(S)-2-(1-aMinopropyl)-5-fluoro-3-phenylquinazolin-4(3H)-one Chemical Properties

Boiling point:

455.3±55.0 °C(Predicted)

Density 

1.27±0.1 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2–8 °C

solubility 

Chloroform (Slightly), DMSO (Slightly), Ethanol (Sparingly)

form 

Solid

pka

8.23±0.29(Predicted)

color 

Off-White

InChI

InChI=1S/C17H16FN3O/c1-2-13(19)16-20-14-10-6-9-12(18)15(14)17(22)21(16)11-7-4-3-5-8-11/h3-10,13H,2,19H2,1H3/t13-/m0/s1

InChIKey

BNMGOWXQUZHWIO-ZDUSSCGKSA-N

SMILES

N1C2=C(C(F)=CC=C2)C(=O)N(C2=CC=CC=C2)C=1[C@@H](N)CC

(S)-2-(1-aMinopropyl)-5-fluoro-3-phenylquinazolin-4(3H)-one Usage And Synthesis

Uses

2-[(1S)-1-Aminoprpyl]-5-fluoro-3-phenyl-4(3H)-quinazolinone is used as reagent/reactant in synthetic preparation of idelalisib using the HMDS/I2-catalyzed cyclocondensation and Boc deprotection of an (aminobutyrylamino)benzamide to a nonracemic quinazoline as the key step.

Synthesis

The general procedure for the synthesis of (S)-2-(1-aminopropyl)-5-fluoro-3-phenyl-4(3H)-quinazolinone from tert-butyl (S)-(1-(5-fluoro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)propyl)carbamate was carried out as follows: the (S)-(1-(5-fluoro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl )propyl)carbamic acid tert-butyl ester (220 mg, 0.55 mmol) was dissolved in ethyl acetate (2 mL), followed by a one-time addition of an ethyl acetate solution of hydrogen chloride (2.5 mL, 3.88 M) at room temperature. The reaction mixture was stirred at room temperature overnight. Upon completion of the reaction, the resulting suspension was dissolved in water (20 mL) and the aqueous phase was extracted with ethyl acetate (20 mL) and the pH of the aqueous phase was adjusted with sodium carbonate powder to 8. Subsequently, the aqueous phase was further extracted with ethyl acetate (20 mL x 3). All organic phases were combined, washed with saturated saline (20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford (S)-2-(1-aminopropyl)-5-fluoro-3-phenyl-4(3H)-quinazolinone as a white powder (163 mg, 100% yield).

References

[1] Patent: CN104513235, 2017, B. Location in patent: Paragraph 1158; 1159; 1160; 1161
[2] Patent: CN104130261, 2016, B. Location in patent: Paragraph 0042; 0043; 0044
[3] Patent: WO2005/113554, 2005, A2. Location in patent: Page/Page column 25
[4] Patent: CN106146411, 2016, A. Location in patent: Paragraph 0035; 0036
[5] Organic Preparations and Procedures International, 2016, vol. 48, # 4, p. 337 - 341

(S)-2-(1-aMinopropyl)-5-fluoro-3-phenylquinazolin-4(3H)-one(870281-86-0)Related Product Information

• Idelalisib Impurity 8
• 2-aMino-6-fluoro-N-phenylbenzaMide hydrochloride
• 2-Amino-6-fluorobenzoic acid
• BOC-ABU-OH
• (S)-tert-butyl (1-(5-fluoro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)propyl)carbaMate
• CAL-101
• 2-Fluoro-6-nitro-N-phenylbenzamide