Ethyl Acetate → 1-[4-(3-amino-1H-pyrazolo[4,3-c]pyrid-4-yl)phenyl]-3-(2-fluoro-5-trifluoromethylphenyl)urea

HRID 1677636Notes

Reaction equation

HRID 1677636 reaction equation
Br[C:2]1[C:7]2[C:8]([NH2:11])=[N:9][NH:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=1[NH:23][C:24]([NH:26][C:27]1[CH:32]=[CH:31][C:30](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH:28]=1)=[O:25].C(=O)(O)[O-].[Na+].C(OCC)(=O)C>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:11][C:8]1[C:7]2[C:2]([C:30]3[CH:29]=[CH:28][C:27]([NH:26][C:24]([NH:23][C:14]4[CH:15]=[C:16]([C:19]([F:20])([F:22])[F:21])[CH:17]=[CH:18][C:13]=4[F:12])=[O:25])=[CH:32][CH:31]=3)=[N:3][CH:4]=[CH:5][C:6]=2[NH:10][N:9]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 161252301-(2-Fluoro-5-(trifluoromethyl)phenyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureaHCID 583807624-bromo-1H-pyrazolo[4,3-c]pyridin-3-amine

Product 1

HCID 116333621-[4-(3-amino-1H-pyrazolo[4,3-c]pyrid-4-yl)phenyl]-3-(2-fluoro-5-trifluoromethylphenyl)ureaYield 31.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 178418397HCID 178418397, compoundSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 53 mg of 4-bromo-1H-pyrazolo[4,3-c]pyrid-3-ylamine in 6 mL of dioxane are added 127 mg of 1-(2-fluoro-5-trifluoromethylphenyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea, 60 mg of sodium bicarbonate in 1.8 mL of water and 30 mg of tetrakis(triphenylphosphine)palladium. The reaction is heated in a bath at 100° C. for 2 hours. The mixture is allowed to cool and ethyl acetate is then added. The mixture is washed with water. The organic phase is dried over magnesium sulfate and then concentrated under reduced pressure. The oily residue is purified on a prepacked Biotage KP-Sil column of 60 Å SiO2 32-63 μm (gradient: 90/10 to 70/30 dichloromethane/solution A; solution A=38/17/2 dichloromethane/methanol/aqueous ammonia). 34 mg of 1-[4-(3-amino-1H-pyrazolo[4,3-c]pyrid-4-yl)phenyl]-3-(2-fluoro-5-trifluoromethylphenyl)urea are obtained in the form of a cream-coloured solid, the characteristics of which are as follows:

Workup

  1. temperatureto cool
  2. washThe mixture is washed with water
  3. dry with materialThe organic phase is dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe oily residue is purified on a prepacked Biotage KP-Sil column of 60 Å SiO2 32-63 μm (gradient: 90/10 to 70/30 dichloromethane/solution A; solution A=38/17/2 dichloromethane/methanol/aqueous ammonia)

Sources & evidence

ORD record
ord-f1c9b8d387eb481cb5258ba9afc5a3ba
Source dataset
uspto-grants-2011_08
Patent number
US08008322B2

Reaction notes

Loading…