1268524-70-4

Usage

Uses

Used in Pharmaceutical Industry:
(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-triMethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate is used as a therapeutic agent for the treatment of various cancers. Its application is based on its ability to inhibit the BET bromodomain, a protein module involved in cell proliferation and transcriptional regulation. By targeting the BET bromodomain, (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-triMethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate can suppress the growth of cancer cells and potentially treat multiple myeloma and acute myeloid leukemia.
Used in Research Applications:
In the field of research, (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-triMethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate is used as a tool compound to study the role of BET bromodomain proteins in various cellular processes. It is employed in flow cytometry assays, cell viability assays, and quantitative PCR assays to investigate the reversal of HIV-1 latency and the modulation of gene expression.
Used in Drug Delivery Systems:
To enhance the bioavailability and therapeutic outcomes of (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-triMethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate, novel drug delivery systems have been developed. These systems utilize organic and metallic nanoparticles as carriers, aiming to improve the compound's delivery to target cells and tissues, thereby increasing its efficacy against cancer cells.

Biological Activity

(+)-JQ1 is a BET bromodomain inhibitor that acts on BRD4 (2) with C50 being 33nM. Except the BET family, (+)-JQ1 does not bind to the Bromodomain structure domain of other family.

In vitro

(+)-JQ1 enantiomer can bind to directly the Kac binding site of BET bromodomain structure domain. (+)-JQ1 (500nM) and chromatin competitively bind to BRD4, leading to NMC cell differentiation and growth standstill. The Ki67 staining decrease proves that? (+)-JQ1(500nM) weakens the rapid proliferation of NMC 797 and Per403 cell system.????? (+)-JQ1(500nM) acts on NMC 797 cells, effectively reducing the expression of BRD4 target gene. (+)-JQ1acts on NMC11060 cells inhibiting cell activity with IC50 being 4nM. (+)-JQ1 acts on MM cell system and strongly inhibits MYC expression. (+)-JQ1 inhibits the proliferation of KMS-34 and LR5 with IC50 being 68nM and 98nM respectively. After being treated by? (+)-JQ1(500nM), the proportion of MM.1S cell in S phase decrease and more cells stasis in the G0/G1 phase. (+)-JQ1(500nM) dyed by β-galactosidase results in significant cell senescence. In the CD138+-derived MM sample treated by (+)-JQ1(800nM), the cell activity significantly decrease. (+)-JQ1 inhibits LP-1 cell growth with GI50 being 98nM. (+)-JQ1 (625nM) resulted in an increase in the proportion of LP-1 cells at G0/G1 phase. (+)-JQ1 (500nM) acts on LP-1 cells inhibiting MYC, BRD4 and CDK9 expression. (+)-JQ1 (1 μM) deals with latent infection of Jurkat T cells and activates HIV transcription. (+)-JQ1 (50μM) acts on Jurkat and HeLa cells, primarily stimulating Tat-dependent HIV transcription. (+)-JQ1 (5 μM) acts on J-Lat A2 cell inducing Brd4 dissociation, allowing Tat to recruit SEC to the HIV promoter and inducing Pol II CTD phosphorylation and viral transcription.

In vivo

(+)-JQ1(50mg /kg) treats mice with NMC797 transplanted tumors inhibiting tumor growth. (+)-JQ1(50mg/kg) erases NUT nuclear spots in mice with NMC797 transplanted tumors, consistent with competitive binding to nuclear chromatin. (+)-JQ1 (50mg/kg) treats NMC797 transplanted tumor, significantly inducing (31grade) keratin expression. (+)-JQ1(50mg/kg) treats mouse model carrying NMC transplanted tumor, promoting differentiation, tumor decline and prolonging life. (+)-JQ1(50mg/kg) treats MM.1S-luc+ cells through intravenous injection. Compared with animals in control group, the life of SCID beige mice carrying orthotopic transplanted tumors significantly extends. Through intraperitoneal injection (+)-JQ1(50mg/kg) can prolong the life of mice carrying Raji xenograft greatly.

Characteristic

(+)-JQ1 is more effective than (-)-JQ1.

