Diisopropylethylamine → HCID 178522988, compound

HRID 606376Notes

Reaction equation

HRID 606376 reaction equation
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([O:14]CC)=O)[NH:3]1.[NH:17]1[CH:21]=[N:20][C:19]([S:22][CH2:23][CH2:24][O:25][C:26]2[CH:27]=[C:28]([CH2:32][NH2:33])[CH:29]=[CH:30][CH:31]=2)=[N:18]1.C(N(C(C)C)CC)(C)C>C(O)C>[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([NH:33][CH2:32][C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([O:25][CH2:24][CH2:23][S:22][C:19]3[N:20]=[CH:21][NH:17][N:18]=3)[CH:27]=2)=[O:14])[NH:3]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 135437466Ethyl 4-oxo-3,4-dihydroquinazoline-2-carboxylateHCID 178509870HCID 178509870, compound

Product 1

HCID 178522988HCID 178522988, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of ethyl 4-oxo-3,4-dihydro-2-quinazolinecarboxylate obtained according to the methods described in Journal of Organic Chemistry (1978), 43(23), 4485-7 and the like (200 mg, 0.917 mmol), 1-(3-{[2-(1H-1,2,4-triazol-3-ylthio)ethyl]oxy}phenyl)methanamine obtained in Reference Example 3 (298 mg, 1.19 mmol) and diisopropylethylamine (237 mg, 1.83 mmol) in ethanol (10 mL) was stirred at 90° C. for 15 hr. The reaction solvent was evaporated under reduced pressure, and the residue was extracted with ethyl acetate and water. The organic layer was washed with saturated brine, dried over sodium sulfate, and concentrated. The residue was purified by preparative HPLC (GILSON 215LIQUD HANDLER, 322PUMP, UV/VIS-156, SHISEIDO CAPCELL PACK C-18 UG120 S-5 (20 mmφ×50 mm), mobile phase: distilled water (containing 0.1% trifluoroacetic acid)/acetonitrile (containing 0.1% trifluoroacetic acid), gradient: distilled water/acetonitrile-90/10→0/100, time: 10 min, flow rate: 25 mL/min, detection wavelength: 220 nm), and the obtained crude crystals were recrystallized from ethanol to give the title compound as a white powder (29.2 mg, 8%).

Workup

  1. customobtained
  2. customThe reaction solvent was evaporated under reduced pressure
  3. extractionthe residue was extracted with ethyl acetate and water
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC (GILSON 215LIQUD HANDLER, 322PUMP, UV/VIS-156, SHISEIDO CAPCELL PACK C-18 UG120 S-5 (20 mmφ×50 mm), mobile phase
  8. distillationdistilled water (containing 0.1% trifluoroacetic acid)/acetonitrile (containing 0.1% trifluoroacetic acid)
  9. distillationgradient: distilled water/acetonitrile-90/10→0/100, time
  10. custom10 min, flow rate: 25 mL/min, detection wavelength: 220 nm), and the obtained crude crystals
  11. customwere recrystallized from ethanol

Sources & evidence

ORD record
ord-0f738390615a4aa8931993ab4ab18c92
Source dataset
uspto-grants-2011_03
Patent number
US07915267B2

Reaction notes

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