N-Methyl-tert-butylamine → 8-bromo-2-(tert-butyl(methyl)amino)quinazolin-4(3H)-one

HRID 1056278Notes

Reaction equation

HRID 1056278 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9](Cl)[N:8]=[C:7]2[OH:13].[CH3:14][NH:15][C:16]([CH3:19])([CH3:18])[CH3:17]>CN1C(=O)CCC1>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([N:15]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH3:14])[NH:8][C:7]2=[O:13]

Participants

4

Reactant 2

HCID 84552N-Methyl-tert-butylamineHCID 178517813HCID 178517813, compound

Product 1

HCID 1365008408-bromo-2-(tert-butyl(methyl)amino)quinazolin-4(3H)-oneYield 25%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 8-bromo-2-chloroquinazolin-4-ol (407c, 0.20 g, 0.77 mmol) in N-methyl-tert-butylamine (Aldrich; 0.919 mL, 7.71 mmol) and 1 mL NMP was sealed and heated to 150° C. in an oil bath for 6 h. The reaction was heated for 3 days. The reaction was partitioned between sat'd aq. NH4Cl and EtOAc. The organic layer was washed with sat'd aq. NH4Cl once, sat'd aq. NaCl once, and the organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The material was treated with 10% MeOH in DCM, adsorbed onto 1.5 g silica gel, and purified by silica gel chromatography (24 g column) using 0-50% EtOAc/hexanes. The product-containing fractions were concentrated to afford 8-bromo-2-(tert-butyl(methyl)amino)quinazolin-4(3H)-one (0.060 g, 0.19 mmol, 25% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.36 (1H, br. s.), 7.76-8.03 (2H, m), 6.95-7.14 (1H, m), 2.97 (3H, s), 1.55 (9H, s). m/z (ESI, +ve ion) 310.0/312.0 (M+H)+.

Workup

  1. customwas sealed
  2. temperatureThe reaction was heated for 3 days
  3. customThe reaction was partitioned between sat'd aq. NH4Cl and EtOAc
  4. washThe organic layer was washed with sat'd aq. NH4Cl once
  5. dry with materialthe organics were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. additionThe material was treated with 10% MeOH in DCM
  9. custompurified by silica gel chromatography (24 g column)
  10. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-34db385db78b4bbd8545a3f1e5c0373a
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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