Hydrochloric Acid → HCID 72202161, compound

Temperature

80 °C

SOCl2 (1.218 mL, 16.68 mmol) and DMF (208.24 μL) were added dropwise to a suspension of 3-iodo-4-(methoxycarbonyl)benzoic acid (1.0212 g, 3.34 mmol) in toluene (8.37 mL) and the RM was stirred at 80° C. for 1 h. The solvent was evaporated off under reduced pressure and the residue was dissolved in THF (6.27 mL). DIPEA (1.166 mL, 6.67 mmol) was added and the mixture was cooled down to 0° C., treated dropwise with a solution of 4-(trifluoromethoxy)aniline (0.496 mL, 3.67 mmol) in THF was added and the RM was stirred at RT for 2.5 h. The RM was treated with 1 M HCl and extracted with EtOAc. The combined extracts were washed with HCl 1 M, NaHCO3 10%, brine, dried over MgSO4 and the solvent was evaporated off under reduced pressure to give a residue, of which (500 mg, 1.075 mmol), together with pyrimidin-5-ylboronic acid (266 mg, 2.150 mmol), Pd(PPh3)2Cl2 (75 mg, 0.107 mmol), Na2CO3 (342 mg, 3.22 mmol), water (1.30 mL), EtOH (656 μL) and DME (4.58 mL), were added to a vial, which was sealed, evacuated/purged with argon and subjected to MW irradiation for 10 min at 120° C. RM was diluted with DME (3 mL) and stirred overnight with Si-Thiol (1.3 mmol/g, 413 mg, 0.537 mmol). The mixture was centrifuged, filtered and the filtrate was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (Silica gel, cyclohexane/EtOAc, 2% to 50% EtOAc) to afford the title compound as a yellow solid. UPLC-MS (Condition 2) tR=1.08 min, m/z=418.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.72 (s, 3H) 7.40 (d, J=8.21 Hz, 2H) 7.88 (m, J=9.00 Hz, 2H) 8.08 (s, 1H) 8.16 (s, 2H) 8.88 (s, 2H) 9.24 (s, 1H) 10.62 (s, 1H).

1. customThe solvent was evaporated off under reduced pressure
2. dissolutionthe residue was dissolved in THF (6.27 mL)
3. temperaturethe mixture was cooled down to 0° C.
4. additionwas added
5. stirringthe RM was stirred at RT for 2.5 h
6. extractionextracted with EtOAc
7. washThe combined extracts were washed with HCl 1 M, NaHCO3 10%, brine
8. dry with materialdried over MgSO4
9. customthe solvent was evaporated off under reduced pressure
10. customto give a residue
11. customwas sealed
12. customevacuated/purged with argon
13. customsubjected to MW irradiation for 10 min at 120° C
14. additionRM was diluted with DME (3 mL)
15. filtrationfiltered
16. customthe filtrate was evaporated off under reduced pressure
17. customto give the crude product which
18. customwas purified by flash chromatography (Silica gel, cyclohexane/EtOAc, 2% to 50% EtOAc)

ORD record

ord-a2d4fe77302c474eab9bfa8ea792376d

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09315489B2