The oil was purified by Prep LC (12 g silica, 100% DCM to 90:9:1 DCM/MeOH/NH3) to provide the product as a white solid. To a solution of the acid (5.00 g, 32.0 mmol) in ACN (22.9 mL) was added TEA (9.82 mL, 70.5 mmol) followed by HATU (12.8 g, 33.6 mmol). of acid). The reaction was stirred at 60 C for 2h, after which time it was diluted with EtOAc and washed with 10% LiCl (3x) and brine (1x). The resulting crude orange solid was adsorbed onto a plug of silica gel and purified by chromatography (0-25% EtOAc/heptane) to provide the product as a yellow liquid. [5.050 g, 79%], [Patent Reference: WO2015129926, page 124, (21.5 MB)], To a solution of the amine (0.18 g, 0.5 mmol), HATU (0.4 g, 1.1 mmol), and DIEA (0.5 mL, 4.0 mmol) in DMA (5 mL) was added the acid (0.1 mL, 1.05 mmol). HATU is commonly encountered in amine acylation reactions (i.e., amide formation). HATU was first reported by Louis A. Carpino in 1993 as an efficient means of preparing active esters derived from 1-hydroxy-7-azabenzotriazole (HOAt). Phase separation was achieved via Whatman filter. The mixture was stirred for 90 min at RT, after which time it was added over 25 min to a solution of the amine (200 mg, 0.400 mmol) in THF (1.5 mL) at RT under N2. The crude residue was purified by silica gel chromatography (10-30% EtOAc/hexane) to provide the product as a light colored oil. A list of common conditions for the conversion of an amine to an amide via coupling reactions. The acid (152 mg, 0.801 mmol) was added to a solution of CDI (130 mg, 0.801 mmol) in dry THF (1 mL) at RT under N2. The mechanism is shown using the more commonly encountered and commercially available iminium isomer; a similar mechanism, however, is likely to apply to the uronium form. The OAt anion rapidly attacks the isouronium salt, affording the OAt-active ester and liberating a stoichiometric quantity of tetramethylurea. Key Points: Base is needed for the rxn to proceed. [250 mg, 63%], [Patent Reference: WO2014149164, page 278, (23.7 MB)], To a solution of the acid (120 mg), amine (1.1 equiv), DIEA (3 equiv), and DMF (1 mL) was added HATU (1.1 equiv). The mixture was stirred for 90 min at RT, after which time it was added over 25 min to a solution of the amine (200 mg, 0.400 mmol) in THF (1.5 mL) at RT under N2. The reaction mixture was stirred at RT for 18 h. [48.0 mg, 39%], [Patent Reference: WO2014149164, page 261, (23.7 MB)], To a solution of the acid (68 g, 0.34 mol) in DCM (1 L) was added the amine (39 g, 0.40 mol), HATU (152 g, 0.40 mol), and DIEA (130.3 g, 1.01 mol). The reaction mixture was stirred at RT for 18 h. The mixture was diluted with EtOAc (100 mL) and washed with 1N HCl (2 x 100 mL), sat. A detailed mechanism illustrating the conversion of an amine to amide 3-(ethyliminomethyleneamino)-N,N-dimethylpropan-1-amine (EDC) and hydroxybenzotriazole (HOBt). The resulting HOAt anion reacts with the newly formed activated carboxylic acid derived intermediate to form an OAt activated ester. NaCl (5 x 100 mL), dried (Na2SO4), and concentrated. A mild, versatile, copper-catalyzed three-component coupling of organoindium reagents with imines and acid chlorides provides α-substituted amides or N-protected amines in a single step with the sole byproduct being indium trichloride. To a solution of the acid (5.00 g, 32.0 mmol) in ACN (22.9 mL) was added TEA (9.82 mL, 70.5 mmol) followed by HATU (12.8 g, 33.6 mmol). The acid (152 mg, 0.801 mmol) was added to a solution of CDI (130 mg, 0.801 mmol) in dry THF (1 mL) at RT under N2. [4], 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate, InChI=1S/C10H15N6O.F6P/c1-14(2)10(15(3)4)17-16-9-8(12-13-16)6-5-7-11-9;1-7(2,3,4,5)6/h5-7H,1-4H3;/q+1;-1, InChI=1/C10H15N6O.F6P/c1-14(2)10(15(3)4)17-16-9-8(12-13-16)6-5-7-11-9;1-7(2,3,4,5)6/h5-7H,1-4H3;/q+1;-1, CN(C)C(=[N+](C)C)On1c2c(cccn2)nn1.F[P-](F)(F)(F)(F)F, Except where otherwise noted, data are given for materials in their, 10.1002/1521-3773(20020201)41:3<441::AID-ANIE441>3.0.CO;2-N, https://en.wikipedia.org/w/index.php?title=HATU&oldid=962040439, Pages using collapsible list with both background and text-align in titlestyle, Articles containing unverified chemical infoboxes, Creative Commons Attribution-ShareAlike License, This page was last edited on 11 June 2020, at 19:37. The mixture was stirred at RT for 15 min, after which time the dark clear mixture was treated with the amine (3.44 g, 35.2 mmol). The resulting material was triturated in n-pentane to provide the product as a brown gummy solid. HATU is commonly encountered in amine acylation reactions (i.e., amide formation).

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