Water → 5-chloro-2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine

HRID 450450

반응식

HRID 450450 반응식
[Cl:1][C:2]1[C:3]([O:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13](Cl)[CH:12]=2)=[CH:4][C:5]([F:9])=[C:6]([NH2:8])[CH:7]=1.[CH3:18][N:19]1[CH:23]=[CH:22][C:21](B2OC(C)(C)C(C)(C)O2)=[N:20]1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[Cl:1][C:2]1[C:3]([O:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13]([C:22]3[CH:21]=[N:20][N:19]([CH3:18])[CH:23]=3)[CH:12]=2)=[CH:4][C:5]([F:9])=[C:6]([NH2:8])[CH:7]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27600771-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 866416885-Chloro-4-(2-chloropyridin-4-yloxy)-2-fluorobenzenamine

생성물 1

HCID 673986315-chloro-2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine수율 77.3%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
90 °C

실험 절차

5-Chloro-4-(2-chloropyridin-4-yloxy)-2-fluorobenzenamine (1.177 g, 4.31 mmol) and 1-methyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.166 g, 5.60 mmol) were dissolved in DMF (16.16 ml), cesium carbonate (4.21 g, 12.93 mmol) was added, followed by water (5.39 ml). Argon was bubbled through the mixture for 5 minutes, and then palladium tetrakistriphenylphosphine (0.249 g, 0.215 mmol) was added. The flask was fitted with a reflux condenser, flushed with argon, and heated in a 90° C. oil bath under a balloon of argon for 4 hours. The reaction mixture was then cooled to RT and diluted with a 4:1 mixture of ethyl acetate and THF. The solution was extracted with 10% aqueous LiCl (2×150 mL) and brine (100 mL), dried (MgSO4), evaporated under reduced pressure and purified via silica gel chromatography (ethyl acetate/hexanes) to yield 5-chloro-2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine as a tan solid (1.062 g, 77% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.31 (d, 1H), 8.24 (s, 1H), 7.95 (s, 1H), 7.20 (d, 1H), 7.13 (d, 1H), 6.92 (d, 1H), 6.52 (dd, 1H), 5.49 (s, 2H), 3.84 (s, 3H); MS (ESI) m/z: 319.1 (M+H+).

후처리

  1. customArgon was bubbled through the mixture for 5 minutes
  2. customThe flask was fitted with a reflux condenser
  3. customflushed with argon
  4. temperatureThe reaction mixture was then cooled to RT
  5. additiondiluted with a 4:1 mixture of ethyl acetate and THF
  6. extractionThe solution was extracted with 10% aqueous LiCl (2×150 mL) and brine (100 mL)
  7. dry with materialdried (MgSO4)
  8. customevaporated under reduced pressure
  9. custompurified via silica gel chromatography (ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-62bfbb0526c84f879592d882c6f033c8
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08486951B2

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