Dichloromethane → 3-Amino-6-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)picolinic acid

HRID 444913Notes

Reaction equation

HRID 444913 reaction equation
C[O:2][C:3]([C:5]1[C:10]([NH2:11])=[CH:9][C:8]([C:12]([F:15])([F:14])[F:13])=[C:7](Br)[N:6]=1)=[O:4].C(Cl)Cl.[CH3:20][N:21]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[N:22]1.C([O-])([O-])=O.[Cs+].[Cs+].[OH-].[Na+]>C1COCC1.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]>[NH2:11][C:10]1[C:5]([C:3]([OH:2])=[O:4])=[N:6][C:7]([C:24]2[CH:23]=[N:22][N:21]([CH3:20])[CH:25]=2)=[C:8]([C:12]([F:15])([F:14])[F:13])[CH:9]=1

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 58964428Methyl 3-amino-6-bromo-5-(trifluoromethyl)picolinate2×

Product 1

HCID 673832773-Amino-6-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)picolinic acid

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

3-Amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester (Intermediate A4) (500 mg, 1.672 mmol), PdCl2(dppf).CH2Cl2 adduct (205 mg, 0.251 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (383 mg, 1.839 mmol) and Cs2CO3 (6.69 ml, 6.69 mmol) in THF (12 ml) under N2, was heated using microwave radiation at 150° C. for 10 minutes. 2M NaOH (5 ml) was added and the mixture was stirred at RT overnight. The mixture was filtered through Celite® (filter material) and the organic solvent was removed. The resulting aqueous layer was washed with EtOAc and acidified to pH1. The product was extracted with DCM and concentrated in vacuo to afford the title compound;

Workup

  1. customat 150° C.
  2. customfor 10 minutes
  3. filtrationThe mixture was filtered through Celite® (filter material)
  4. customthe organic solvent was removed
  5. washThe resulting aqueous layer was washed with EtOAc
  6. extractionThe product was extracted with DCM
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f8082be76d3843d5b5ac68b5abba30ad
Source dataset
uspto-grants-2013_07
Patent number
US08476269B2

Reaction notes

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