Water → HCID 178524221, compound

HRID 927361Notes

Reaction equation

HRID 927361 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:13]([OH:15])=[O:14])=[N:6][C:7]=1[O:8][CH2:9][CH:10]1[CH2:12][CH2:11]1.[NH:16]1[CH:20]=[CH:19][C:18](B(O)O)=[N:17]1.C(=O)([O-])[O-].[Na+].[Na+].O>CN(C=O)C.C(Cl)Cl.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH:10]1([CH2:9][O:8][C:7]2[N:6]=[C:5]([C:13]([OH:15])=[O:14])[CH:4]=[CH:3][C:2]=2[C:20]2[CH:19]=[CH:18][NH:17][N:16]=2)[CH2:12][CH2:11]1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 710875435-Bromo-6-cyclopropylmethoxy-pyridine-2-carboxylic acidHCID 178514837HCID 178514837, compound

Product 1

HCID 178524221HCID 178524221, compoundYield 66.7%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

Under an atmosphere of nitrogen, a solution of 5-bromo-6-(cyclopropylmethoxy)-pyridine-2-carboxylic acid (Example 9 d, 0.4 g, 1.5 mmol), 1H-pyrazol-3-ylboronic acid (CAN 376584-63-3, 0.2 g, 1.8 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride methylene chloride complex (CAN 95464-05-4, 60 mg, 0.07 mmol) and sodium carbonate (1.3 g, 12 mmol) in DMF (10 mL) was heated to 100° C. for 5 h. The reaction mixture was poured into water and extracted with ethyl acetate (30 mL). The aqueous layer was adjusted to pH=2 by addition of 1 N hydrochloric acid and the resulting mixture was extracted with ethyl acetate (3×30 mL). The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate and evaporated. The residue was purified by column chromatography (silica gel, 15 g, eluting with 30% ethyl acetate in petroleum ether) to yield the title compound (0.23 g, 1 mmol, 60.3%) as white solid; MS (EI): m/e 260.1 [M+H]+.

Workup

  1. customwas heated to 100° C. for 5 h
  2. extractionextracted with ethyl acetate (30 mL)
  3. additionThe aqueous layer was adjusted to pH=2 by addition of 1 N hydrochloric acid
  4. extractionthe resulting mixture was extracted with ethyl acetate (3×30 mL)
  5. washThe combined organic extracts were washed with water and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated
  8. customThe residue was purified by column chromatography (silica gel, 15 g, eluting with 30% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-f95c0132d282452b8245fb3c241d99de
Source dataset
uspto-grants-2016_03
Patent number
US09290451B2

Reaction notes

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