Biochem/physiol Actions

(+)-JQ1 is a high affinity, potent and selective inhibitor of BET bromodomain proteins, including BRD2, BRD3, BRD4 and BRDT. (+)-JQ1 (also known as SGCBD01), the active enantiomer of (+/-)-JQ1, inhibits Brd4 (bromodomain-containing 4), which forms complexes with chromatin via two tandem bromodomains (BD1 and BD2) that bind to acetylated lysine residues in histones and Brd4 association with acetylated chromatin is believed to regulate the recruitment of elongation factor b and additional transcription factors to specific promoter regions. The nuclear protein in testis (NUT) gene is known to form fusions with Brd4 that create a potent oncogene, leading to rare, but highly lethal tumors referred to as NUT midline carcinomas (NMC). (+)-JQ1 inhibits recruitment and binding of Brd4 to TNFa and E-selectin promoter elements, and accelerates recovery time in FRAP (fluorescence recovery after photobleaching) assays using GFP-Brd4. Thus (+)-JQ1 is a useful tool to study the role of Brd4 in transcriptional initiation.For characterization details of (+)-JQ1, please visit the JQ-1 probe summary on the Structural Genomics Consortium (SGC) website.(-)-JQ1 is the negative control for the active enantiomer, (+)-JQ1. (-)-JQ1 is available from Sigma. To learn more about and purchase (-)-JQ1, click here.To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc

References

References/Citations:

Synthetic route

(S)-tert-butyl 2-(5-(4-chlorophenyl)-6,7-dimethyl-2-oxo-2,3-dihydro-1H-thieno[2,3-e][1,4]diazepin-3-yl)acetate (1268524-67-9) + acetic acid hydrazide (1068-57-1) → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Stage #1: tert-butyl (S)-2-(5-(4-chlorophenyl)-6,7-dimethyl-2-oxo-2,3-dihydro-1H-thieno[2,3-e][1,4]diazepin-3-yl)acetate With potassium tert-butylate In tetrahydrofuran at -78 - 23℃; for 0.5h; Stage #2: With diethyl chlorophosphate In tetrahydrofuran at -10℃; for 0.75h; Stage #3: acetic acid hydrazide In tetrahydrofuran; butan-1-ol at 23 - 90℃; for 2h;	92%
Stage #1: tert-butyl (S)-2-(5-(4-chlorophenyl)-6,7-dimethyl-2-oxo-2,3-dihydro-1H-thieno[2,3-e][1,4]diazepin-3-yl)acetate With potassium tert-butylate In tetrahydrofuran at -78 - -10℃; for 0.5h; Stage #2: With chlorophosphoric acid diphenyl ester In tetrahydrofuran at -78 - -40℃; for 0.75h; Stage #3: acetic acid hydrazide Further stages;	60.2%
With potassium tert-butylate; diethyl chlorophosphate In tetrahydrofuran
Stage #1: tert-butyl (S)-2-(5-(4-chlorophenyl)-6,7-dimethyl-2-oxo-2,3-dihydro-1H-thieno[2,3-e][1,4]diazepin-3-yl)acetate In tetrahydrofuran; toluene at -40℃; for 1h; Stage #2: With chlorophosphoric acid diphenyl ester In tetrahydrofuran; toluene at -10℃; for 2.3h; Stage #3: acetic acid hydrazide In tetrahydrofuran; toluene at 20 - 80℃; for 2.5h; Reagent/catalyst; Temperature; Solvent;

Trimethyl orthoacetate (1445-45-0) + C21H23ClN2O2S2 → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Stage #1: C21H23ClN2O2S2 With hydrazine hydrate In tetrahydrofuran at 23℃; for 1h; Stage #2: Trimethyl orthoacetate In toluene at 120℃; for 2h;	85%

