* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
N-(7-amino-4-chloro-1-methyl-1H-indazol-3-yl)-N-(4-methoxybenzyl)methanesulfonamide[ No CAS ]
[ 205445-52-9 ]
tert-butyl (S)-(1-(3-(4-chloro-3-(N-(4-methoxybenzyl)methylsulfonamido)-1-methyl-1H-indazol-7-yl)-5,7-difluoro-4-oxo-3,4-dihydroquinazolin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
310 mg
Within a septum top vial equipped with a magnetic stirrer bar was added (S)-2- i-butoxycarbonyl)amino)-3-(3,5-difluorophenyl)propanoic acid (200 mg, 0.664 mmol), <strong>[126674-77-9]2-amino-4,6-difluorobenzoic acid</strong> (115 mg, 0.664 mmol), and diphenyl phosphite (0.449 mL, 2.323 mmol) in pyridine (1.5 mL). The vial was capped and the mixture was heated in an aluminum block for 1.5 hours at 70C. N-(7-amino-4-chloro-l-methyl-lH- indazol-3-yl)-N-(4-methoxybenzyl)methanesulfonamide (288 mg, 0.730 mmol) (Intl7d) was then added to the mixture and the cap placed on the vial, and the reaction was again heated to 70C for an additional 2 hours. LC/MS after cooling showed the desired product as a major peak. Dried down the reaction slowly under a stream of nitrogen. The residue was dissolved in DCM and was transferred to the top of a 40 g silica gel chromatography column. The desired product was eluted with 0-100% ethyl acetate/hexanes over 1.2 L of total solvent. Like fractions (TLC: Rf = 0.69; 50% ethyl acetate/hexanes) were concentrated down to give 310 mg of yellow foam. This material will used as is for next step. LC/MS m/z = 759.2 (M-55)+. Column: Waters Aquity UPLC BEH C18, 2.1 mm x 50 mm, 1.7 muiotaeta particles; Mobile Phase A: 100% water with 0.05% TFA; Mobile Phase B: 100% acetonitnle : water with 0.05% TFA; Temperature: 40 C; Gradient: 2 %B to 98 %B over 1.5 min, then a 1.5 min hold at 100 %B; Flow: 0.8 mL/min; Detection: UV (254 nm); Retention Time: 1.88 min.