Attaching Fragments into two R-groups (R1 and R2) to get all the combinations?

I would like to attach the fragments db into two R-groups as follows to get all the combinations; I could do for one subtitution/attachment via One-Component Reaction, wondering how can do two subtitution/attachment?

Any thoughts @elsamuel ?

In your post you say you want all the combinations, but you’ve only shown 4 when there should be 16.
Do you really want all? If not, how are you deciding which products you want?

My first thought is to do this enumeration using two sequential reaction nodes.

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yes, all the 16 combinations just gave four for examples.
Btw, when I try Reaction2 of this example it says “WARN RDKit Two Component Reaction 0:30 The following product could not be sanitized and will be skipped:” Is this warning messge is OK?

Also how do i creat the reaction SMARTS? Can’t understand why its [N:1].[#6:2]? Thanks. I have been using something like this for one component: [C:1]Br>>OC(CN(C)[C:1])C1=CCCC=C1

Btw, when I try Reaction2 of this example it says “WARN RDKit Two Component Reaction 0:30 The following product could not be sanitized and will be skipped:” Is this warning messge is OK?

To me, that says there’s something weird happening with the way your molecules are encoded. I get no errors. Can you share your workflow file and data?

Also how do i creat the reaction SMARTS?

The reaction SMARTS I used is [N:1].[#6:2]Br>>[N:1][#6:2]

The period on the left hand side separates the 2 reactants. One reactant has a nitrogen atom which I label as atom 1. The other reagent has a carbon atom that I label as atom 2, and it’s bonded to a bromine atom.

The fragments you gave in your example have both aromatic and aliphatic carbons bonded to the bromine. I can’t use [C:2]Br to encode the reagent because the capital C means aliphatic carbon. I can’t use [c:2]Br because the lowercase c means aromatic carbon. Using the atomic number for carbon [#6] gets around all that.

The right hand side of the equation just says to make a bond between atom 1 and atom 2.