反应详情

A mixture of 2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoic acid (620 mg, 3.05 mmol) and N,N′-dicyclohexylcarbodiimide (315 mg, 1.53 mmol) in DCM (4 ml) is stirred at RT for 30 minutes. This mixture is added to 6-(2-phenylethynyl)-4-(trifluoromethyl)pyridin-2-amine B3b (100 mg, 0.38 mmol) and DIPEA (73 μl; 0.42 mmol) in NMP (5 ml). After stirring for 6 days at 50° C. the reaction mixture is concentrated in vacuo and the boc-protected product purified by NP chromatography. The boc-protected product is treated with DCM:TFA (9:1, 4 ml) for 1.5 h at RT. This mixture is diluted with DCM and extracted with a saturated aqueous solution of NaHCO3. The combined organic layers are dried over MgSO4 and concentrated in vacuo. The product is purified by RP HPLC. Yield: 10.2 mg (8%). HPLC-MS: M+H=348; tR=1.46 (*Method—1).

1. stirringAfter stirring for 6 days at 50° C. the reaction mixture
2. concentrationis concentrated in vacuo
3. custompurified by NP chromatography
4. additionThe boc-protected product is treated with DCM:TFA (9:1, 4 ml) for 1.5 h at RT
5. additionThis mixture is diluted with DCM
6. extractionextracted with a saturated aqueous solution of NaHCO3
7. dry with materialThe combined organic layers are dried over MgSO4
8. concentrationconcentrated in vacuo
9. customThe product is purified by RP HPLC