tert-butyl 1,2,3,4,4a,5,7,7a-octahydropyrrolo[3,4-b]pyridine-6-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of tert-butyl hexahydro-1H-pyrrolo[3,4-b]pyridine-6(2H)-carboxylate (1.60 g), 1-bromo-3-chloropropane (1.50 mL) and K2CO3 (3.00 g) in acetone was heated to reflux for 9 h. The reaction mixture was cooled to rt and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 1:1 (v/v) PE/EA) to give the title compound as yellow oil (0.53 g, 65.00%), HPLC: 89.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 303.2 (M+1). was heated to reflux for 9 h filtered The filtrate was concentrated in vacuo the residue was chromatographed with a silica gel column (eluting agent: 1:1 (v/v) PE/EA)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of tert-butyl hexahydro-1H-pyrrolo[3,4-b]pyridine-6(2H)-carboxylate (1.60 g), 1-bromo-3-chloropropane (1.50 mL) and K2CO3 (3.00 g) in acetone was heated to reflux for 9 h. The reaction mixture was cooled to rt and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 1:1 (v/v) PE/EA) to give the title compound as yellow oil (0.53 g, 65.00%), HPLC: 89.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 303.2 (M+1). was heated to reflux for 9 h filtered The filtrate was concentrated in vacuo the residue was chromatographed with a silica gel column (eluting agent: 1:1 (v/v) PE/EA)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of tert-butyl 5H-pyrrolo[3,4-b]pyridine-6(7H)-carboxylate (1.50 g) in glycol monomethyl ether was added a catalytic amount of 10% Pd/C. The suspension was heated to 70° C. and stirred for 6 h under H2. The resulted mixture was cooled to rt, poured into 100 mL of water and extracted with CH2Cl2 (50 mL×3). The combined organic phases were dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo to give the title compound as pale yellow oil (0.95 g, 65.00%). The crude product was used for the next step without further purification. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 227.2 (M+1). The resulted mixture was cooled to rt extracted with CH2Cl2 (50 mL×3) The combined organic phases were dried over anhydrous Na2SO4 filtered The filtrate was concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared following the same general protocol as described for rac-((2S,3S)-2-(aminomethyl)-3-methylpiperidin-1-yl)(5-(4-fluorophenyl)-2-methylthiazol-4-yl)methanone in Example A65 using tert-butyl hexahydro-1H-pyrrolo[3,4-b]pyridine-6(2H)-carboxylate. MS (ESI) 346 (M+H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared following the same general protocol as described for rac-((2S,3S)-2-(aminomethyl)-3-methylpiperidin-1-yl)(5-(4-fluorophenyl)-2-methylthiazol-4-yl)methanone in Example A65 using tert-butyl hexahydro-1H-pyrrolo[3,4-b]pyridine-6(2H)-carboxylate. MS (ESI) 346 (M+H).