>C1(C)C=CC=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(C1(C)C(O)=C(C(C)(C)C)C=CC1)(C)(C)C>[CH:9]1([C:7]2[O:8][C:4]3[C:5](=[C:12]([C:15]#[N:16])[C:13]([CH3:14])=[C:2]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)[C:3]=3[F:17])[N:6]=2)[CH2:11][CH2:10]1

참가 물질

6

반응물 2

HCID 6077842-(Tributylstannyl)pyridineHCID 510414276-Bromo-2-cyclopropyl-7-fluoro-5-methylbenzoxazole-4-carbonitrile

생성물 1

HCID 510423332-Cyclopropyl-7-fluoro-5-methyl-6-(2-pyridyl)-1,3-benzoxazole-4-carbonitrile수율 92.6%

시약·촉매·용매 3

HCID 666371922,6-Di-t-butylcresol촉매HCID 178418476HCID 178418476, 화합물촉매HCID 1140Toluene용매

실험 절차

6-Bromo-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile (I-77) (200 mg, 0.68 mmol) was dissolved in toluene (4 ml), then 2-tributylstannylpyridine (299 mg, 0.81 mmol) and 2,6-di-tert-butylcresol (2 mg) and bis(triphenylphosphine)palladium(II) dichloride (24 mg, 0.03 mmol) were added, followed by heating under reflux for 17 hours under nitrogen atmosphere. The reaction liquid was cooled, the insoluble matter was separated by filtration through Celite, the solvent was concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography, followed by removing tin-derived side products with n-hexane and by elution with a mixed solvent of n-hexane/ethyl acetate (5:1-3:1, v/v) to obtain 2-cyclopropyl-7-fluoro-5-methyl-6-(2-pyridyl)-1,3-benzoxazole-4-carbonitrile (184 mg, 0.63 mmol, 92%) as a pale yellow transparent oily substance, A part of this (183 mg, 0.62 mmol) was dissolved in dimethyl sulfoxide (3.7 ml), triethylamine (219 μl, 1.56 mmol) and (3S)-3-(dimethylamino)pyrrolidine (103 μl, 0.81 mmol) were added, followed by stirring at 90° C. under nitrogen atmosphere for 15 hours. After cooling to room temperature, ethyl acetate was added, followed by fractionation with water. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated away, the resulting residue was recrystallized and purified with a mixed solvent of diisopropyl ether/n-hexane/ethyl acetate to obtain the entitled compound (108 mg, 45%) as a pale brown solid.

후처리

  1. temperatureby heating
  2. temperatureunder reflux for 17 hours under nitrogen atmosphere
  3. customThe reaction liquid
  4. temperaturewas cooled
  5. customthe insoluble matter was separated by filtration through Celite
  6. concentrationthe solvent was concentrated under reduced pressure
  7. customby removing tin-
  8. washby elution with a mixed solvent of n-hexane/ethyl acetate (5:1-3:1

출처 및 근거

ORD 기록
ord-add1b74c3a83454489c921cafec7081f
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07737166B2

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