Potassium Carbonate → [7-Fluoro-3-(1-methyl-1h-pyrazol-4-yl)-quinolin-6-yl]acetic acid

HRID 655254Notes

Reaction equation

HRID 655254 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([CH2:12][C:13]([OH:15])=[O:14])=[C:7]([F:16])[CH:6]=2.[CH3:17][N:18]1[CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:20]=[N:19]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:16][C:7]1[CH:6]=[C:5]2[C:10]([CH:11]=[C:2]([C:21]3[CH:20]=[N:19][N:18]([CH3:17])[CH:22]=3)[CH:3]=[N:4]2)=[CH:9][C:8]=1[CH2:12][C:13]([OH:15])=[O:14]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 59320411(3-Bromo-7-fluoro-quinolin-6-yl)-acetic acid

Product 1

HCID 59320355[7-Fluoro-3-(1-methyl-1h-pyrazol-4-yl)-quinolin-6-yl]acetic acidYield 83.1%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Nitrogen gas was bubbled through a suspension of (3-bromo-7-fluoro-quinolin-6-yl)-acetic acid (5 g, 17.7 mmol), 1-methyl-4-pyrazoleboronic acid pinacol ester (3.86 g, 18.6 mmol), potassium carbonate (7.3 g, 53 mmol) in 1,4-dioxane (50 mL) and water (20 mL) for 10 minutes. After such time dichlorobis(triphenylphosphine)palladium (II) (248 mg, 0.35 mmol) was added and the mixture heated to reflux for 3 hours. The aqueous phase was removed via pipette, diluted with 2N aqueous potassium carbonate (15 mL) and washed with ethyl acetate (2×30 mL). The aqueous phase was then acidified to pH 3 with concentrated hydrochloric acid. The formed precipitate was collected via filtration and washed with water and dried to return the title compound as a white solid (4.2 g, 14.7 mmol, 83% yield). 1H NMR 500 MHz (DMSO-d6): δ 3.84 (2H, s), 3.92 (3H, s), 7.71 (1H, d), 7.90 (1H, d), 8.10 (1H, s), 8.39 (1H, s), 8.47 (1H, d), 9.18 (1H, d). ES-MS m/z: 286 (M+H+).

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 3 hours
  3. customThe aqueous phase was removed via pipette
  4. additiondiluted with 2N aqueous potassium carbonate (15 mL)
  5. washwashed with ethyl acetate (2×30 mL)
  6. filtrationThe formed precipitate was collected via filtration
  7. washwashed with water
  8. customdried

Sources & evidence

ORD record
ord-a830ce9217ee4655a784e497997213ee
Source dataset
uspto-grants-2011_12
Patent number
US08071581B2

Reaction notes

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