Cesium carbonate → HCID 66769618、化合物

HRID 62544

反応式

HRID 62544 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[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:12]=1C#N.[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:87](=[O:90])([O-])[O-:88].[Cs+].[Cs+].[OH-].[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C>[Cl:9][C:5]1[C:6]([NH:10][C:11]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:12]=2[C:87]([OH:88])=[O:90])=[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

11

反応物 7

HCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 61695Pentapotassium TriphosphateHCID 1210181-Isopropyl-3-methyl-1H-pyrazol-5-amineHCID 4285986Bis[2-(diphenylphosphino)phenyl] ether2 回HCID 99421582-Amino-4-fluorobenzonitrileHCID 534009652,5-Dichloro-4-iodopyridine

生成物 1

HCID 66769618HCID 66769618、化合物収率 33.9%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒2 回HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

To a degassed solution of 2,5-dichloro-4-iodopyridine (5 g, 18.26 mmol), 2-amino-4-fluorobenzonitrile (2.485 g, 18.26 mmol) and potassium triphosphate (11.63 g, 54.8 mmol) in 1,4-dioxane (60 ml) stirred under nitrogen at the room temperature was added DPEPhos (0.787 g, 1.460 mmol) and palladium acetate (0.164 g, 0.730 mmol). The reaction mixture was stirred at the reflux for 18 hr. The reaction mixture was filtered. 3-Methyl-1-(1-methylethyl)-1H-pyrazol-5-amine (2.54 g, 18.26 mmol) and cesium carbonate (17.84 g, 54.8 mmol) were added. The reaction mixture was degassed and palladium acetate (0.164 g, 0.730 mmol) and DPEPhos (0.787 g, 1.460 mmol) were added. The reaction mixture was refluxed overnight. The reaction mixture was filtered. NaOH (60 mL, 60.0 mmol) was added and the reaction mixture refluxed overnight. Ethyl acetate was added and the layers were separated. The combined organics were washed with 1 M NaOH (40 ml). The combined aqueous layers were washed with ethyl acetate, and neutralized with acetic acid. 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-4-fluorobenzoic acid (2.5 g, 6.19 mmol, 33.9% yield) was isolated by filtration as a yellow solid. 1H NMR (400 MHz, DMSO-d6) ppm 1.29 (d, J=6.57 Hz, 6 H) 2.12 (s, 3 H) 4.43 (quin, J=6.57 Hz, 1 H) 5.99 (s, 1 H) 6.86 (s, 1 H) 6.87-6.93 (m, 1 H) 7.34 (dd, J=11.62, 2.53 Hz, 1 H) 8.03-8.10 (m, 2 H) 8.62 (s, 1 H) 10.65 (br. s., 1 H); HPLC Rt=2.57 min, MS (ESI): 404.2 [M+H]+.

後処理

  1. temperaturereflux 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. temperaturethe reaction mixture refluxed overnight
  7. customthe layers were separated
  8. washThe combined organics were washed with 1 M NaOH (40 ml)
  9. washThe combined aqueous layers were washed with ethyl acetate

出典と根拠

ORDレコード
ord-20916691c74a4f9396b3128d89845b0e
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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