PyBOP

Fig. 32 Fluorous mixture synthesis of fused-tricyclic hydantoins. Reagents and conditions a Mo(CO)6, DMSO, toluene, MW 150 °C, 35 min, closed system b TFA CH2CI2 (1 1), rt c PhC2H4NH2, PyBOP, i-Pr2EtN, MeOH, CH2CI2 followed by flash chromatography and F-HPLC d i-Pr2EtN, MeOH, MW 140 °C, 40 min, followed by F-SPE...

PyBop l-Benzotriazolyloxy(tripyrrolidino)phosphonium hexafluoro-phosphate... 

PyBOP 0-Benzotriazol-l -yloxytris(pyrrolidino)phosphonium hexafluorophosphate... 

Wang resin was purchased from Advanced ChemTech (1% DVB, 0.70mmol/g substitution, 100-200 mash, Cat. SA5009). Anhydrous tetrahydrofuran (THF), A/A-dimcthyl-formamide (DMF), methanol, dichloromethane, pyridine, 1,1 -carbonyldiimidazole (CDI), piperazine, homopiperazine, trans-1,4-diaminocyclohexane, 4-(dimethylamino)pyridine (DMAP), succinic anhydride, diglycolic anhydride, 3-methyl-glutaric anhydride, 2-aminophenol, 2-amino-p-cresol, 2-amino-4-tert-butyl phenol, /V-methylmorpholine (NMM), triphenylphosphine, diethyl azodicarboxylate (DEAD), and trifluoroacetic acid (TFA) were purchased from Aldrich Chemical Company, Inc. and used without further purification. PyBOP was purchased from Novabiochem. 

Stock solutions of amines 6-10 in DMA were prepared by dissolving 4.14 mmol of each amine in 11 mL DMA and 1 mL Hiinig s base (10 mL DMA/2mL Hiinig s base were used for the hydrochloride salt 10). Aliquots, 1.00 mL (0.345 mmol), of the appropriate amine solution were added to each reactor followed by 1.00 mL 0.345 M PyBOP in DMA (0.345 mmol). The resins were mixed for 2h and drained then equal amounts of amine and PyBOP solutions were added and the resins were mixed for another 1 h (note 7). The reactions were drained and washed with DMA (5 x 2mL), MeOH (5 x 2mL), and DMF (10 x 2mL). 

FIGURE 2.19 Pyrrolidino instead of dimethylamino substitutents for the environmental acceptability of phosphonium and carbenium salt-based reagents.56 Tetramethylurea from O-benzotriazol- l -yl/V./V./V./V -tetramethyluronium hexafluorophosphate and tetrafluoroborate is more volatile and is cytotoxic. The product released from PyBOP is not environmentally objectionable. PyBOP = benzotriazol-l-yl-oxytripyrrolidinophosphonium hexafluorophosphate. 

J Coste, D Le-Nguyen, B Castro. PyBOP A new peptide coupling reagent devoid of toxic by-product. Tetrahedron Lett 31, 205, 1990. 

BOP, PyBOP, HBTU, HATU, and so forth with an additive It has been considered essential to use an additive with these reagents because the tertiary amine required to effect the coupling promotes isomerization. Diisopropylethylamine or possibly trimethylpyridine are the bases of choice to minimize the side reaction, but the additive may increase isomerization (see Section 7.18). 

PyBOP = BtOPt(Pyr)3PE6 PyAOP = aBtOP (Pyr)3PF6 ... 

Use an onium salt-based reagent such as PyBOP, T/HBTU (see Sections 2.18-2.21), PyAOP (see Section 7.19), or other with me corresponding additive and diisopropylethylamine or trimethylpyridine as tertiary amine without an excess. The additive may, however, promote epimerization. 

PyBOP benzotriazole-l-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate TBS tert-butyldimethylsilyl... 

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