Water → 4-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-amine

HRID 2060708ノート

反応式

HRID 2060708 の反応式
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:10]([CH3:16])=[CH:11][C:12]([NH2:15])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=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-].[Cs+].[Cs+].O>CN(C=O)C>[CH3:16][C:10]1[C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([C:21]3[CH:20]=[N:19][N:18]([CH3:17])[CH:22]=3)[CH:7]=2)=[CH:14][N:13]=[C:12]([NH2:15])[CH:11]=1

参加物

6

反応物 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 866416905-(2-Chloropyridin-4-yloxy)-4-methylpyridin-2-amine

生成物 1

HCID 686640964-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-amine収率 61%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

5-(2-chloropyridin-4-yloxy)-4-methylpyridin-2-amine (0.116 g, 0.492 mmol) was dissolved in DMF (2 ml) and 1-methyl-1H-pyrazole-4-boronic acid pinacol ester (0.154 g, 0.738 mmol) was added, followed by cesium carbonate (0.481 g, 1.477 mmol) and water (0.667 ml). Argon was bubbled through the mixture for several minutes, and then palladium tetrakistriphenylphosphine (0.028 g, 0.025 mmol) was added. The flask was fitted with a reflux condenser, flushed with argon, and heated under a balloon of argon at 90° C. for 16 hours. The mixture was then cooled to RT, and the solution was diluted with a 4:1 mix of ethyl acetate and THF (70 mL). It was washed with 10% aqueous LiCl (2×50 mL) and brine (50 mL), dried (MgSO4), evaporated in vacuo and purified via silica gel chromatography (DCM/MeOH) to yield 4-methyl-5-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)pyridin-2-amine as a clear oil (0.084 g, 61% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.30 (d, 1H), 8.22 (s, 1H), 7.93 (s, 1H), 7.69 (s, 1H), 7.11 (d, 1H), 6.50 (dd, 1H), 6.38 (s, 1H), 5.89 (s, 2H), 3.84 (s, 3H), 1.95 (s, 3H); MS (ESI) m/z: 282.1 (M+H+).

後処理

  1. customArgon was bubbled through the mixture for several minutes
  2. customThe flask was fitted with a reflux condenser
  3. customflushed with argon
  4. temperatureThe mixture was then cooled to RT
  5. additionthe solution was diluted with a 4:1
  6. additionmix of ethyl acetate and THF (70 mL)
  7. washIt was washed with 10% aqueous LiCl (2×50 mL) and brine (50 mL)
  8. dry with materialdried (MgSO4)
  9. customevaporated in vacuo
  10. custompurified via silica gel chromatography (DCM/MeOH)

出典と根拠

ORDレコード
ord-42fe53584d4442ed9a74053693a14b81
出典データセット
uspto-grants-2012_10
特許番号
US08278331B2

反応ノート

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