(2-amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanone (50508-66-2) → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: N-ethyl-N,N-diisopropylamine; 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) / N,N-dimethyl-formamide / 16 h / 23 °C 2.1: piperidine / N,N-dimethyl-formamide / 0.5 h / 23 °C 3.1: silica gel / ethanol / 3 h / 90 °C 4.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / -78 - 23 °C 4.2: 0.75 h / -10 °C 4.3: 2 h / 23 - 90 °C View Scheme
Multi-step reaction with 4 steps 1.1: N-ethyl-N,N-diisopropylamine; 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) / N,N-dimethyl-formamide / 16 h / 23 °C 2.1: piperidine / N,N-dimethyl-formamide / 0.5 h / 23 °C 3.1: silica gel / ethanol / 3 h / 90 °C 4.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / -78 - 23 °C 4.2: 0.75 h / -10 °C 4.3: 2 h / 23 - 90 °C View Scheme
Multi-step reaction with 5 steps 1.1: 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V); N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.08 h / 23 °C 1.2: 16 h / 23 °C 2.1: piperidine / N,N-dimethyl-formamide / 0.5 h / 23 °C 3.1: acetic acid / ethanol / 0.5 h / 85 °C 4.1: tetraphosphorus decasulfide; sodium hydrogencarbonate / tetrahydrofuran / 16 h / 90 °C 5.1: hydrazine hydrate / tetrahydrofuran / 1 h / 23 °C 5.2: 2 h / 120 °C View Scheme

p-chlorobenzoylacetonitrile (4640-66-8) → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: morpholine; sulfur / ethanol / 12 h / 23 - 70 °C 2.1: N-ethyl-N,N-diisopropylamine; 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) / N,N-dimethyl-formamide / 16 h / 23 °C 3.1: piperidine / N,N-dimethyl-formamide / 0.5 h / 23 °C 4.1: silica gel / ethanol / 3 h / 90 °C 5.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / -78 - 23 °C 5.2: 0.75 h / -10 °C 5.3: 2 h / 23 - 90 °C View Scheme
Multi-step reaction with 5 steps 1.1: morpholine; sulfur / ethanol / 12 h / 23 - 70 °C 2.1: N-ethyl-N,N-diisopropylamine; 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) / N,N-dimethyl-formamide / 16 h / 23 °C 3.1: piperidine / N,N-dimethyl-formamide / 0.5 h / 23 °C 4.1: silica gel / ethanol / 3 h / 90 °C 5.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / -78 - 23 °C 5.2: 0.75 h / -10 °C 5.3: 2 h / 23 - 90 °C View Scheme
Multi-step reaction with 6 steps 1.1: morpholine; sulfur / ethanol / 12 h / 25 °C 2.1: 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V); N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.08 h / 23 °C 2.2: 16 h / 23 °C 3.1: piperidine / N,N-dimethyl-formamide / 0.5 h / 23 °C 4.1: acetic acid / ethanol / 0.5 h / 85 °C 5.1: tetraphosphorus decasulfide; sodium hydrogencarbonate / tetrahydrofuran / 16 h / 90 °C 6.1: hydrazine hydrate / tetrahydrofuran / 1 h / 23 °C 6.2: 2 h / 120 °C View Scheme

(S)-tert-butyl-3-amino-4-((3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-yl)amino)-4-oxobutanoate (1268524-66-8) → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: silica gel / ethanol / 3 h / 90 °C 2.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / -78 - 23 °C 2.2: 0.75 h / -10 °C 2.3: 2 h / 23 - 90 °C View Scheme
Multi-step reaction with 3 steps 1.1: acetic acid / ethanol / 0.5 h / 85 °C 2.1: tetraphosphorus decasulfide; sodium hydrogencarbonate / tetrahydrofuran / 16 h / 90 °C 3.1: hydrazine hydrate / tetrahydrofuran / 1 h / 23 °C 3.2: 2 h / 120 °C View Scheme
Multi-step reaction with 2 steps 1: silica gel / toluene 2: potassium tert-butylate; diethyl chlorophosphate / tetrahydrofuran View Scheme

tert-butyl-3-amino-4-((3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-yl)amino)-4-oxobutanoate → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: acetic acid / ethanol / 0.5 h / 85 °C 2.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / -78 - 23 °C 2.2: 0.75 h / -10 °C 2.3: 2 h / 23 - 90 °C View Scheme

