Data from: A 2nd-generation scalable synthesis of the HIV-1 entry inhibitor CJF-III-288 enabled by photoredox catalysis
Data files
May 04, 2026 version files 19.58 MB
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FID_for_Publication.zip
19.58 MB
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README.md
3.41 KB
Abstract
Herein is reported the development and optimization of a 2nd-Generation process synthesis for the human immunodeficiency virus-1 entry inhibitor CJF-III-288 bis-trifluoroacetate salt 1. The key transformations of the synthesis include a decatungstate-catalyzed diastereoselective Giese addition to set the stereogenecity of the indoline core and install the guanidine motif, followed by a high-yielding photoredox-nickel dual-catalyzed Csp3–Csp2 cross coupling to append the methyl-amino methyl aryl side chain. The route eliminates the use of noble metals, decreases the step count nearly by half, reduces the number of flash column purifications, and increases the overall yield of 1 tenfold. The route has yielded 5.7 grams of 1 for use in in vivo studies.
FID_for_Publication.zip
The folder FID_for_Publication.zip contains all of the raw FID files for the spectra included in the supplementary information. The files are organized into separate folders by compound, and the compounds are numbered the same way they are in the manuscript and supplementary information. The FID files are named by what type of NMR experiment was performed (1H or 13C). For compounds for which variable temperature experiments were performed, there is a separate folder within the compound's folder titled "Variable Temperature Experiments". This folder contains the raw FID files for the variable temperature experiment spectra, separated by nuclei (1H/13C).
Compound Descriptions:
Compound 1
- SMILES:
[NH2-]C(NC[C@H]([C@H]1NC(C(NC2=[C+]C=C(Cl)C(F)=C2)=O)=O)N(C(OCCC)=O)C3=C1C=CC(C[NH2+]C)=C3)=[NH2].[2CF3CO2] - Role: Final product
- Data: ¹H NMR, ¹³C NMR
Compound 7
- SMILES:
BrC1=CC(NC=C2C([H])=O)=C2C=C1 - Role: Intermediate
- Data: ¹H NMR, ¹³C NMR
Compound 8
- SMILES:
BrC1=CC(N(C(OCCC)=O)C=C2C([H])=O)=C2C=C1 - Role: Intermediate
- Data: ¹H NMR, ¹³C NMR
Compound 9
- SMILES:
BrC1=CC(N(C(OCCC)=O)C=C2C(O)=O)=C2C=C1 - Role: Intermediate
- Data: ¹H NMR, ¹³C NMR
Compound 11
- SMILES:
BrC1=CC(N(C(OCCC)=O)C=C2C(N3S(C[C@]4(C5(C)C)[C@@H]3CC5CC4)(=O)=O)=O)=C2C=C1 - Role: Intermediate
- Data: ¹H NMR, ¹³C NMR
Compound 14
- SMILES:
[H]CNC(NC(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O - Role: Reagent
- Data: ¹H NMR, ¹³C NMR
Compound 15
- SMILES:
BrC1=CC(N(C(OCCC)=O)[C@H](CNC(NC(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O)[C@H]2C(N3S(C[C@]4(C5(C)C)[C@@H]3CC5CC4)(=O)=O)=O)=C2C=C1 - Role: Intermediate
- Data: ¹H NMR, ¹³C NMR
Compound 17
- SMILES:
O=C(N1S(C[C@]2(C3(C)C)[C@@H]1CC3CC2)(=O)=O)[C@@H]4[C@@H](CNC(NC(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O)N(C(OCCC)=O)C5=C4C=CC(CN(C)C(OC(C)(C)C)=O)=C5 - Role: Intermediate
- Data: ¹H NMR, ¹³C NMR, Variable Temperature Experiments (1H and 13C)
Compound 20
- SMILES:
CN(CB(F)(F)F)C(OC(C)(C)C)=O.[K] - Role: Reagent
- Data: ¹H NMR, ¹³C NMR
Compound 21
- SMILES:
CN(CC1=CC(N(C(OCCC)=O)[C@H](CNC(NC(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O)[C@H]2N)=C2C=C1)C(OC(C)(C)C)=O - Role: Intermediate
- Data: Crude ¹H NMR
Compound 23
- SMILES:
O=C(NO)[C@@H]1[C@@H](CNC(NC(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O)N(C(OCCC)=O)C2=C1C=CC(CN(C)C(OC(C)(C)C)=O)=C2 - Role: Intermediate
- Data: Crude ¹H NMR
Compound 25
- SMILES:
OC(C(NC1=CC=C(Cl)C(F)=C1)=O)=O - Role: Reagent
- Data: ¹H NMR, ¹³C NMR
Compound 25
- SMILES:
OC(C(NC1=CC=C(Cl)C(F)=C1)=O)=O - Role: Reagent
- Data: ¹H NMR, ¹³C NMR
Compound 26
- SMILES:
O=C(C(NC1=CC=C(Cl)C(F)=C1)=O)N[C@@H]2[C@@H](CNC(NC(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O)N(C(OCCC)=O)C3=C2C=CC(CN(C)C(OC(C)(C)C)=O)=C3 - Role: Intermediate
- Data: ¹H NMR, ¹³C NMR, Variable Temperature Experiments (1H and 13C)
Compound S-4
- SMILES:
CN(CB1OC(C)(C)C(C)(C)O1)C(OC(C)(C)C)=O - Role: Intermediate for Synthesis of Reagent 20
- Data: ¹H NMR, ¹³C NMR, Variable Temperature Experiments (1H and 13C)
Software options for using these FID files to view the NMR spectra include: MestReNova, TopSpin, VNMRJ, NMRPipe, ACD/NMR Processor
Proton (1H) and carbon (13C) NMR spectra were recorded on a Bruker Avance III 500-MHz spectrometer, a Bruker DRX500 500-MHz spectrometer, a Bruker NEO600 600-MHz spectrometer, or a Bruker NEO400 400-MHz spectrometer. Chemical shifts (δ) are reported in parts per million (ppm) relative to methanol (δ 3.31), acetone (δ 2.05), chloroform (δ 7.26), and dimethyl sulfoxide (δ 2.50) for 1H NMR, and methanol (δ 49.15), acetone (δ 29.8), chloroform (δ77.16), and dimethyl sulfoxide (δ39.52) for 13C NMR.