Tetrahydrofuran → 6-(4-(4-cyano-3-fluoro-2-methylphenyl)-5-methoxy-1H-pyrazol-1-yl)nicotinic acid

HRID 526583

Reaction equation

HRID 526583 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][N:10]=2)[C:6]=1[O:7][CH3:8].[F:18][C:19]1[C:26]([CH3:27])=[C:25](B2OC(C)(C)C(C)(C)O2)[CH:24]=[CH:23][C:20]=1[C:21]#[N:22].C1COCC1.C(=O)([O-])[O-].[Na+].[Na+]>CC(P(C(C)(C)C)[C]1[CH][CH][CH][CH]1)(C)C.CC(P(C(C)(C)C)[C]1[CH][CH][CH][CH]1)(C)C.Cl[Pd]Cl.[Fe].O>[C:21]([C:20]1[CH:23]=[CH:24][C:25]([C:2]2[CH:3]=[N:4][N:5]([C:9]3[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][N:10]=3)[C:6]=2[O:7][CH3:8])=[C:26]([CH3:27])[C:19]=1[F:18])#[N:22]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 1176006346-(4-bromo-5-methoxy-1H-pyrazol-1-yl)nicotinic acidHCID 1317328852-Fluoro-3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile

Product 1

HCID 1176003206-(4-(4-cyano-3-fluoro-2-methylphenyl)-5-methoxy-1H-pyrazol-1-yl)nicotinic acidYield 46.6%

Reagents, catalysts & solvents 2

HCID 178454869HCID 178454869, compoundCatalystHCID 962WaterSolvent

Procedure

Combined 6-(4-bromo-5-methoxy-1H-pyrazol-1-yl)nicotinic acid (500 mg, 1.677 mmol), 2-fluoro-3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (876 mg, 3.35 mmol), THF (10.500 mL), and water (3.50 mL) in a microwave vial. Degassed with nitrogen then added [1,1′-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (1093 mg, 1.677 mmol) and sodium carbonate (711 mg, 6.71 mmol). The reaction was degassed 2 minutes more, then capped and subjected to microwave irradiation at 110° C. for 1 hour. The reaction mixture was then diluted with EA (20 mL) and washed with water (20 mL). A precipitate was observed in the aqueous layer which was filtered and the solids collected to give 6-(4-(4-cyano-3-fluoro-2-methylphenyl)-5-methoxy-1H-pyrazol-1-yl)nicotinic acid (275 mg, 0.781 mmol, 46.5%) which was dried under vacuum and used in the next step without further purification. ESI-MS m/z [M+H]+ 353.2.

Workup

  1. customDegassed with nitrogen
  2. customThe reaction was degassed 2 minutes more
  3. customcapped
  4. customirradiation at 110° C. for 1 hour
  5. additionThe reaction mixture was then diluted with EA (20 mL)
  6. washwashed with water (20 mL)
  7. filtrationwas filtered
  8. customthe solids collected

Sources & evidence

ORD record
ord-b9b7d7bc2f3440fe84789ef3e1fb3a55
Source dataset
uspto-grants-2016_05
Patent number
US09345713B2

Linked notes

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