1,3-DI-BOC-2-(TRIFLUOROMETHYLSULFONYL)GUANIDINE

White solid

N, N'-Bis(tert-butoxycarbonyl)guanidine (S6; 4.38 g, 16.9 mmol, 1.00 equiv) was dissolved in CH2Cl2 (84.4 mL) at rt. The reaction mixture was cooled to −78 °C and stirred for 10 min.Then, freshly distilled Et3N (1.79 g, 17.7 mmol, 1.05 equiv) was added dropwise.Subsequently, trifluoromethanesulfonic anhydride (5.00 g, 17.7 mmol, 1.05 equiv) was added dropwise while vigorously stirring over a period of 15 min at −78 °C. The reaction mixture was warmed to rt. After 6 h, the mixture was washed with a KHSO4 solution (1.0 M), followed by H2O. The combined organic layers were dried over Na2SO4 and filtered. The solvent under reduced pressure. Purification by flash column chromatography over silica(CH2Cl2 = 100percent) furnished the title compound S7 (5.51 g, 14.1 mmol, 83percent) as a colourless solid.Under an inert atmosphere, 29 N, N-di-(tert-butoxycarbonyl)-guanidine (8) (10 g, 38 mmol) was dissolved in anhydrous 11 dichloromethane (200 mL). The mixture was cooled to −78° C., and 31 triethylamine (5.65 mL, 40.5 mmol) was added. 32 Trifluoromethanesulfonic anhydride (6.81 mL, 40.5 mmol) was added dropwise, over a 30-minute period. The reaction mixture was stirred for 16 h at room temperature. The solution was washed with 2M sodium bisulphate (1×200 mL) and water (1×200 mL), and the organic phase was dried with anhydrous sodium sulphate, filtered and concentrated. The crude product was purified by flash chromatography on silica gel (eluent: 100percent dichloromethane) and recrystallized in hexanes. 33 N, N-di-Boc-N′-trifluoromethanesulf onylguanidine was obtained as white crystals (11.74 g, 78percent). A solution of 5.2 g (20 mmol) of 1, 3-bis (TERT-BUTOXYCARBONYL) guanidine in 100 mL of dry dichloromethane was cooled to-78°C under stirring and 5.6 g (20 mmol) of trifluoromethanesulfonic anhydride were added dropwise. The reaction mixture was allowed to come to room temperature and stirred for 5 hours. An aqueous solution of NAHSO4 was added and the organic layer dried over NA2S04 and evaporated to dryness. The residue was purified by chromatography on a silica gel column (eluant petroleum ether/ethyl acetate 7/3) to give 4.0 g (51percent yield) of the title compound.Compound B was synthesized according to a previously reported procedure (Baker, Tomioka, & Goodman, 2002; Goodman, Feichtinger, & Romoff, 1998). Briefly, triethylamine (1.34 mL, 9.65 mmol, 1.25 equiv) was added to a solution of 1, 3-di-boc-guanidine (2 g, 7.72 mmol, 1 equiv) in CH[0106] Under an Ar atmosphere, intermediate 36 (1.93 g, 7.4 mmol) and triethylamine (2.1 mL, 14.8 mmol) were dissolved in anhydrous methylene chloride (15 mL). The solution was cooled to −78° C., followed by trifluoromethanesulfonic anhydride (1.9 mL, 11.6 mmol) dropwise over 10 min. The mixture was stirred at room temperature for 20 hours. After confirming completion of the reaction by TLC (ethyl acetate:n-hexane=1:4), the reaction solution was poured into a saturated aqueous ammonium chloride solution (100 mL). The mixture was extracted with methylene chloride (3×50 mL), and the organic layer was washed with water (100 mL) and saturated saline (100 mL) and then dried over anhydrous magnesium sulfate. After evaporation under a reduced pressure, the obtained material was purified by flash column chromatography (ethyl acetate:n-hexane=1:10), to give intermediate 37 (786 mg, 27percent) as a white solid. [0107] The synthesis was performed according to published procedures, as described in “The preparation of N, N-Bis(tert-butoxycarbonyl)-guanidine”. A solution of N, N-bis(tert-butoxycarbonyl)-guanidine (3.0414 g, 12.035 mmole) and triethylamine (2.0 mL) in anhydrous dichloromethane (60 mL) was cooled to −68° C. using a dry ice/acetone bath under an atmosphere of nitrogen. Triflic anhydride (2.1 mL, 12.590 mmole) was added dropwise (2.1 mL/30 minutes). After half of the triflic anhydride was added, the color became light brown and the reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction was washed with 2 M sodium bisulfate (20 mL) and water (20 mL), and then dried over anhydrous sodium sulfate. The dry organic solution was concentrated under reduced pressure and purified by chromatography on silica gel eluted with CHTert-butyl N-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate (7.12 g, 27.45 mmol, Sigma-Aldrich catalogue id: 496871 ) was dissolved in dry DCM (136 ml).

Guanidinylation reagents for amines and peptides

Molecular Weight:391.37
XLogP3:3.9
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:10
Rotatable Bond Count:7
Exact Mass:391.10249103
Monoisotopic Mass:391.10249103
Topological Polar Surface Area:132
Heavy Atom Count:25
Complexity:607
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes