Hydrochloric Acid → Methyl 4-(4-amino-6-methoxyquinolin-2-yl)benzoate

HRID 1410604Notes

Reaction equation

HRID 1410604 reaction equation
ClC1C=C(C=CC=1[C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16](O)[CH:17]=2)[N:12]=1)C(O)=O.[CH3:22][O:23][C:24]([C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1)=[O:25].[C:35]([O-:38])([O-])=O.[K+].[K+].Cl.C[N:43](C=O)C>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:43][C:19]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([O:38][CH3:35])[CH:17]=2)[N:12]=[C:11]([C:29]2[CH:30]=[CH:31][C:26]([C:24]([O:23][CH3:22])=[O:25])=[CH:27][CH:28]=2)[CH:20]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 27343694-Methoxycarbonylphenylboronic acidHCID 56960912Cavosonstat

Product 1

HCID 66980112Methyl 4-(4-amino-6-methoxyquinolin-2-yl)benzoateYield 46%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Procedure

A mixture solution of Intermediate 8 (4.70 g, 22.5 mmol), 4-methoxycarbonylphenylboronic acid (4.01 g, 22.5 mmol), K2CO3 (6.53 g, 47.2 mmol), Pd(dppf)Cl2 (470 mg, 0.407 mmol) in DMF (20 mL) and H2O (4 mL) was stirred under N2 atmosphere at 130° C. for 5 hours. The mixture was cooled, acidified with aqueous HCl (1M) until pH=6 and extracted with EtOAc (80 mL×3). The combined organic layers were washed with brine (150 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was washed with EtOAc (50 mL), the mixture was filtered then concentrated to give the product (3.20 g, yield 46%) as an off-white solid.

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted with EtOAc (80 mL×3)
  3. washThe combined organic layers were washed with brine (150 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. washThe residue was washed with EtOAc (50 mL)
  7. filtrationthe mixture was filtered
  8. concentrationthen concentrated

Sources & evidence

ORD record
ord-512ec1d416b84f3da3f37972ab35bd0d
Source dataset
uspto-grants-2014_12
Patent number
US08921562B2

Reaction notes

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