1-Hydroxybenzotriazole hydrate → HCID 86709960, compound

Participants

Reaction Steps

A mixture of 2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetic acid (Example B) (328.3 mg, 1.065 mmol), (3S)-ethyl 3-amino-3-(3-chloro-5-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl)propanoate hydrochloride salt (from step 1 above) (364.2 mg, 0.968 mmol) and 1-hydroxybenzotriazole hydrate (31.5 mg, 0.206 mmol) was dissolved in a mixture of DMF/DCM (1:1) and stirred at room temperature under nitrogen atmosphere for 10 min to give a cream suspension. N,N′-diisopropylcarbodiimde (210 μL, 1.356 mmol) was added to the above suspension and the reaction mixture was stirred at room temperature overnight (19 h) under nitrogen atmosphere. The solvent was evaporated in vacuo to give a yellow-cream gummy residue. LC-MS analysis of the crude residue shows the desired product: (3S)-ethyl 3-(3-chloro-5-(1,1,1-trifluoro-2-methylpropan-2-yl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoate's mass: m/z 630 (35ClM+H) and m/z 632 (37ClM+H); Calcd for C27H31ClF3N5O7: 630.01. The crude residue is used as such for the saponification with lithium hydroxide monohydrate (Step 3)

Provenance & Evidence