Réaction #1755491

Équation de réaction

Boc-alanine

6-(4-chlorophenyl)-3-(4-((3,3-difluoro-1-hydroxycyclobutyl)methoxy)-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one

N,N′-diisopropylcarbodiimide

→

(S)-1-((4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)methyl)-3,3-difluorocyclobutyl 2-(tert-butoxycarbonylamino)propanoate

Rendement 88.0%

Solvants

CH2Cl2

Conditions de réaction

Traitement

1. 1
   TempératureAfter cooling to RT
2. 2
   Autreremoval of the volatiles under vacuum

Mode opératoire

A mixture of Boc-alanine (94 mg, 0.495 mmol), 6-(4-chlorophenyl)-3-(4-((3,3-difluoro-1-hydroxycyclobutyl)methoxy)-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one (50 mg, 0.099 mmol) from Example 2,4-pyrrolidinopyridene (14.68 mg, 0.099 mmol) and N,N′-diisopropylcarbodiimide (0.077 mL, 0.495 mmol) in CH2Cl2 (4 mL) was stirred at 40° C. in a sealed tube for 18 hours. After cooling to RT and removal of the volatiles under vacuum, the crude product was subjected to gradient chromatography (silica gel/EtOAc/hexane 0 to 30%) to afford (S)-1-((4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)methyl)-3,3-difluorocyclobutyl 2-(tert-butoxycarbonylamino)propanoate (59 mg, 0.087 mmol, 88% yield) as off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.13 (1 H, s), 7.66 (2 H, d), 7.54 (1 H, s), 7.46 (2 H, d), 6.87-7.06 (3 H, m), 4.96 (1 H, br. s.), 4.34-4.48 (2H, m), 4.20-4.34 (1 H, m), 3.87 (3 H, s), 3.09-3.24 (2 H, m), 2.97 (2 H, broad s.), 1.45 (9 H, s), 1.38 (3 H, d, J=7.30 Hz). LC-MS: 2.72 min 677 (M+H). Luna 5 u C18 30×4.6 mm ID, flow rate=4 ml/min., gradient=0% A to 100% B in 2 min., A=90% H2O/10% MeOH/0.1% TFA, B=10% H2O/90% MeOH/0.1% TFA).

Source