Ammonium Chloride → 2-Cyclopropyl-6-(3,5-difluorophenyl)-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile

HRID 17451

반응식

HRID 17451 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].[F:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[C:23]([F:25])[CH:24]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Cl-].[NH4+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[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:21]4[CH:20]=[C:19]([F:18])[CH:24]=[C:23]([F:25])[CH:22]=4)[C:3]=3[F:17])[N:6]=2)[CH2:11][CH2:10]1

참가 물질

7

반응물 4

HCID 25517Ammonium ChlorideHCID 62657Potassium Phosphate, TribasicHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 510414276-Bromo-2-cyclopropyl-7-fluoro-5-methylbenzoxazole-4-carbonitrile

생성물 1

HCID 685854282-Cyclopropyl-6-(3,5-difluorophenyl)-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

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온도
95 °C

실험 절차

6-Bromo-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile (I-77) (200 mg, 0.68 mmol), 3,5-difluorophenylboronic acid (428 mg, 2.71 mmol) and tripotassium phosphate (288 mg, 1.36 mmol) were dissolved in 1,4-dioxane (8 ml), then at room temperature, tetrakis(triphenylphosphine)palladium(0) (157 mg, 0.14 mmol) was added. The solution was stirred under nitrogen atmosphere at 95° C. for 60 hours. After cooling to room temperature, aqueous saturated ammonium chloride solution was added to the reaction liquid, followed by stirring at room temperature for 5 minutes. This was extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the solvent was evaporated away, and the resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=8:1) to obtain the entitled compound (240.5 mg containing impurities (reference)) as a white solid. Since the impurities were difficult to separate, they are separated in the next step.

후처리

  1. temperatureAfter cooling to room temperature
  2. stirringby stirring at room temperature for 5 minutes
  3. extractionThis was extracted twice with ethyl acetate
  4. washwashed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe insoluble matter was separated by filtration
  7. customthe solvent was evaporated away
  8. customthe resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=8:1)
  9. customto obtain
  10. additionthe entitled compound (240.5 mg containing impurities (reference)) as a white solid
  11. customto separate
  12. customthey are separated in the next step

출처 및 근거

ORD 기록
ord-194f026f7f054f48964c549dadb82382
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07737166B2

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