Cesium carbonate → HCID 66769618, 화합물

HRID 62544

반응식

HRID 62544 반응식
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

참가 물질

11

반응물 7

HCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 61695Pentapotassium TriphosphateHCID 1210181-Isopropyl-3-methyl-1H-pyrazol-5-amineHCID 4285986Bis[2-(diphenylphosphino)phenyl] ether2회HCID 99421582-Amino-4-fluorobenzonitrileHCID 534009652,5-Dichloro-4-iodopyridine

생성물 1

HCID 66769618HCID 66769618, 화합물수율 33.9%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매2회HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-20916691c74a4f9396b3128d89845b0e
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09446034B2

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