Abstract: Methods and systems provide proposed pathways for synthesizing chemical reactions given a user-proposed target molecule, user-provided reaction constraints, or a combination of both. Embodiments may leverage training the model using both known successful reactions and infeasible reactions, either known or created by a prior use of the model. Chemical reactions for producing the target molecule and substrates are proposed using the model. From the proposed reactions, synthesis pathways are extracted and ranked according to a cost estimation. The ranked synthesis pathways are then provided to the user.