Isopropylamine → HCID 89781930, compound

HRID 1056285Notes

Reaction equation

HRID 1056285 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9](SC)[N:8]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1)[C:7]2=[O:20].ClC1C=C(C=CC=1)C(OO)=O.[CH:32]([NH2:35])([CH3:34])[CH3:33]>C(Cl)Cl.C([O-])(O)=O.[Na+].O>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:35][CH:32]([CH3:34])[CH3:33])[N:8]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1)[C:7]2=[O:20]

Participants

7

Reactant 3

HCID 6363IsopropylamineHCID 70297m-Chloroperbenzoic acidHCID 89782132HCID 89782132, compound

Product 1

HCID 89781930HCID 89781930, compoundYield 38.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 8-bromo-2-(methylthio)-3-(pyridin-2-yl)quinazolin-4(3H)-one (179 mg, 0.514 mmol, 415c) in DCM (5.1 mL) was set stirring and 3-chloroperoxybenzoic acid (127 mg, 0.565 mmol, 77% max.; Sigma Aldrich) was added. The mixture was stirred for 4 h to give a mixture of sulfone and sulfoxide. The reaction mixture was diluted with saturated aqueous NaHCO3 and extracted with DCM. The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure to give a yellow residue. The residue and isopropylamine (1.7 mL, 19.73 mmol) was set stirring at 80° C. for 30 min. The reaction was cooled to RT and diluted with water. The mixture was extracted with DCM and dried over Na2SO4. Silica was added, and the material was adsorbed under reduced pressure. It was purified on 12 g SiO2 (eluent: 0-100% EtOAc/hexanes over 25 min, RediSep Gold). The product fractions were combined and concentrated under reduced pressure to give 8-bromo-2-(isopropylamino)-3-(pyridin-2-yl)quinazolin-4(3H)-one (71 mg, 30% for 2 steps). 1H NMR (400 MHz, DMSO-d6) ppm 8.69 (1H, dd, J=4.79, 1.08 Hz) 8.08 (1H, td, J=7.73, 1.76 Hz) 7.97 (1H, dd, J=7.63, 1.37 Hz) 7.88 (1H, dd, J=7.92, 1.47 Hz) 7.55-7.63 (2H, m) 7.03 (1H, t, J=7.73 Hz) 5.90 (1H, d, J=7.63 Hz) 1.15 (6H, d, J=6.65 Hz). m/z (ESI, +ve) 360.8 (M+H)+.

Workup

  1. stirringThe mixture was stirred for 4 h
  2. customto give
  3. extractionextracted with DCM
  4. dry with materialThe combined organics were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give a yellow residue
  8. extractionThe mixture was extracted with DCM
  9. dry with materialdried over Na2SO4
  10. additionSilica was added
  11. customIt was purified on 12 g SiO2 (eluent: 0-100% EtOAc/hexanes over 25 min, RediSep Gold)
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6f5bd05d7d524610b4b798684ce3001b
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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