Potassium Phosphate, Tribasic → 2,5-difluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline

HRID 450444노트

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HRID 450444 반응식
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:15]([F:16])=[CH:14][C:12]([NH2:13])=[C:11]([F:17])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[CH3:18][N:19]1[CH:23]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:21]=[N:20]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.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>[F:17][C:11]1[CH:10]=[C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([C:22]3[CH:21]=[N:20][N:19]([CH3:18])[CH:23]=3)[CH:7]=2)[C:15]([F:16])=[CH:14][C:12]=1[NH2:13]

참가 물질

6

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 78358387Benzenamine, 4-[(2-chloro-4-pyridinyl)oxy]-2,5-difluoro-

생성물 1

HCID 593227742,5-difluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline수율 63%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매

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온도
90 °C

실험 절차

To a solution of 4-(2-chloropyridin-4-yloxy)-2,5-difluoroaniline (450 mg, 1.76 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (400 mg, 1.9 mmol) in N,N-dimethylformamide (30 mL) was added tetrakis(triphenylphosphine)palladium (105 mg, 0.09 mmol) and an aqueous solution of potassium phosphate (2 M, 1.8 mL). The mixture was flushed with nitrogen for 10 min, and then stirred with heating at 90° C. under nitrogen overnight. After cooling to RT, the reaction mixture was partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with brine, dried (Na2SO4), concentrated under reduced pressure and purified by column chromatography on silica gel to give 2,5-difluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)aniline (335 mg, 63% yield). 1H NMR (300 MHz, DMSO-d6): δ 8.35 (d, J=5.7 Hz, 1H), 8.27 (s, 1H), 7.98 (s, 1H), 7.24-7.18 (m, 2H), 6.75 (dd, J=12.3, 8.1 Hz, 1H), 6.62 (dd, J=5.4, 2.1 Hz, 1H), 5.53 (br s, 2 E), 3.87 (s, 3H); MS (ESI): m/z 303.1 [M+1]+.

후처리

  1. customThe mixture was flushed with nitrogen for 10 min
  2. temperatureAfter cooling to RT
  3. customthe reaction mixture was partitioned between water and ethyl acetate
  4. extractionThe aqueous layer was extracted with ethyl acetate (50 mL×3)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. custompurified by column chromatography on silica gel

출처 및 근거

ORD 기록
ord-4e5d021c2df0486f9dd646b7d83cf504
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08486951B2

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