تفاعل #167181

معادلة التفاعل

N-methylmorpholine

2-methoxycarbonylamino-butyric acid

HATU

3-{5-[4-(6-{2-[5-(2-methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

HCl

→

title product

المردود 80.5%

[1-(6-{5-[6-(4-{2-[2-(2-Methoxycarbonylamino-butyryl)-2-aza-bicyclo[2.2.1]hept-3-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester

المردود 80.5%

المذيبات

DMF

—

dioxanes

—

dioxanes

MeOH

ظروف التفاعل

المعالجة

1. 1
   تركيزthen concentrated
2. 2
   أخرىto afford the HCL salt of the crude amine
3. 3
   workup.STIRRINGAfter stirring for overnight the reaction
4. 4
   أخرىwas quenched with formic acid
5. 5
   أخرىthen purified by reverse phase preparative HPLC (5-45% MeCN—H2O; 0.1% formic acid modifier)

الإجراء التجريبي

To 3-{5-[4-(6-{2-[5-(2-methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (60 mg, 0.077 mmol) in dioxanes (2 mL) and MeOH (0.5 mL) was added 4N HCl in dioxanes (160 μL). The suspension was stirred for 2 h then concentrated to afford the HCL salt of the crude amine. To the crude amine in DMF (1 mL) was added N-methylmorpholine (34 μL, 0.31 mmol), 2-methoxycarbonylamino-butyric acid (19 mg, 0.11 mmol) and HATU (35 mg, 0.09 mmol). After stirring for overnight the reaction was quenched with formic acid then purified by reverse phase preparative HPLC (5-45% MeCN—H2O; 0.1% formic acid modifier) to afford the title product (51 mg, 0.062 mmol, 80% yield). LCMS-ESI+: calc'd for C47H55N8O6: 827.4 (M+H+). Found: 827.4 (M+H+).

المصدر