Methyl 6-chloropyridine-3-carboxylate → HCID 21914626, compound

HRID 2108963Notes

Reaction equation

HRID 2108963 reaction equation
[CH:1]1([NH:4][C:5](=[O:23])[C:6]2[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[C:8](B3OC(C)(C)C(C)(C)O3)[CH:7]=2)[CH2:3][CH2:2]1.Cl[C:25]1[CH:34]=[CH:33][C:28]([C:29]([O:31]C)=[O:30])=[CH:27][N:26]=1.C(=O)([O-])O.[Na+]>CC(O)C.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>[CH:1]1([NH:4][C:5]([C:6]2[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[C:8]([C:25]3[CH:34]=[CH:33][C:28]([C:29]([OH:31])=[O:30])=[CH:27][N:26]=3)[CH:7]=2)=[O:23])[CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 516892Sodium BicarbonateHCID 21914563N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide

Product 1

HCID 21914626HCID 21914626, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

N-Cyclopropyl-5-fluoro-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (3.2 g), methyl 6-chloronicotinate (1.73 g), tetrakis(triphenylphosphine)palladium (210 mg) and aqueous sodium hydrogen carbonate (1M, 30 ml) were mixed in propan-2-ol (100 ml) and heated at 90° C. for 18 hours. The reaction was allowed to cool and the propan-2-ol removed under vacuum. The residue was partitioned between ethyl acetate and aqueous sodiumhydrogen carbonate (1M). The aqueous phase was acidified with hydrochloric acid (2N) and extracted with ethyl acetate (x2). The organic extracts were washed with brine, dried (magnesium sulphate) and reduced to dryness under vacuum. The resulting foam was triturated with ether to give 6-{5-[(cyclopropylamino)carbonyl]-3-fluoro-2-methylphenyl}nicotinic acid as a solid.

Workup

  1. temperatureto cool
  2. customthe propan-2-ol removed under vacuum
  3. customThe residue was partitioned between ethyl acetate and aqueous sodiumhydrogen carbonate (1M)
  4. extractionextracted with ethyl acetate (x2)
  5. washThe organic extracts were washed with brine
  6. dry with materialdried (magnesium sulphate)
  7. customThe resulting foam was triturated with ether

Sources & evidence

ORD record
ord-9991c21c3d954552a72a99846007bfd9
Source dataset
uspto-grants-2009_04
Patent number
US07514456B2

Reaction notes

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