Triethylamine → (S)-tetrahydrofuran-3-yl (R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate

Participants

Reaction Conditions

Reaction Steps

To tert-butyl(R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate (907.2 mg, 2.16 mmol) was added 4 mL of 1:1 TFA:CH2Cl2. The mixture was stirred at room temperature for 5 hours. The reaction was diluted with a solution of saturated aqueous NaHCO3 and CH2Cl2. The organic layer was separated, dried over Na2SO4, and concentrated under reduced pressure to give 2-(4-((R)-3-aminopyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenol. To this free amine (640 mg, 2 mmol) was added 8 ml of CH2Cl2 and triethylamine (335 μL, 2.4 mmol). After cooling the mixture to 0° C., (S)-tetrahydrofuran-3-yl chloroformate (271 mg, 1.8 mmol) was added, and the reaction was allowed to stir for 30 minutes. Purification on silica gel using 30-100% ethyl acetate/hexanes gave (S)-tetrahydrofuran-3-yl(R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate. 1H NMR (400 MHz, CDCl3) δ 14.8 (bs, 1H), 8.34 (d, J=6.4 Hz, 1H), 7.83 (d, J=4.0 Hz, 1H), 7.48 (bs, 1H), 7.27 (m, 1H), 7.08 (d, J=8.1 Hz, 1H), 6.93 (d, J=8.1 Hz, 1H), 6.82 (t, J=7.5 Hz, 1H), 5.21 (s, 1H), 5.06 (s, 1H), 4.37 (s, 1H), 4.15 (m, 1H), 4.02 (s, 1H), 3.97 (d, J=5.6 Hz, 1H), 3.87-3.77 (m, 5H), 2.42 (s, 3H), 2.24 (t, J=6.0 Hz, 1H), 2.15-2.06 (m, 1H), 1.98 (q, J=9.3 Hz, 2H).

Provenance & Evidence