Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.
Procedure: A solution of ethyl 2-((2-aminoethyl)thio)acetate (intermediate 210, 675 mg, 2.87 mmol) in DMA (7.5 ml) and MeOH (7.5 ml) was added to a solution of 2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridine-3-carbaldehyde (intermediate 41, 710 mg, 3.01 mmol) and Et3N (0.417 mL, 3.01 mmol) in MeOH (7.5 ml) and the reaction mixture was stirred at room temperature for 3 days. NaBH4 (142 mg, 3.75 mmol) was added portion wise and stirring was continued for 40 min at room temperature. Additional Et3N (500 μL, 3.61 mmol) was added and mixture was stirred for 4 h. Solvents were concentrated and the residue was partitioned between DCM and aqueous citric acid (5%). The aqueous layer was extracted with DCM (3×) and the combined organic layers were washed with aqueous citric acid (5%) (3×). The pH value of the combined water layers was adjusted to 9 using aqueous Na2CO3 and the water phase was back extracted with DCM (3×). The organic layers were combined, dried using Na2SO4, filtered and evaporated to yield the title compound as an orange oil. (UPLC-MS 3) tR 0.61 min; ESI-MS 384.1 [M+H]+. 1H NMR (600 MHz, DMSO-d6) δ 7.16 (s, 1H), 6.40-6.36 (m, 1H), 5.08 (s, 1H), 4.12-4.05 (m, 2H), 3.61 (s, 2H), 3.36-3.21 (m, 10H), 2.71-2.61 (m, 6H), 1.80-1.72 (m, 2H), 1.19 (t, 3H
stirring
was continued for 40 min at room temperature
mixture was stirred for 4 h
Solvents were concentrated
the residue was partitioned between DCM and aqueous citric acid (5%)
The aqueous layer was extracted with DCM (3×)
the combined organic layers were washed with aqueous citric acid (5%) (3×)
the water phase was back extracted with DCM (3×)
dried
filtered
evaporated
Source ID: ord-e244e95ca9b747bbabde038c7d34db1f