Jennifer Lawrence was attached to star in the project, to be directed by "Boyhood" helmer Richard Linklater, but left last fall when her schedule became overstuffed, said The Hollywood Reporter.
The producers - Matt Tolmach and Michael Costigan - and studio vowed to rebuild, and now they are closing on 39-year-old Reynolds, who post-"Deadpool" is in demand as he enjoys a career resurgence.
"Rosie Project" tells the story of a socially inept genetics professor who comes up with a scientifically sound survey to find the perfect mate.
The film is an adaptation of the book by Graeme Simsion and has a script by Scott Neustadter and Michael Weber.