The Nemesis has been successfully synthesised

[edwintse]

The Nemesis is a key compound for the series originally designed to investigate deplanarisation of the RHS group. The synthesis was picked up by Haverford College (#409) with the THP protected alcohol coupling attempted but purification was not attempted due to time constraints (#430). The synthesis was picked up again in the next year with the deprotection successful by NMR/MS (#466). Unfortunately, not enough of the product was isolated for further analysis/biological evaluation.

I have followed the same route outlined in the above attempts, with the exception of the final deprotection step. Instead of the standard THP deprotection conditions (HCl in dioxane), I used standard Boc deprotection conditions (TFA in DCM). I have also made the di-fluorophenyl derivative of the Nemesis outlined below as a comparison.

ELN entries for the condensation reaction, core cyclisation, SN2 displacement (Nemesis/difluoro derivative) and deprotection (Nemesis/difluoro derivative).
ELN entries for the alcohol fragments can be found by following the links in the respective SN2 displacement pages.

The Nemesis 1H,13C,COSY,HSQC,HMBC,LRMS and HRMS (pdfs attached)
The di-fluorophenyl derivative 1H,13C,19F,COSY,HSQC,HMBC,LRMS and HRMS (pdfs attached)

The two compounds will be sent off for biological evaluation in the next batch.

---

Removed from the DCNYS section of the wiki

The Nemesis (deplanarisation of right-hand-side): Haverford College synthetic plan, Start of first Haverford synthesis, ELN, Second phase of synthesis with same ELN.
OC(C1=CC=CC=C1)C OC2=CN=CC3=NN=C(C4CNCCC4)N32
InChI=1S/C18H21N5O2/c24-15(13-5-2-1-3-6-13)12-25-17-11-20-10-16-21-22-18(23(16)17)14-7-4-8-19-9-14/h1-3,5-6,10-11,14-15,19,24H,4,7-9,12H2
SNDLBGDEOQPBOQ-UHFFFAOYSA-N

----------------------------------------------------------------------------------------------------

Strings

The Nemesis
OC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4CNCCC4)N32
InChI=1S/C18H21N5O2/c24-15(13-5-2-1-3-6-13)12-25-17-11-20-10-16-21-22-18(23(16)17)14-7-4-8-19-9-14/h1-3,5-6,10-11,14-15,19,24H,4,7-9,12H2
SNDLBGDEOQPBOQ-UHFFFAOYSA-N

The di-fluorophenyl derivative
FC1=C(F)C=CC(CCOC2=CN=CC3=NN=C(C4CNCCC4)N32)=C1
InChI=1S/C18H19F2N5O/c19-14-4-3-12(8-15(14)20)5-7-26-17-11-22-10-16-23-24-18(25(16)17)13-2-1-6-21-9-13/h3-4,8,10-11,13,21H,1-2,5-7,9H2
DRTAQDBSMNPECX-UHFFFAOYSA-N

[edwintse]

Compound has been removed from the DCNYS section (text copied over above).

[edwintse]

FYI, my next DCNYS target will be the oxazole and oxadiazole.

[edwintse]

PDFs of characterisation uploaded. Closing.