Water → HCID 136151023, compound

HRID 1590052Notes

Reaction equation

HRID 1590052 reaction equation
[CH3:1][CH2:2][N:3]([CH2:6][CH3:7])[CH2:4][CH3:5].[C:8](Cl)(=O)[CH2:9][CH2:10][CH2:11][CH3:12].[C:15](=[O:18])([O-])[O-].[NH4+:19].[NH4+:20].[OH2:21]>CN(C=O)C.CN(C1C=CN=CC=1)C>[CH2:9]([C:8]1[NH:20][C:15](=[O:18])[C:10]2[C:9](=[CH:8][CH:1]=[C:2]([N:3]3[CH2:6][CH2:7][O:21][CH2:5][CH2:4]3)[CH:11]=2)[N:19]=1)[CH2:10][CH2:11][CH3:12]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 61186Valeryl chlorideHCID 517111Ammonium Carbonate

Product 1

HCID 136151023HCID 136151023, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

The acid (1.57 g, 5.11 mmol) was dissolved in 80 mL DMF to which was added 2.1 mL (15.3 mmol) Et3N, about 50 mg DMAP, and 0.728 mL (6.13 mmol) valeryl chloride. After 10 minutes the mixture was heated to 110° C. After 1 hour, 3.8 g (30.7 mmol) ammonium carbonate was added over about 8 minutes (CAUTION: Frothing occurs and could cause boilover). After 30 minutes the mixture was cooled to room temperature and poured into water. The precipitate was collected on filtration through a medium fritted funnel. The solid was redissolved in methanol to which was added 2 mL 50% NaOH. The mixture was heated to reflux for 30 minutes to complete the conversion of the bis-amide to quinazolinone. The mixture was cooled to room temperature, phenolphthalein was added and the mixture was acidified with concentrated HCl until colorless. Water was added and the precipitated solid was collected. The mother liquor was heated again and a second crop of crystals was taken to give a combined total of 958 mg of product in 65% yield. Rf 0.25 in 40% EtOAc/hexane, visualized by UV and ammonium molybdate/ceric sulfate stain; 1H-NMR (400 MHz, DMSO-d6): δ 11.99 (br s, 1H), 7.50 (m, 2H), 7.38 (m, 1H), 3.76 (3 line m, 4H), 3.18 (3 line m, 4H), 2.55 (3 line m, 2H), 1.68 (5 line m, 2H), 1.33 (6 line m, 2H), 0.90 (3 line m, 3H).

Workup

  1. temperatureAfter 30 minutes the mixture was cooled to room temperature
  2. filtrationThe precipitate was collected on filtration through a medium fritted funnel
  3. dissolutionThe solid was redissolved in methanol to which
  4. additionwas added 2 mL 50% NaOH
  5. temperatureThe mixture was heated
  6. temperatureto reflux for 30 minutes
  7. temperatureThe mixture was cooled to room temperature
  8. additionphenolphthalein was added
  9. additionWater was added
  10. customthe precipitated solid was collected
  11. temperatureThe mother liquor was heated again

Sources & evidence

ORD record
ord-5cc8d2038375438aad209350cbd8c9a8
Source dataset
uspto-grants-1993_04
Patent number
US05202322

Reaction notes

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