2-Amino-5-methylthiazole → N-[(1S)-1-(5-Fluoropyrimidin-2-yl)ethyl]-N'-(5-methyl-1,3-thiazol-2-yl)-6-morpholin-4-yl-1,3,5-triazine-2,4-diamine

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(S)-4-chloro-N-(1-(5-fluoropyrimidin-2-yl)ethyl)-6-morpholino-1,3,5-triazin-2-amine (100 mg, 0.29 mmol), 5-methylthiazol-2-amine (50.4 mg, 0.44 mmol), BINAP (18.33 mg, 0.03 mmol), Pd2(dba)3 (13.48 mg, 0.01 mmol) and Cs2CO3 (240 mg, 0.74 mmol) were combined in a microwave reaction tube and vacuum purged. The tube was then charged with nitrogen and dioxane (0.589 mL) was added. The tube was then evacuated again and placed under a nitrogen balloon for 8 hours. LC/MS confirmed formation of the product (m+1 = 418) at t= 2.07 min. The reaction mixture was concentrated in vacuo leaing a brown solid (472 mg). This material was the redissolved in EtOAc, filtered through Celite, washed with water and dried with Na2SO4. Concentration in vacuo gave a rust solid (272 mg). This material was purified by ISCO (0-10% MeOH/DCM). Concentration of the fractions in vacuo gave an orange oil. This material was then repurifed by ISCO (4-8% MeOH/DCM) and (0-4% MeOH/DCM). Both gradients resulted in impure material, so the recovered orange oil was purified again by ISCO (60-100% EtOAc/Hex). Concentration in vacuo gave a yellow solid (34.8 mg). LC/MS showed this material to still be only 80% pure, so it was purified again by ISCO (55-95% EtOAc/Hex). A yellow solid (25.4 mg) was again collected. Although LC/MS and HPLC showed this material to be only ~80% pure, the NMR confirmed this material to be the desired product, (S)-N2-(1-(5-fluoropyrimidin-2-yl)ethyl)-N4-(5-methylthiazol-2-yl)-6-morpholino-1,3,5-triazine-2,4-diamine, with 95% purity. 1H NMR (300 MHz, CHLOROFORM- _d_ ) d ppm 11.87 (br. s., 1 H) 9.48 (br. s., 1 H) 8.58 (s, 2 H) 7.01 (s, 1 H) 5.35 (t, 1 H) 3.28 - 4.23 (m, 8 H) 2.38 (s, 3 H) 1.59 (d, 4 H)

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