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

HRID 450444ノート

反応式

HRID 450444 の反応式
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]

参加物

6

反応物 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-

生成物 1

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

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-4e5d021c2df0486f9dd646b7d83cf504
出典データセット
uspto-grants-2013_07
特許番号
US08486951B2

反応ノート

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