Water → tert-Butyl 4-[N-[7-Chloro-2-hydroxymethyl-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate

HRID 47852Notes

Reaction equation

HRID 47852 reaction equation
C([O:4][CH2:5][C:6]1[N:15]([CH3:16])[C:14](=[O:17])[C:13]2[C:8](=[CH:9][C:10]([Cl:36])=[C:11]([CH2:18][N:19]([C:23]3[CH:35]=[CH:34][C:26]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[CH:25][CH:24]=3)[CH2:20][C:21]#[CH:22])[CH:12]=2)[N:7]=1)(=O)C.[OH-].[Na+].O>O1CCCC1>[Cl:36][C:10]1[CH:9]=[C:8]2[C:13]([C:14](=[O:17])[N:15]([CH3:16])[C:6]([CH2:5][OH:4])=[N:7]2)=[CH:12][C:11]=1[CH2:18][N:19]([C:23]1[CH:24]=[CH:25][C:26]([C:27]([O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:28])=[CH:34][CH:35]=1)[CH2:20][C:21]#[CH:22]

Participants

5

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 11124056tert-Butyl 4-(((2-(acetoxymethyl)-7-chloro-3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)methyl)(prop-2-ynyl)amino)benzoate

Product 1

HCID 10950743tert-Butyl 4-[N-[7-Chloro-2-hydroxymethyl-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 4-[N-[2-acetoxymethyl-7-chloro-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate (0.47 g, 0.92 mmol) in tetrahydrofuran (18 ml), was slowly added 1N aqueous NaOH (1.84 ml, 1.84 mmol) followed by water (1.5 ml). The slightly cloudy solution was stirred at room temperature for 1 hour, the solvent was removed in vacuo and the residue was treated with water (35 ml). The pH was adjusted to 4.5 with 1N HCl and the mixture was extracted with ethyl acetate (3×60 ml). The organics were combined, dried (Na2SO4), and concentrated in vacuo. Purification by column chromatography, on elution with 50% ethyl acetate in dichloromethane, afforded a white solid which was reprecipitated from dichioromethane (minimum amount)/hexanes. The solid was collected by filtration and dried in vacuo over P2O5 (0.345 g, 80%), mp 109-111° C.; 1H-NMR (DMSO-d6); 1.49 (s, 9H, CO2But), 3.50 (s, 3H, N3-Me), 3.25 (s (poorly resolved triplet), 1H, C≡CH), 4.40 (s, 2H, CH2C≡C), 4.57 (d, J=5.70 Hz, 2H, 2-CH2OH), 4.80 (s, 2H, 6-CH2), 5.67 (t, J=6.4 Hz, 1H, CH2OH), 6.78 (d, J=8.80 Hz, 2H, 3′,5′-ArH), 7.72 (d, J=8.44 Hz, 2H, 2′,6′-Ar), 7.82, 7.87 (2×s, 2H, 5-H, 8-H); MS (FAB, m/z) 467, 469 (M+, 95%, 45% respectively; Cl isotopic pattern).

Workup

  1. customthe solvent was removed in vacuo
  2. additionthe residue was treated with water (35 ml)
  3. extractionthe mixture was extracted with ethyl acetate (3×60 ml)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customPurification by column chromatography
  7. washon elution with 50% ethyl acetate in dichloromethane
  8. customafforded a white solid which
  9. customwas reprecipitated from dichioromethane (minimum amount)/hexanes
  10. filtrationThe solid was collected by filtration
  11. dry with materialdried in vacuo over P2O5 (0.345 g, 80%), mp 109-111° C.

Sources & evidence

ORD record
ord-8dd6c0e71c694b6fa9395f6e9f8df914
Source dataset
uspto-grants-2004_03
Patent number
US06699861B1

Reaction notes

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