Cesium carbonate → 2-(Pyrimidin-4-yl)quinazoline-4-carboxylic acid

HRID 717345Notes

Reaction equation

HRID 717345 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=O)[C:9]([O:11]CC)=[O:10].Cl.[N:16]1[CH:21]=[CH:20][C:19]([C:22](=[NH:24])[NH2:23])=[N:18][CH:17]=1.C([O-])([O-])=O.[Cs+].[Cs+].N1CCC[C@H]1C(O)=O>CN(C)C=O.[Cu]I>[N:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:24]=[C:8]([C:9]([OH:11])=[O:10])[C:3]3[C:2](=[CH:7][CH:6]=[CH:5][CH:4]=3)[N:23]=2)=[N:18][CH:17]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 145742L-ProlineHCID 12252916Ethyl 2-(2-bromophenyl)-2-oxoacetateHCID 90411869HCID 90411869, compound

Product 1

HCID 904109312-(Pyrimidin-4-yl)quinazoline-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

Into a 250-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of ethyl 2-(2-bromophenyl)-2-oxoacetate (9 g, 35.01 mmol, 1.00 equiv) in N,N-dimethylformamide (60 mL). This was followed by the addition of pyrimidine-4-carboximidamide hydrochloride (5.53 g, 45.03 mmol, 1.29 equiv) and Cs2CO3 (11.38 g, 34.93 mmol, 1.00 equiv). The mixture was stirred for 20 min. To this was added L-proline (850 mg, 7.39 mmol, 0.21 equiv) and CuI (670 mg, 3.53 mmol, 0.10 equiv). The resulting solution was stirred for 2.5 h at 95° C. The reaction mixture was cooled to room temperature. The resulting mixture was concentrated under vacuum. The residue was dissolved in 50 mL of water. The solids were filtered out. The filtrate was washed with 2×50 mL of ethyl acetate. The pH value of the aqueous layer was adjusted to 5 with hydrogen chloride (2 mol/L). The resulting mixture was concentrated under vacuum. The crude product was purified by Flash. This resulted in 0.5 g (6%) of 2-(pyrimidin-4-yl)quinazoline-4-carboxylic acid as dark brown oil. MS (ESI) m/z 253 ([M+H]+).

Workup

  1. customInto a 250-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringThe resulting solution was stirred for 2.5 h at 95° C
  4. concentrationThe resulting mixture was concentrated under vacuum
  5. dissolutionThe residue was dissolved in 50 mL of water
  6. filtrationThe solids were filtered out
  7. washThe filtrate was washed with 2×50 mL of ethyl acetate
  8. concentrationThe resulting mixture was concentrated under vacuum
  9. customThe crude product was purified by Flash
  10. customThis resulted in 0.5 g (6%) of 2-(pyrimidin-4-yl)quinazoline-4-carboxylic acid as dark brown oil

Sources & evidence

ORD record
ord-bd7e2653fbb14fc0837db736a54d30d7
Source dataset
uspto-grants-2015_11
Patent number
US09193707B2

Reaction notes

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