L-Glutamine → 4-carbamoyl-2-(6-methoxy-4H-quinazolin-3-yl)butanoic acid

HRID 350611Notes

Reaction equation

HRID 350611 reaction equation
[CH:1]([C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[NH:11][CH:12]=O)=O.[NH2:14][C@H:15]([C:21]([OH:23])=[O:22])[CH2:16][CH2:17][C:18](=[O:20])[NH2:19].[BH4-].[Na+]>CO.[OH-].[Na+]>[C:18]([CH2:17][CH2:16][CH:15]([N:14]1[CH2:1][C:3]2[C:4](=[CH:5][CH:6]=[C:7]([O:9][CH3:10])[CH:8]=2)[N:11]=[CH:12]1)[C:21]([OH:23])=[O:22])(=[O:20])[NH2:19]

Participants

6

Reactant 3

HCID 5961L-GlutamineHCID 4311764Sodium borohydrideHCID 21088389N-(2-formyl-4-methoxyphenyl)formamide

Product 1

HCID 210883854-carbamoyl-2-(6-methoxy-4H-quinazolin-3-yl)butanoic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 14798Sodium HydroxideSolvent2×

Conditions

Temperature
20 °C

Procedure

A solution of 0.79 g of the product from stage 3 in 30 ml of methanol was added to a solution of 0.58 g of L-glutamine in 10 ml of methanol and 2 ml of 2N sodium hydroxide solution. After stirring for 1 hour at 20° C., the mixture was cooled to 0° C. and 0.103 g of sodium borohydride was added in portions within 30 minutes. The mixture was stirred for 12 hours at 0° C., then adjusted to pH 2 to 3, and stirred for a further 4 hours at 20° C. After neutralizing the solution with sodium hydroxide, the methanol was distilled off. The aqueous residue was washed twice with 15 ml of diethyl ether each time, and then concentrated by evaporation in vacuo. The residue was taken up in 25 ml of methanol and freed from insoluble constituents by filtration. The residue obtained by evaporating the filtrate in vacuo was directly reacted further as described in stage 5, without purification.

Workup

  1. temperaturethe mixture was cooled to 0° C.
  2. stirringThe mixture was stirred for 12 hours at 0° C.
  3. stirringstirred for a further 4 hours at 20° C
  4. distillationthe methanol was distilled off
  5. washThe aqueous residue was washed twice with 15 ml of diethyl ether each time
  6. concentrationconcentrated by evaporation in vacuo
  7. filtrationfreed from insoluble constituents by filtration
  8. customThe residue obtained
  9. customby evaporating the filtrate in vacuo
  10. customas described in stage 5, without purification

Sources & evidence

ORD record
ord-be8db5e7db014e8587df42f2c21fd59c
Source dataset
uspto-grants-2007_02
Patent number
US07183274B2

Reaction notes

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