(S)-tert-butyl 2-(5-(4-chlorophenyl)-6,7-dimethyl-2-oxo-2,3-dihydro-1H-thieno[2,3-e][1,4]diazepin-3-yl)acetate (1268524-67-9) → (-)-JQ1 (1268524-71-5) + (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / -78 - -10 °C 1.2: 0.75 h / -78 - -10 °C 2.1: tetrahydrofuran; butan-1-ol / 2 h / 20 - 90 °C View Scheme

(R)-tert-butyl 2-(5-(4-chlorophenyl)-6,7-dimethyl-2-oxo-2,3-dihydro-1H-thieno[2,3-e][1,4]diazepin-3-yl)acetate → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: tetraphosphorus decasulfide; sodium hydrogencarbonate / tetrahydrofuran / 16 h / 90 °C 2.1: hydrazine hydrate / tetrahydrofuran / 1 h / 23 °C 2.2: 2 h / 120 °C View Scheme

para-Chlorobenzyl alcohol (873-76-7) → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: copper dichloride; potassium hydroxide; oxygen / N,N-dimethyl acetamide / 12 h / 25 °C 2.1: morpholine; sulfur / ethanol / 12 h / 25 °C 3.1: 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V); N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.08 h / 23 °C 3.2: 16 h / 23 °C 4.1: piperidine / N,N-dimethyl-formamide / 0.5 h / 23 °C 5.1: acetic acid / ethanol / 0.5 h / 85 °C 6.1: tetraphosphorus decasulfide; sodium hydrogencarbonate / tetrahydrofuran / 16 h / 90 °C 7.1: hydrazine hydrate / tetrahydrofuran / 1 h / 23 °C 7.2: 2 h / 120 °C View Scheme

C9H7NOS → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: morpholine; sulfur / ethanol 2: benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide 3: piperidine / N,N-dimethyl-formamide 4: silica gel / toluene 5: potassium tert-butylate; diethyl chlorophosphate / tetrahydrofuran View Scheme

Fmoc-(tBu)Asp-OH (71989-14-5) → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide 2: piperidine / N,N-dimethyl-formamide 3: silica gel / toluene 4: potassium tert-butylate; diethyl chlorophosphate / tetrahydrofuran View Scheme

tert-butyl (3S)-3-amino-4-[[3-(4-chlorobenzoyl)-4,5-dimethyl-2-thienyl]amino]-4-oxobutanoate tosylate salt → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / Isopropyl acetate; water / 2 h / 25 °C 2.1: potassium amylate / tetrahydrofuran; toluene / 1 h / -40 °C 2.2: 2.3 h / -10 °C 2.3: 2.5 h / 20 - 80 °C View Scheme

tert-butyl 3-amino-4-[[3-(4-chlorobenzoyl)-4,5-dimethyl-2-thienyl]amino]-4-oxobutanoate tosylate salt → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / Isopropyl acetate; water / 2 h / 25 °C 2.1: potassium amylate / tetrahydrofuran; toluene / 1 h / -40 °C 2.2: 2.3 h / -10 °C 2.3: 2.5 h / 20 - 80 °C View Scheme

4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine (166880-01-9) + bromoacetic acid tert-butyl ester (5292-43-3) → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Stage #1: 4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine With lithium hexamethyldisilazane In tetrahydrofuran at -70℃; for 1h; Stage #2: bromoacetic acid tert-butyl ester In tetrahydrofuran at -70 - 20℃; for 5h;

C15H13Cl2NO2S (204587-29-1) → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: sodium iodide / tetrahydrofuran / 2 h / 60 °C 2.1: ammonia / tetrahydrofuran / 3.5 h / -60 - 20 °C 3.1: acetic acid / isopropyl alcohol / 3 h / 90 °C 4.1: tetraphosphorus decasulfide; sodium carbonate / 1,2-dichloro-ethane / 5 h / 65 °C 5.1: hydrazine hydrate / methanol / 1 h / 0 °C 6.1: toluene / 1 h / 80 °C 7.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -70 °C 7.2: 5 h / -70 - 20 °C View Scheme

