Acetic Acid → 4-fluoro-3-(7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamido)benzoic acid

HRID 335275

Reaktionsgleichung

Reaktionsgleichung von HRID 335275
C[O:2][C:3](=[O:24])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[C:6]([NH:11][C:12]([C:14]2[N:18]3[CH:19]=[CH:20][C:21](Br)=[CH:22][C:17]3=[N:16][CH:15]=2)=[O:13])[CH:5]=1.[CH3:25][N:26]1[CH:30]=[CH:29][C:28](B2OC(C)(C)C(C)(C)O2)=[N:27]1.C(Cl)Cl.CC(O)=O>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:10][C:7]1[CH:8]=[CH:9][C:4]([C:3]([OH:2])=[O:24])=[CH:5][C:6]=1[NH:11][C:12]([C:14]1[N:18]2[CH:19]=[CH:20][C:21]([C:30]3[N:26]([CH3:25])[N:27]=[CH:28][CH:29]=3)=[CH:22][C:17]2=[N:16][CH:15]=1)=[O:13]

Komponenten

8

Edukt 4

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 27600771-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 712828883-[(7-Bromo-imidazo[1,2-a]pyridine-3-carbonyl)-amino]-4-fluoro-benzoic Acid Methyl Ester

Produkt 1

HCID 712829094-fluoro-3-(7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamido)benzoic acid

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 10340Sodium CarbonateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

3-[(7-Bromo-imidazo[1,2-a]pyridine-3-carbonyl)-amino]-4-fluoro-benzoic acid methyl ester (step 1) (1200 g, 3.060 mol), 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (commercially available) (764 g, 3.67 mol), PdCl2(dppf).CH2Cl2 (75.0 g, 91.8 mmol) in dioxane (10 L) and aqueous Na2CO3 (2 N, 4.6 L) were heated to reflux for 6 hr. The reaction mixture was cooled to 50° C. and filtered. The filtrate was heated to reflux, to which was added AcOH (600 g, 10.0 mol) was added dropwise. During the course of addition solids came out of solution to give pale pink slurry. After addition the mixture was slowly cooled to RT and filtered. To the filter cake was added dioxane (20 L) followed by heating to reflux to obtain a solution. The solution was cooled to RT and filtered to provide the title compound as a white solid;

Aufarbeitung

  1. temperatureto reflux for 6 hr
  2. filtrationfiltered
  3. temperatureThe filtrate was heated
  4. temperatureto reflux, to which
  5. additionwas added dropwise
  6. additionDuring the course of addition solids
  7. customto give pale pink slurry
  8. additionAfter addition the mixture
  9. temperaturewas slowly cooled to RT
  10. filtrationfiltered
  11. additionTo the filter cake was added dioxane (20 L)
  12. temperatureby heating
  13. temperatureto reflux
  14. customto obtain a solution
  15. temperatureThe solution was cooled to RT
  16. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-a2ea1f2e0b6c42bb87c8b8b87ece3f33
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08883819B2

Verknüpfte Notizen

Wird geladen…