Water → 8-bromo-3-cyclopropyl-2-((1-methylcyclopropyl)amino)-quinazolin-4(3H)-one

HRID 1056379Notes

Reaction equation

HRID 1056379 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]([CH:13]1[CH2:15][CH2:14]1)[C:7]2=[O:16].Cl.[CH3:18][C:19]1([NH2:22])[CH2:21][CH2:20]1.CCN(CC)CC.O>CS(C)=O.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[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]([CH:13]1[CH2:15][CH2:14]1)[C:7]2=[O:16]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 12953687(1-Methylcyclopropyl)amine hydrochlorideHCID 897823358-bromo-2-chloro-3-cyclopropylquinazolin-4(3H)-one

Product 1

HCID 897937848-bromo-3-cyclopropyl-2-((1-methylcyclopropyl)amino)-quinazolin-4(3H)-oneYield 76.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with 8-bromo-2-chloro-3-cyclopropylquinazolin-4(3H)-one (723) (200 mg, 0.67 mmol), 1-methylcyclopropanamine hydrochloride (Small Molecules, Inc.; 126 mg, 1.17 mmol) and NEt3 (0.46 mL, 3.34 mmol) in DMSO (0.5 mL). The tube was sealed and heated in an oil bath at 100° C. After 1 h, water and EtOAc were added and the layers were separated. The aqueous layer was extracted with EtOAc (2×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude material was absorbed onto a plug of silica gel and purified by silica gel chromatography (0-50% EtOAc in hexanes), to provide 8-bromo-3-cyclopropyl-2-((1-methylcyclopropyl)amino)-quinazolin-4(3H)-one (492a) (170 mg, 0.51 mmol, 76% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.02 (dd, J=8.02, 1.56 Hz, 1H), 7.84 (dd, J=7.63, 1.57 Hz, 1H), 6.96 (t, J=7.73 Hz, 1H), 5.77 (s, 1H), 2.65 (tt, J=6.75, 4.11 Hz, 1H), 1.61 (s, 3H), 1.27-1.34 (m, 2H), 0.85-0.92 (m, 4H), 0.80-0.85 (m, 2H). m/z (ES, +ve) 334.0, 336.0 (M+H)+.

Workup

  1. customA glass microwave reaction vessel
  2. customThe tube was sealed
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with EtOAc (2×)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was absorbed onto a plug of silica gel
  9. custompurified by silica gel chromatography (0-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a6bcd6ed579040839f6731fd00129675
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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