(1S)-1-(2,4-difluorophenyl)ethanamine

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared following the same general protocol as described in Step 8-9, Example 1, using the (S)-1-(2,4-difluorophenyl)ethanamine and the 1-((2′-(tert-butoxycarbonyl)-[1,1′-biphenyl]-4-yl)methyl)-2,3-dimethyl-1H-indole-5-carboxylic acid. ESI-MS (m/z): 539 [M+H]+.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound is prepared from (9-hydroxy-3,3-dimethyl-1,5-dioxa-spiro[5.5]undec-9-yl)-acetaldehyde and (S)-1-(2,4-difluoro-phenyl)-ethylamine following a procedure analogous to that described in Step 3 of Intermediate 2. Yield: 66% of theory; LC (method 5): tR=0.99 min; Mass spectrum (ESI+): m/z=384 [M+H]+.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 7 ml NMP solution of 3-(6-chloro-2-(methylthio)pyrimidin-4-yl)pyrazolo[1,5-a]pyrimidine (7h, 1.30 g) and (S)-1-(2,4-difluoro-phenyl)ethanamine (1.47 g) was heated in a microwave reactor at 220° C. for 20 min. LC/MS indicated the major peak was the desired product. The reaction mixture was partitioned between ethyl acetate and sat. NH4OAc. The organic phase was dried with MgSO4, filtered and the solvent was removed under reduced pressure. The product was purified by chromatography (SiO2, EtOAc-Hex, 1:1) (1.09 g, 58.6% yield).

反応条件: temp:220.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-(6-Chloro-2-(methylthio)pyrimidin-4-yl)-1,2-dihydropyrazolo[1,5-a]pyrimidin-2-amine (4b) (500 mg, 1.70 mmoles) was dissolved in 5 mL of NMP along with (S)-1-(2,4 difluorophenyl)-ethylamine (988 mg, 5.0 mmoles, added as the free base). The reaction mixture was heated in the microwave three times at 220° C., for 15 minutes each. The reaction progress was monitored by LC/MS. Upon completion, the reaction was quenched by addition of 1N HCl to the vigorously stirred material until a thick oily material separated. This crude mixture was centrifuged and the thick oil separated. The oily mass was transferred to a round-bottomed flask and methanol was added. Solvents were removed under reduced pressure and the resulting solid was suspended in acetonitrile, warmed to 50° C. and vigorously stirred. Then it was cooled and the resulting precipitate was suction-filtered. The filtrate was reduced to an oil under reduced pressure and then re-dissolved in a minimum amount of methanol and purified via HPLC on C18 silica with acetonitrile/water/TFA as the eluent. After lyophilizing the desired fractions a beige solid was obtained (136 mg, 19.4% yield). added as the free base) Upon completion, the reaction was quenched by addition of 1N HCl to the vigorously stirred material until a thick oily material separated the thick oil separated The oily mass was transferred to a round-bottomed flask methanol was added Solvents were removed under reduced pressure warmed to 50° C. Then it was cooled the resulting precipitate was suction-filtered re-dissolved in a minimum amount of methanol purified via HPLC on C18 silica with acetonitrile/water/TFA as the eluent was obtained (136 mg, 19.4% yield)