Tert-Butylamine → 8-bromo-2-(tert-butylamino)-3-ethyl-7-fluoroquinazolin-4(3H)-one

HRID 1056426Notes

Reaction equation

HRID 1056426 reaction equation
[Br:1][C:2]1[C:3]([F:16])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9](Cl)[N:8]([CH2:13][CH3:14])[C:7]2=[O:15].[C:17]([NH2:21])([CH3:20])([CH3:19])[CH3:18]>CN1C(=O)CCC1>[Br:1][C:2]1[C:3]([F:16])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:21][C:17]([CH3:20])([CH3:19])[CH3:18])[N:8]([CH2:13][CH3:14])[C:7]2=[O:15]

Participants

4

Reactant 2

HCID 6385Tert-ButylamineHCID 897939068-Bromo-2-chloro-3-ethyl-7-fluoro-quinazolin-4-one

Product 1

HCID 897939108-bromo-2-(tert-butylamino)-3-ethyl-7-fluoroquinazolin-4(3H)-oneYield 93%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 8-bromo-2-chloro-3-ethyl-7-fluoroquinazolin-4(3H)-one (512c, 197 mg, 0.645 mmol), tert-butylamine (Aldrich; 1.5 mL, 14.27 mmol), and NMP (0.5 mL) was heated in a sealed microwave vial at 100° C. for 30 min. The reaction mixture was then partitioned between EtOAc (60 mL) and water (40 mL). The organic layer was separated and sequentially washed water (40 mL) and brine (40 mL), then dried over Na2SO4, filtered, and concentrated in vacuo to give as a yellow solid. The combined aqueous layers were subsequently extracted with DCM (2×30 mL), and the combined organic extracts were then sequentially washed with water (2×40 mL) and brine (40 mL), dried over Na2SO4, filtered, and concentrated in vacuo to provide a yellow solid. Combination of the two batches of isolated solids afforded 8-bromo-2-(tert-butylamino)-3-ethyl-7-fluoroquinazolin-4(3H)-one (204.3 mg, 0.597 mmol, 93% yield) as a light-yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.05 (1H, dd, J=8.8, 6.1 Hz), 6.89 (1H, t, J=8.5 Hz), 4.56 (1H, br. s.), 4.05 (2H, q, J=7.2 Hz), 1.62 (9H, s), 1.33 (3H, t, J=7.2 Hz). 19F NMR (376 MHz, CDCl3) δ ppm −96.81 (1F, s). m/z (ESI, +ve) 341.9/343.9 (M+H)+.

Workup

  1. customThe reaction mixture was then partitioned between EtOAc (60 mL) and water (40 mL)
  2. customThe organic layer was separated
  3. dry with materialsequentially washed water (40 mL) and brine (40 mL), then dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give as a yellow solid
  7. extractionThe combined aqueous layers were subsequently extracted with DCM (2×30 mL)
  8. washthe combined organic extracts were then sequentially washed with water (2×40 mL) and brine (40 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto provide a yellow solid

Sources & evidence

ORD record
ord-8a2f7677420545419250882c6c5fbfc7
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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