Sodium Hydroxide → 4-amino-5-cyclopropylquinazolin-2(1H)-one

HRID 471623Notes

Reaction equation

HRID 471623 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]2[CH2:12][CH2:11]2)[C:3]=1[C:4]#[N:5].[C:13]([N:21]=C=O)(=[O:20])C1C=CC=CC=1.[OH-].[Na+]>O1CCOCC1>[NH2:5][C:4]1[C:3]2[C:2](=[CH:9][CH:8]=[CH:7][C:6]=2[CH:10]2[CH2:11][CH2:12]2)[NH:1][C:13](=[O:20])[N:21]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 78210Benzoyl isocyanateHCID 667472522-Amino-6-cyclopropylbenzonitrile

Product 1

HCID 673976364-amino-5-cyclopropylquinazolin-2(1H)-oneYield 12.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

A solution of 2-amino-6-cyclopropylbenzonitrile (Example 92a) (1.0 eq., 1.0 mmol, 158 mg) and benzoyl isocyanate (90% pure, 1.0 eq., 1.0 mmol, 1.171 g/mL, 140 μL) in dioxane (15 mL) was stirred at room temperature. After 2 hours, the volatiles were removed on a rotary evaporator. The resulting crude N-benzoyl urea was suspended in EtOH (10 mL, 200 proof) and NaOH (2.5 eq., 2.5 mmol, 1N, 2.50 mL) was added. The reaction was heated to 75° C. with stirring for 7 hours. The solvent were evaporated and the residue diluted with water (10 mL). The reaction mixture was acidified with 10% citric acid/water solution and carefully titrated to pH 7-8 with saturated NaHCO3 solution. The precipitated product was collected by vacuum filtration, washing with water. The residue was suspended in EtOH (3 mL, 200 proof) and HCl was added (12.1N, 3 mL). The mixture was heated to 90° C. for 1 hour. The reaction mixture was cooled to room temperature and diluted with water (20 mL), filtered (0.45 μm PTFE frit), and the filtrate concentrated on a rotary evaporator. The residue was further purified by preparative TLC (1000 μm, 10/90 MeOH/DCM) and trituration with methanol at room temperature. The reaction gives 25 mg (12.4%) of the title compound as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 0.802 (m, 2H), 1.086 (m, 2H), 2.345 (m, 1H), 6.922 (d, J=8 Hz, 1H), 7.000 (d, J=8 Hz, 1H), 7.253 (br. s, 1H), 7.397 (t, J=8 Hz, 1H), 8.022 (br. s, 1H), 10.644 (s, 1H). MS 202 (MH+).

Workup

  1. customthe volatiles were removed on a rotary evaporator
  2. customThe solvent were evaporated
  3. additionthe residue diluted with water (10 mL)
  4. filtrationThe precipitated product was collected by vacuum filtration
  5. washwashing with water
  6. additionHCl was added (12.1N, 3 mL)
  7. temperatureThe mixture was heated to 90° C. for 1 hour
  8. temperatureThe reaction mixture was cooled to room temperature
  9. additiondiluted with water (20 mL)
  10. filtrationfiltered (0.45 μm PTFE frit)
  11. concentrationthe filtrate concentrated on a rotary evaporator
  12. customThe residue was further purified by preparative TLC (1000 μm, 10/90 MeOH/DCM) and trituration with methanol at room temperature

Sources & evidence

ORD record
ord-046679eeb4a2430eab618539133e61a6
Source dataset
uspto-grants-2014_01
Patent number
US08633186B2

Reaction notes

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