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

HRID 62541

反応式

HRID 62541 の反応式
Cl[C:2]1[CH:7]=[C:6](I)[C:5]([Cl:9])=[CH:4][N:3]=1.[NH2:10][C:11]1[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:12]=1[C:13]#[N:14].[O-]P(OP(OP([O-])([O-])=O)([O-])=O)(=O)[O-].[K+].[K+].[K+].[K+].[K+].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.[CH3:77][C:78]1[CH:82]=[C:81]([NH2:83])[N:80]([CH:84]([CH3:86])[CH3:85])[N:79]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:9][C:5]1[C:6]([NH:10][C:11]2[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:12]=2[C:13]#[N:14])=[CH:7][C:2]([NH:83][C:81]2[N:80]([CH:84]([CH3:86])[CH3:85])[N:79]=[C:78]([CH3:77])[CH:82]=2)=[N:3][CH:4]=1

参加物

9

反応物 6

HCID 10796Cesium carbonateHCID 61695Pentapotassium TriphosphateHCID 1210181-Isopropyl-3-methyl-1H-pyrazol-5-amineHCID 27833922-Amino-3-fluorobenzonitrileHCID 4285986Bis[2-(diphenylphosphino)phenyl] ether2 回HCID 534009652,5-Dichloro-4-iodopyridine

生成物 1

HCID 667697122-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-3-fluorobenzonitrile収率 53.4%

試薬・触媒・溶媒 2

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

反応条件

温度
50 °C

実験手順

To a degassed solution of 2,5-dichloro-4-iodopyridine (8 g, 29.2 mmol), 2-amino-3-fluorobenzonitrile (3.98 g, 29.2 mmol) and potassium triphosphate (18.60 g, 88 mmol) in 1,4-dioxane (60 ml) stirred under nitrogen at the room temperature was added DPEPhos (1.258 g, 2.337 mmol) and palladium acetate (0.262 g, 1.168 mmol) The reaction mixture was stirred at reflux for 18 hr. The reaction mixture was filtered. 3-Methyl-1-(1-methylethyl)-1H-pyrazol-5-amine (4.07 g, 29.2 mmol) and cesium carbonate (28.6 g, 88 mmol) were added. The reaction mixture was degassed and palladium acetate (0.262 g, 1.168 mmol) and DPEPhos (1.258 g, 2.337 mmol) were added. The reaction mixture was refluxed overnight. The reaction mixture was filtered and the solid was dissolved in water, heated to 50° C. and stirred for 10 minutes, then filtered again. 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-3-fluorobenzonitrile (6 g, 15.59 mmol, 53.4% yield) was isolated as an orange solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.23 (d, J=6.57 Hz, 6 H) 2.07 (s, 3 H) 4.32 (quin, J=6.57 Hz, 1 H) 5.64 (d, J=2.02 Hz, 1 H) 5.83 (s, 1 H) 7.39-7.58 (m, 1 H) 7.63-7.82 (m, 2 H) 7.88 (s, 1 H) 8.26 (br. s., 1 H) 8.41 (br. s., 1 H); HPLC Rt=2.35 min, MS (ESI): 385.0 [M+H]+.

後処理

  1. temperatureat reflux for 18 hr
  2. filtrationThe reaction mixture was filtered
  3. customThe reaction mixture was degassed
  4. temperatureThe reaction mixture was refluxed overnight
  5. filtrationThe reaction mixture was filtered
  6. dissolutionthe solid was dissolved in water
  7. stirringstirred for 10 minutes
  8. filtrationfiltered again

出典と根拠

ORDレコード
ord-6e3639a55755478ca870328a0ec3630d
出典データセット
uspto-grants-2016_09
特許番号
US09446034B2

関連ノート

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