Sodium Acetate → Methyl 3-(methylthio)-5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate

HRID 1919631Notes

Reaction equation

HRID 1919631 reaction equation
Br[C:2]1[C:3]([C:10]([O:12]C)=O)=[N:4][C:5]([S:8][CH3:9])=[N:6][CH:7]=1.Cl.[NH2:15][C:16]1[CH:21]=[C:20]([C:22]([O:24][CH3:25])=[O:23])[CH:19]=[CH:18][C:17]=1B(O)O.C([O-])(=O)C.[Na+]>CN(C=O)C>[CH3:9][S:8][C:5]1[N:6]=[CH:7][C:2]2[C:17]3[CH:18]=[CH:19][C:20]([C:22]([O:24][CH3:25])=[O:23])=[CH:21][C:16]=3[NH:15][C:10](=[O:12])[C:3]=2[N:4]=1

Participants

5

Reactant 3

HCID 517045Sodium AcetateHCID 2794729Methyl 5-bromo-2-(methylsulfanyl)pyrimidine-4-carboxylateHCID 16427083[2-Amino-4-(methoxycarbonyl)phenyl]boronic acid--hydrogen chloride (1/1)

Product 1

HCID 57500644Methyl 3-(methylthio)-5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylateYield 79.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

In a microwave vessel, methyl 5-bromo-2-(methylthio)pyrimidine-4-carboxylate (1.0 eq, 274 mg, 1.18 mmol), 2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride (1.2 eq, 329 mg, 1.42 mmol), and sodium acetate (3.0 eq, 291 mg, 3.55 mmol) were mixed in anhydrous DMF (2 ml). The mixture was degassed by bubbling nitrogen gas in the solution for 10 min and the reaction heated under microwaves at 120° C. for 30 min. After cooling down the expected material crashed out of NMP. The solid was filtered, suspended in water filtered and dried. The material was triturated in AcOEt and filtered give a yellow solid. The same procedure was repeated 9 times using the same amounts of materials to provide methyl 3-(methylthio)-5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate (283 mg, 10% yield). LCMS (ES): >95% pure, m/z 302 [M+1]+, 1H NMR (DMSO-d6, 400 MHz) δ 2.71 (s, 3H), 3.89 (s, 3H), 7.80 (dd, J=1.6, J=8.4, 1H), 7.97 (d, J=1.6, 1H), 8.59 (d, J=8.8, 1H), 9.98 (s, 1H), 12.34 (s, 1H) ppm.

Workup

  1. customThe mixture was degassed
  2. customby bubbling nitrogen gas in the solution for 10 min
  3. temperatureAfter cooling down the expected material
  4. filtrationThe solid was filtered
  5. filtrationfiltered
  6. customdried
  7. customThe material was triturated in AcOEt
  8. filtrationfiltered
  9. customgive a yellow solid

Sources & evidence

ORD record
ord-1b5ec41c869e41bc9ea160105ace175e
Source dataset
uspto-grants-2012_05
Patent number
US08168651B2

Reaction notes

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