C15H13ClINO2S → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: ammonia / tetrahydrofuran / 3.5 h / -60 - 20 °C 2.1: acetic acid / isopropyl alcohol / 3 h / 90 °C 3.1: tetraphosphorus decasulfide; sodium carbonate / 1,2-dichloro-ethane / 5 h / 65 °C 4.1: hydrazine hydrate / methanol / 1 h / 0 °C 5.1: toluene / 1 h / 80 °C 6.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -70 °C 6.2: 5 h / -70 - 20 °C View Scheme

glycine 3-(4-chloro-benzoyl)-4,5-dimethyl-thiophen-2-ylamide (54861-99-3) → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: acetic acid / isopropyl alcohol / 3 h / 90 °C 2.1: tetraphosphorus decasulfide; sodium carbonate / 1,2-dichloro-ethane / 5 h / 65 °C 3.1: hydrazine hydrate / methanol / 1 h / 0 °C 4.1: toluene / 1 h / 80 °C 5.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -70 °C 5.2: 5 h / -70 - 20 °C View Scheme

5-(4-chloro-phenyl)-6,7-dimethyl-1,3-dihydro-thieno[2,3-e][1,4]diazepin-2-one (33671-41-9) → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: tetraphosphorus decasulfide; sodium carbonate / 1,2-dichloro-ethane / 5 h / 65 °C 2.1: hydrazine hydrate / methanol / 1 h / 0 °C 3.1: toluene / 1 h / 80 °C 4.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -70 °C 4.2: 5 h / -70 - 20 °C View Scheme

C15H13ClN2S2 → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrazine hydrate / methanol / 1 h / 0 °C 2.1: toluene / 1 h / 80 °C 3.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -70 °C 3.2: 5 h / -70 - 20 °C View Scheme

C15H15ClN4S → (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: toluene / 1 h / 80 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -70 °C 2.2: 5 h / -70 - 20 °C View Scheme

(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) → (S)-[4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetic acid

Conditions	Yield
With formic acid at 20℃; for 75h;	100%
With formic acid at 20℃; for 75h;	100%
With trifluoroacetic acid In dichloromethane at 20℃; for 5h;	100%

(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) + trifluoroacetic acid (76-05-1) → 2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetraazatricyclo[8.3.0.02’6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetic acid trifluoroacetic acid salt

Conditions	Yield
In dichloromethane at 20℃; for 2h;	100%
In dichloromethane at 20℃; for 3h;	100%

(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) + chloroacetyl chloride (79-04-9) → (S)-[4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetic acid

Conditions	Yield
With formic acid at 45℃;	99.8%

3-phthalimido-1-propene (5428-09-1) + (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) → C34H33N5O4S

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); N-Methyldicyclohexylamine; tri tert-butylphosphoniumtetrafluoroborate In 1-methyl-pyrrolidin-2-one at 160℃; for 0.333333h; Microwave irradiation;	99.2%

Benzophenone imine (1013-88-3) + (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) → tert-butyl (S)-2-(4-(4-((diphenylmethylene)amino)phenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate

Conditions	Yield
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate In toluene at 110℃; for 16h; Inert atmosphere;	98.5%
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate In toluene at 110℃; for 16h; Inert atmosphere;	60%
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate In toluene at 110℃; for 16h; Inert atmosphere;	60%

methanol (67-56-1) + (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) → methyl 2-((6S,Z)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f] [1,2,4]triazolo[4,3-a] [1,4]diazepin-6-yl)acetate (916489-36-6)

Conditions	Yield
With sulfuric acid Reflux;	95%

(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) + tert-Butyldimethyl(prop-2-ynyloxy)silane (76782-82-6) → tert-butyl (S)-2-(4-(4-(3-((tert-butyldimethylsilyl)oxy)prop-1-yn-1-yl)phenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate

Conditions	Yield
With bis[dicyclohexyl(2,4,6-triisopropyl-[1,1':3',1''-terphenyl]-2-yl)phosphane]palladium(II) dichloride; caesium carbonate In acetonitrile at 100℃; for 1.5h; Inert atmosphere;	70%

trifluoromethylsulfonic anhydride (358-23-6) + (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) + C18H27N3O7 → C41H51ClN7O8S(1+)*CF3O3S(1-)

