Water → Methyl 5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate

HRID 604354Notes

Reaction equation

HRID 604354 reaction equation
C([O-])(=O)C.[Na+].CO[C:8]([C:10]1[C:15](Br)=[CH:14][N:13]=[CH:12][N:11]=1)=[O:9].Cl.[NH2:18][C:19]1[CH:24]=[C:23]([C:25]([O:27][CH3:28])=[O:26])[CH:22]=[CH:21][C:20]=1B(O)O.O>CN(C=O)C.[Cl-].[Na+].O.[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]>[O:9]=[C:8]1[C:10]2[N:11]=[CH:12][N:13]=[CH:14][C:15]=2[C:20]2[CH:21]=[CH:22][C:23]([C:25]([O:27][CH3:28])=[O:26])=[CH:24][C:19]=2[NH:18]1

Participants

8

Reactant 4

HCID 962WaterHCID 517045Sodium AcetateHCID 164270832-Amino-4-(methoxycarbonyl)benzeneboronic acid hydrochlorideHCID 45790077Methyl 5-bromopyrimidine-4-carboxylate

Product 1

HCID 50942144Methyl 5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylateYield 8.5%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
120 °C

Procedure

Sodium acetate (4.0 eq, 1.92 g, 23.41 mmol) and 1,1′-bis(diphenylphosphino)ferrocene palladium (II) chloride (complexed with dichloromethane) (0.05 eq, 214 mg, 0.29 mmol) were added to a mixture of methyl-5-bromopyrimidine-4-carboxylate (1.0 eq, 1.27 g, 5.85 mmol), and 2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride (1.0 eq, 1.35 g, 5.85 mmol) in anhydrous DMF (10 ml). The mixture was stirred under nitrogen atmosphere at 120° C. for 18 hours. Water and brine were added and the resulting solid impurities filtered off. The material was extracted with CH2Cl2 (4×) and the combined extracts dried over Na2SO4. After evaporation of CH2Cl2, the remaining DMF was evaporated by heating the residue in vacuo. The resulting solid was triturated in CH2Cl2, filtered and dried to provide methyl 5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate as a beige solid (127 mg, 8.5% yield). LCMS (ES): >80% pure, m/z 256 [M+1]+; 1H NMR (DMSO-d6, 400 MHz) δ 3.79 (s, 3H), 7.81 (d, J=8.0, 1H), 8.68 (d, J=8.8, 1H), 9.49 (s, 1H), 10.19 (s, 1H), 12.37 (s, 1H) ppm.

Workup

  1. filtrationthe resulting solid impurities filtered off
  2. extractionThe material was extracted with CH2Cl2 (4×)
  3. dry with materialthe combined extracts dried over Na2SO4
  4. customAfter evaporation of CH2Cl2
  5. customthe remaining DMF was evaporated
  6. temperatureby heating the residue in vacuo
  7. customThe resulting solid was triturated in CH2Cl2
  8. filtrationfiltered
  9. customdried

Sources & evidence

ORD record
ord-77b27c98ad24481285d9333c1344243d
Source dataset
uspto-grants-2011_03
Patent number
US07910600B2

Reaction notes

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