Trifluoroacetic acid → 2-[(1S)-1-Aminopropyl]-5-fluoro-3-phenyl-4(3H)-quinazolinone

HRID 1625137Notes

Reaction equation

HRID 1625137 reaction equation
C(OC(=O)[NH:7][C@H:8]([C:11]1[N:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:19](=[O:27])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2[F:28])[N:12]=1)[CH2:9][CH3:10])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[NH2:7][C@H:8]([C:11]1[N:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:19](=[O:27])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2[F:28])[N:12]=1)[CH2:9][CH3:10]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59841048tert-butyl N-[(1S)-1-(5-fluoro-4-oxo-3-phenylquinazolin-2-yl)propyl]carbamate

Product 1

HCID 598410522-[(1S)-1-Aminopropyl]-5-fluoro-3-phenyl-4(3H)-quinazolinoneYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of compound 110 (85 mmol) in dichloromethane (60 mL) was treated with trifluoroacetic acid (60 mL). The reaction mixture was stirred for 1 h, concentrated in vacuo, and partitioned between dichloromethane (150 mL) and 10% K2CO3 (sufficient amount to keep the pH greeted than 10). The aqueous layer was extracted with additional dichloromethane (100 mL), and the combined organic layers were washed with water (50 mL) and brine (50 mL). After drying with Mg SO4, the solution was concentrated to provide compound 111 as an off-white solid (22 g, 88%). 1H NMR (300 MHz, CDCl3) δ 7.73-7.65 (m, 1H); 7.62-7.49 (m, 4H), 7.32-7.22 (m, 2H), 7.13-7.06 (m, 1H), 3.42 (dd, J=7.5, 5.2 Hz, 1H), 1.87-1.70 (m, 1H), 1.58-1.43 (m, 1H), 0.80 (t, J=7.4 Hz, 3H). ESI-MS m/z 298.2 (MH+). The reaction described above and compound III are shown below.

Workup

  1. concentrationconcentrated in vacuo
  2. custompartitioned between dichloromethane (150 mL) and 10% K2CO3 (sufficient amount
  3. extractionThe aqueous layer was extracted with additional dichloromethane (100 mL)
  4. washthe combined organic layers were washed with water (50 mL) and brine (50 mL)
  5. dry with materialAfter drying with Mg SO4
  6. concentrationthe solution was concentrated

Sources & evidence

ORD record
ord-2c61fa97ba404fb08c97a8a934af1e4f
Source dataset
uspto-grants-2014_07
Patent number
US08779131B2

Reaction notes

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