4-Methylmorpholine → 4-[4-(chloromethyl)-1,3-thiazol-2-yl]-N-(4-pentylbenzyl)benzamide

Temperature

0 °C

N-methylmorpholine (1.7 mL, 15.3 mmol) and isobutyl chloroformate (1.0 mL, 7.65 mmol) were added to a solution of 4-[4-(chloromethyl)-1,3-thiazol-2-yl]benzoic acid (1.85 g, 7.29 mmol) in anhydrous THF (30 mL) at 0° C. The reaction mixture was stirred at 0° C. for 30 min, then (4-pentylbenzyl)amine hydrochloride (1.64 g, 7.65 mmol) was added neat. The reaction mixture was stirred for 15 min at 0° C., then 2 hours at RT. The reaction mixture was diluted with DCM (100 mL) and washed with 1M aqueous HCl (50 mL), then saturated aqueous NaHCO3 (50 mL). The aqueous layers were extracted with DCM (100 mL). The combined organic layers were dried over MgSO4 and the solvents were removed under reduced pressure to give a brown solid. Recrystallization from a mixture MeOH/water gave 2.30 g (75%) of the title compound as beige solid. HPLC, Rt: 5.2 min (purity: 98.0%). 1H NMR (CDCl3) δ: 8.01 (d, J=8.3 Hz, 2H), 7.86 (d, J=8.3 Hz, 2H), 7.37 (s, 1H), 7.30 (d, J=8.0 Hz, 2H), 7.19 (d, J=8.0 Hz, 2H), 6.47 (m, 1H), 4.76 (s, 2H), 4.63 (d, J=5.5 Hz, 2H), 2.61 (t, J=7.7 Hz, 2H), 1.63 (m, 2H), 1.34 (m, 4H), 0.90 (t, J=6.8 Hz, 3H).

1. stirringThe reaction mixture was stirred for 15 min at 0° C.
2. custom2 hours
3. customat RT
4. washwashed with 1M aqueous HCl (50 mL)
5. extractionThe aqueous layers were extracted with DCM (100 mL)
6. dry with materialThe combined organic layers were dried over MgSO4
7. customthe solvents were removed under reduced pressure
8. customto give a brown solid
9. customRecrystallization from a mixture MeOH/water

ORD record

ord-df5d0f2a6e214668883ccc595aeb5a33

Source dataset

uspto-grants-2008_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07365225B2