(1-Methylcyclopropyl)amine hydrochloride → 8-bromo-3-ethyl-7-fluoro-2-((1-methylcyclopropyl)amino)quinazolin-4(3H)-one

HRID 1056427Notes

Reaction equation

HRID 1056427 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].Cl.[CH3:18][C:19]1([NH2:22])[CH2:21][CH2:20]1>CS(C)=O>[Br:1][C:2]1[C:3]([F:16])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:22][C:19]1([CH3:18])[CH2:21][CH2:20]1)[N:8]([CH2:13][CH3:14])[C:7]2=[O:15]

Participants

4

Reactant 2

HCID 12953687(1-Methylcyclopropyl)amine hydrochlorideHCID 897939068-Bromo-2-chloro-3-ethyl-7-fluoro-quinazolin-4-one

Product 1

HCID 897939808-bromo-3-ethyl-7-fluoro-2-((1-methylcyclopropyl)amino)quinazolin-4(3H)-oneYield 81.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 8-bromo-2-chloro-3-ethyl-7-fluoroquinazolin-4(3H)-one (512c; 200 mg, 0.655 mmol), 1-methylcyclopropanamine hydrochloride (Small Molecules, Inc.; 211 mg, 1.964 mmol), and TEA (0.274 mL, 1.964 mmol) in DMSO (1.5 mL) was heated in a sealed microwave vial at 90° C. for 30 min. The reaction mixture was then partitioned between DCM (60 mL) and water (40 mL). The organic layer was separated and sequentially washed with water (2×40 mL) and brine (40 mL), then dried over Na2SO4, filtered, and concentrated in vacuo to give 8-bromo-3-ethyl-7-fluoro-2-((1-methylcyclopropyl)amino)quinazolin-4(3H)-one (181.1 mg, 0.532 mmol, 81% yield) as a light-yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.06 (1H, dd, J=8.8, 6.1 Hz), 6.93 (1H, t, J=8.5 Hz), 4.84-5.23 (1H, m), 4.02 (2H, q, J=6.4 Hz), 1.61 (3H, s), 1.30 (3H, t, J=7.2 Hz), 0.91 (2H, br. s.), 0.81-0.88 (2H, m). 19F NMR (376 MHz, CDCl3) δ ppm −96.57 (1F, br. s.). m/z (ESI, +ve) 339.8/341.9 (M+H)+.

Workup

  1. customThe reaction mixture was then partitioned between DCM (60 mL) and water (40 mL)
  2. customThe organic layer was separated
  3. washsequentially washed with water (2×40 mL) and brine (40 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7b9edb38657644b18035b8d294fe7dfe
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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