Cesium carbonate → 2-[[5-Chloro-2-[(1-ethyl-3-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl]amino]-N-ethylbenzamide

HRID 62497ノート

反応式

HRID 62497 の反応式
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([NH:13][CH2:14][CH3:15])=[O:12])[C:5]([Cl:20])=[CH:4][N:3]=1.[CH2:21]([N:23]1[C:27]([NH2:28])=[CH:26][C:25]([CH3:29])=[N:24]1)[CH3:22].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1.C1COCC1>[Cl:20][C:5]1[C:6]([NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([NH:13][CH2:14][CH3:15])=[O:12])=[CH:7][C:2]([NH:28][C:27]2[N:23]([CH2:21][CH3:22])[N:24]=[C:25]([CH3:29])[CH:26]=2)=[N:3][CH:4]=1

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 27683831-Ethyl-3-methyl-1H-pyrazol-5-amineHCID 57516899HCID 57516899、化合物

生成物 1

HCID 462149312-[[5-Chloro-2-[(1-ethyl-3-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl]amino]-N-ethylbenzamide収率 35%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 8028Tetrahydrofuran溶媒HCID 312751,4-Dioxane溶媒2 回

反応条件

温度
160 °C

実験手順

A vessel was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]-N-ethylbenzamide (100 mg, 0.322 mmol), 1-ethyl-3-methyl-1H-pyrazol-5-amine (60.5 mg, 0.484 mmol), cesium carbonate (315 mg, 0.967 mmol), 1,4-dioxane (5.0 mL), and THF (1.0 mL). The reaction mixture was degassed by nitrogen for 10 min at which time (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (40.1 mg, 0.064 mmol) and palladium (II) acetate (7.24 mg, 0.032 mmol) in a minimum amount of 1,4-dioxane were added. The vessel was sealed and the reaction mixture was heated in microwave oven 160° C. for 40 min. The resulting suspension was cooled to room temperature and filtered through celite. The filtrate was evaporated to dryness and the crude reaction mixture was purified by reverse-phase HPLC to give the title compound as a solid (45 mg, 30% yield); MS: M(C20H23ClN6O)=398.89, (M+H)+=399, 401; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.34 (s, 1 H) 7.94 (s, 1 H) 7.66 (br. s., 1 H) 7.51 (d, J=7.8 Hz, 1 H) 7.31-7.47 (m, 2 H) 6.96-7.17 (m, 1 H) 6.58 (s, 1 H) 6.19 (t, J=5.2 Hz, 1 H) 5.86 (s, 1 H) 4.01 (q, J=7.3 Hz, 2 H) 3.42-3.62 (m, 2 H) 2.24 (s, 3 H) 1.37 (t, J=7.3 Hz, 3 H) 1.26 (t, J=7.3 Hz, 3 H).

後処理

  1. additionwere added
  2. customThe vessel was sealed
  3. temperatureThe resulting suspension was cooled to room temperature
  4. filtrationfiltered through celite
  5. customThe filtrate was evaporated to dryness
  6. customthe crude reaction mixture
  7. customwas purified by reverse-phase HPLC

出典と根拠

ORDレコード
ord-e8469549f1b344bdbe99b0e4bac15810
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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