Water → 3-chloro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine

HRID 450421ノート

反応式

HRID 450421 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([NH2:16])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11](Cl)[CH:10]=1.[CH3:17][N:18]1[CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:20]=[N:19]1.C([O-])([O-])=O.[K+].[K+].O>COCCOC.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>[Cl:1][C:2]1[CH:3]=[C:4]([NH2:16])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]([C:21]2[CH:20]=[N:19][N:18]([CH3:17])[CH:22]=2)[CH:10]=1

参加物

7

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 866416833-Chloro-4-(2-chloropyridin-4-yloxy)benzenamine

生成物 1

HCID 673982863-chloro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine収率 104.8%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
90 °C

実験手順

3-Chloro-4-(2-chloropyridin-4-yloxy)benzenamine (0.89 g, 3.49 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyrazole (0.871 g, 4.19 mmol) and K2CO3 (1.302 g, 9.42 mmol) were combined in DME (6 ml)/H2O (7.5 ml) and the headspace was flushed with Ar for 10 min. Pd(Ph3P)4 (0.202 g, 0.174 mmol) was then added and the biphasic reaction was stirred with heating at 90° C. overnight. The reaction was cooled to RT and filtered to remove insoluble material. The filtrate was diluted with THF and washed with brine (3×). The combined aqueous phases were extracted with THF (2×). The combined organics were washed with brine (1×), dried (MgSO4), concentrated in vacuo and purified by silica gel chromatography (MeOH/CHCl3) to afford 3-chloro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine (1.10 g, 83% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.30-8.29 (m, 1H), 8.22 (s, 1H), 7.92 (s, 1H), 7.12 (m, 1H), 7.00-6.98 (m, 1H), 6.72 (br s, 1H), 6.58-6.54 (m, 1H), 6.47-6.44 (m, 1H), 5.44 (s, 2H), 3.84 (s, 3H); MS (ESI) m/z: 301.1 (M+H+): 303.0 (M+2+H+).

後処理

  1. customthe headspace was flushed with Ar for 10 min
  2. customthe biphasic reaction
  3. temperatureThe reaction was cooled to RT
  4. filtrationfiltered
  5. customto remove insoluble material
  6. additionThe filtrate was diluted with THF
  7. washwashed with brine (3×)
  8. extractionThe combined aqueous phases were extracted with THF (2×)
  9. washThe combined organics were washed with brine (1×)
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. custompurified by silica gel chromatography (MeOH/CHCl3)

出典と根拠

ORDレコード
ord-79d174f646b84366a6088a5091e7c23c
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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