Реакция #585348

Уравнение реакции

glucosamine hydrochloride

DIPEA

glucosamine hydrochloride

PyBOP

→

1-hydroxybenzotriazole

benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate

Растворители

DMF

DMF

Условия реакции

Обработка

1. 1
   workup.ADDITIONwas added
2. 2
   workup.STIRRINGThe reaction was stirred an additional 30 minutes
3. 3
   Другоеthen precipitated into acetonitrile
4. 4
   ДругоеThe solid was collected by centrifugation
5. 5
   workup.ADDITIONtreated with 200 uL piperidine for 30 minutes
6. 6
   ДругоеPrecipitation into ether
7. 7
   Промывкаthe solid washed with acetonitrile

Методика

Nvan-(N-Fmoc-2-n-decylaminoethyl) vancomycin (100 mg, 48 umol, 1.0 eq) was dissolved in 1 mL DMF and glucosamine hydrochloride was added (31 mg, 144 umol, 3.0 eq). The mixture was stirred vigorously for 30 minutes (the glucosamine hydrochloride did not fully dissolve), DIPEA (60 uL, 344 umol, 7.2 eq) was added and the mixture stirred vigorously for a further 30 minutes. A solution of benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBOP, 50 mg, 96 umol, 2.0 eq) and 1-hydroxybenzotriazole (14 mg, 104 umol, 2.2 eq) in 500 uL DMF was prepared. The PyBOP solution was added in 5 batches of 60 uL at intervals of 5 minutes to the vigorously stirred suspension of the other reaction components. The reaction was stirred an additional 30 minutes then precipitated into acetonitrile. The solid was collected by centrifugation, taken up in 1 mL N,N-dimethylformamide and treated with 200 uL piperidine for 30 minutes. Precipitation into ether was followed by centrifugation and the solid washed with acetonitrile. Reverse-phase preparative HPLC (10-70% acetonitrile in water containing 0.1% trifluoroacetic acid over 120 minutes) gave a compound of formula III where R15 is —CH2CH2—NH—(CH2)9CH3 and R22 is —N-(D-glucosamine as its trifluoroacetate salt.

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