Isopropylamine → 8-bromo-3-cyclopropyl-7-fluoro-2-(isopropylamino)quinazolin-4(3H)-one

HRID 1056378Notes

Reaction equation

HRID 1056378 reaction equation
[Br:1][C:2]1[C:3]([F:17])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9](Cl)[N:8]([CH:13]1[CH2:15][CH2:14]1)[C:7]2=[O:16].[CH:18]([NH2:21])([CH3:20])[CH3:19]>CN1C(=O)CCC1>[Br:1][C:2]1[C:3]([F:17])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:21][CH:18]([CH3:20])[CH3:19])[N:8]([CH:13]1[CH2:15][CH2:14]1)[C:7]2=[O:16]

Participants

4

Reactant 2

HCID 6363IsopropylamineHCID 897819758-bromo-2-chloro-3-cyclopropyl-7-fluoroquinazolin-4(3H)-one

Product 1

HCID 897819498-bromo-3-cyclopropyl-7-fluoro-2-(isopropylamino)quinazolin-4(3H)-oneYield 92.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A slurry of 8-bromo-2-chloro-3-cyclopropyl-7-fluoroquinazolin-4(3H)-one (721; 0.080 g, 0.252 mmol) in isopropylamine (Aldrich; 0.541 ml, 6.30 mmol) and 0.2 mL NMP was heated in a sealed tube in a biotage initiator microwave to 100° C. for 20 min. The reaction was partitioned between water and EtOAc. The organic layer was washed with water once, satd aq NaCl once, and the organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 8-bromo-3-cyclopropyl-7-fluoro-2-(isopropylamino)quinazolin-4(3H)-one (0.079 g, 0.232 mmol, 92% yield) as a brown solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 7.89 (1H, dd, J=8.8, 6.5 Hz), 7.01 (1H, t, J=8.7 Hz), 6.85 (1H, d, J=7.6 Hz), 4.41 (1H, dq, J=13.6, 6.7 Hz), 2.64-2.79 (1H, m), 1.30 (6H, d, J=6.7 Hz), 1.19-1.27 (2H, m), 0.71-0.79 (2H, m). m/z (ESI, +ve ion) 340.0/342.0 (M+H)+.

Workup

  1. customThe reaction was partitioned between water and EtOAc
  2. washThe organic layer was washed with water once
  3. dry with materialthe organics were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e553d0e9f976480a9216b9318b534ccc
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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