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8th March 2013 @ 10:57

 

Following the procedure of Amination of PT-1-4 (PT-1-9), crude product Resynthesis of MD 6-3 (PT-1-4) (120 mg, 62% purity, 0.2 mmol) was suspended in 1ml of dry dichloromethane and to this was added dry dimethylformamide (1 equivalent, 14 mg, 15 ul, ca. 1 drop) followed by dropwise oxalyl chloride (8 equivalents, 203 mg, 137 uL). The reaction mixture was stirred at room temperature under an atmosphere of dry nitrogen overnight, whereupon TLC indicated generation of the acid chloride. The reaction mixture was diluted with dichloromethane (25 ml) and washed with water (25 ml), then dried over MgSO4 and concentrated in vacuo to give a brown oil (ca. 130 mg). This oil was suspended in dry pyridine (10 ml) and to this was added glycine methyl ester hydrochloride (5 eq, 1 mmol, 126 mg). The reaction mixture was stirred at room temperature for three hours, whereupon TLC indicated consumption of the acid chloride (Rf = 0.6, 1:1 ethyl acetate:heptane, PT-1-11-A1 TLC, left-hand spot) with concommitant appearance of a new product (Rf = 0.3, 1:1 ethyl acetate:heptane, PT-1-11-A1 TLC, right-hand spot). The solvents were removed in vacuo and the residue purified by DCVC (gradient, ethyl acetate/heptane, 25, 33, 41, 50, 66, 83, 100%) to givea tan oil (16.6 mg, 48 umol, 24%)

 Risk Assessment as in Amination of PT-1-4 (PT-1-9)

Analysis:

PT-1-11-C1 13C.pdf
PT-1-11-C1 1H.pdf

1H and 13C were consistent with desired product plus some solvent residual peaks. By analogy to the N-methyl analogue previously prepared Resynthesis of MD 6-3 (PT-1-4), the CH3 peak at 2.9 ppm is no longer present. 

 

Additional Observations: crude samples decomposed in NMR tubes at room temperature with indirect sunlight over the course of 72 hours. Reduced yield due to the second step not going to completion; TLC indicated absence of SM but may have been present as the activated ester pyridinium complex.

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Attached Files
PT-1-11.png
PT-1-11-A1 TLC.jpg
PT-1-11-C1 1H.pdf
PT-1-11-C1 13C.pdf
ThomsonPatrick_ptm111c1_210313_1H-13C_av500.tar