Cesium carbonate → 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-5-fluorobenzonitrile

HRID 62538ノート

反応式

HRID 62538 の反応式
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:10]=2[C:11]#[N:12])[C:5]([Cl:18])=[CH:4][N:3]=1.[CH3:19][C:20]1[CH:24]=[C:23]([NH2:25])[N:22]([CH:26]([CH3:28])[CH3:27])[N:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(OC3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=CC=3)=CC=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:18][C:5]1[C:6]([NH:8][C:9]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:10]=2[C:11]#[N:12])=[CH:7][C:2]([NH:25][C:23]2[N:22]([CH:26]([CH3:28])[CH3:27])[N:21]=[C:20]([CH3:19])[CH:24]=2)=[N:3][CH:4]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 1210181-Isopropyl-3-methyl-1H-pyrazol-5-amineHCID 4285986Bis[2-(diphenylphosphino)phenyl] etherHCID 575169182-[(2,5-Dichloro-4-pyridinyl)amino]-5-fluorobenzonitrile

生成物 1

HCID 667695842-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-5-fluorobenzonitrile収率 12.8%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

実験手順

To a solution of 2-[(2,5-dichloro-4-pyridinyl)amino]-5-fluorobenzonitrile (7.09 g, 25.1 mmol) and 3-methyl-1-(1-methylethyl)-1H-pyrazol-5-amine (3.5 g, 25.1 mmol) in 1,4-dioxane (100 mL) was added cesium carbonate (24.58 g, 75 mmol) and the reaction mixture was degassed. DPEPhos (1.083 g, 2.012 mmol) was added followed by palladium acetate (0.226 g, 1.006 mmol) and the reaction mixture was heated to reflux overnight. The suspension was then filtered. The dioxane was evaporated off. The solid was purified by flash column chromatography on silica gel (10% DCM: EtOAC). Fractions were collected and evaporated. The yellow oil was dissolved in diethyl ether, sonicated and filtered. 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-5-fluorobenzonitrile (1.3 g, 3.21 mmol, 12.76% yield) was isolated as a white solid; 1H NMR (400 MHz, METHANOL-d4) ppm 1.35 (d, J=6.82 Hz, 6 H) 2.20 (s, 3 H) 4.43 (quin, J=6.69 Hz, 1 H) 5.82 (s, 1 H) 5.89 (s, 1 H) 7.47-7.57 (m, 2 H) 7.61-7.74 (m, 1 H) 7.88 (s, 1 H); HPLC Rt=2.40 min, MS (ESI): 385.2 [M+H]+.

後処理

  1. customthe reaction mixture was degassed
  2. temperaturethe reaction mixture was heated
  3. temperatureto reflux overnight
  4. filtrationThe suspension was then filtered
  5. customThe dioxane was evaporated off
  6. customThe solid was purified by flash column chromatography on silica gel (10% DCM: EtOAC)
  7. customFractions were collected
  8. customevaporated
  9. dissolutionThe yellow oil was dissolved in diethyl ether
  10. customsonicated
  11. filtrationfiltered

出典と根拠

ORDレコード
ord-64f240f352c0435395a88f3f757f4bf2
出典データセット
uspto-grants-2016_09
特許番号
US09446034B2

反応ノート

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