Sodium Carbonate → 6-(4-Carboxyphenyl)-8-methoxy-1,7-naphthyridine

HRID 369035

Reaction equation

HRID 369035 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C:14](=[C:15]([O:17][CH3:18])[N:16]=1)[N:13]=[CH:12][CH:11]=[CH:10]2)(=O)=O.[C:21]([C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1)([OH:23])=[O:22].C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>[C:21]([C:24]1[CH:29]=[CH:28][C:27]([C:7]2[CH:8]=[C:9]3[C:14](=[C:15]([O:17][CH3:18])[N:16]=2)[N:13]=[CH:12][CH:11]=[CH:10]3)=[CH:26][CH:25]=1)([OH:23])=[O:22]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 3121834-Carboxyphenylboronic AcidHCID 232846356-Trifluoromethylsulfonyloxy-8-methoxy-1,7-naphthyridine

Product 1

HCID 232846426-(4-Carboxyphenyl)-8-methoxy-1,7-naphthyridineYield 80.8%

Reagents, catalysts & solvents 3

HCID 80271Tri-o-tolylphosphineCatalystHCID 1542701,5-Diphenylpenta-1,4-dien-3-one;palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-trifluoromethylsulfonyloxy-8-methoxy-1,7-napthyridine (1.5 g, 4.86 mmol) in DMF (40 ml) is added 4-carboxy-phenylboronic acid (0.866 g, 5.34 mmol), bis(dibenzylidenacetone) palladium (112 mg, 0.167 mmol), tri-o-tolylphosphine (96 mg, 0.32 mmol) and aqueous Na2CO3 (14.6 ml, 2N,). The reaction mixture is stirred at 110° for 3 h. The hot solution is filtred through cellit and the solution evaporated to dryness. The crude product is dissolved in hot water (60 ml) and the water phase washed with ethyl acetate (3×50 ml). The product is precipitated from the water phase by carefully adding aqueous HCl (2N, 6 ml). The suspension is filtered and the crude product is stirred again in hot ethyl acetate (50 ml). The cold suspension is filtered to yield the title compound (1.10 g). M+280; Melting point >300°.

Workup

  1. customthe solution evaporated to dryness
  2. dissolutionThe crude product is dissolved in hot water (60 ml)
  3. washthe water phase washed with ethyl acetate (3×50 ml)
  4. customThe product is precipitated from the water phase by carefully adding aqueous HCl (2N, 6 ml)
  5. filtrationThe suspension is filtered
  6. stirringthe crude product is stirred again in hot ethyl acetate (50 ml)
  7. filtrationThe cold suspension is filtered

Sources & evidence

ORD record
ord-449fc1ba55304cbb90163e63a52ba620
Source dataset
uspto-grants-2000_10
Patent number
US06136821

Linked notes

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