Conditions	Yield
Stage #1: trifluoromethylsulfonic anhydride; C18H27N3O7 With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at -78℃; for 0.833333h; Inert atmosphere; Stage #2: (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate In tetrahydrofuran at -78℃; for 1.33333h; Inert atmosphere;	52%

N-methylpropargylamine (35161-71-8) + (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) → tert-butyl (S)-2-(2,3,9-trimethyl-4-(4-(3-(methylamino)prop-1-yn-1-yl)phenyl)-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate

Conditions	Yield
With bis[dicyclohexyl(2,4,6-triisopropyl-[1,1':3',1''-terphenyl]-2-yl)phosphane]palladium(II) dichloride; caesium carbonate In acetonitrile at 90℃; for 1h; Microwave irradiation;	50%

trifluoromethylsulfonic anhydride (358-23-6) + (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) + C13H17N3O3 → C36H41ClN7O4S(1+)*CF3O3S(1-)

Conditions	Yield
Stage #1: trifluoromethylsulfonic anhydride; C13H17N3O3 With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at -78℃; for 0.833333h; Inert atmosphere; Stage #2: (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate In tetrahydrofuran at -78℃; for 1.33333h; Inert atmosphere;	43%

trifluoromethylsulfonic anhydride (358-23-6) + (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) + C14H19N3O4 → C37H43ClN7O5S(1+)*CF3O3S(1-)

Conditions	Yield
Stage #1: trifluoromethylsulfonic anhydride; C14H19N3O4 With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at -78℃; for 0.833333h; Inert atmosphere; Stage #2: (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate In tetrahydrofuran at -78℃; for 1.33333h; Inert atmosphere;	40%

(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) + 1,1-dimethylprop-3-ynylamine (2978-58-7) → tert-butyl (S)-2-(4-(4-(3-amino-3-methylbut-1-yn-1-yl)phenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate

Conditions	Yield
With bis[dicyclohexyl(2,4,6-triisopropyl-[1,1':3',1''-terphenyl]-2-yl)phosphane]palladium(II) dichloride; caesium carbonate In acetonitrile at 95℃; for 1.5h; Microwave irradiation;	38%

(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) + but-3-yn-2-amine (30389-17-4) → tert-butyl 2-((6S)-4-(4-(3-aminobut-1-yn-1-yl)phenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate

Conditions	Yield
With bis[dicyclohexyl(2,4,6-triisopropyl-[1,1':3',1''-terphenyl]-2-yl)phosphane]palladium(II) dichloride; caesium carbonate In acetonitrile at 95℃; for 1.5h; Microwave irradiation;	32%

(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) + Propargylamine (2450-71-7) → tert-butyl (S)-2-(4-(4-(3-aminoprop-1-yn-1-yl)phenyl)-2,3,9-trimethyl-6H-thieno[3,2-f ][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate

Conditions	Yield
With Pd(Cy*Phine)2Cl2 ; caesium carbonate In N,N-dimethyl-formamide at 120℃; for 1h; Microwave irradiation; Inert atmosphere;	24%

(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) + but-3-yn-1-amine (14044-63-4) → tert-butyl (S)-2-(4-(4-(4-aminobut-1-yn-1-yl)phenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate

Conditions	Yield
With bis[dicyclohexyl(2,4,6-triisopropyl-[1,1':3',1''-terphenyl]-2-yl)phosphane]palladium(II) dichloride; caesium carbonate In acetonitrile at 90℃; for 2h; Microwave irradiation;	10%

(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) + C26H24N2O6S → (+)-JQ1

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; Inert atmosphere;
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃;

(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) → 8-{2-[(S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetyl}-8-azabicyclo[3.2.1]octan-3-one (1426257-53-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / 1,4-dioxane / 20 °C 2: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 3 h / 20 °C View Scheme

(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) → 2-[(S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-1-(2-oxa-6-azaspiro[3.3]hept-6-yl)ethan-1-one (1426257-54-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / 1,4-dioxane / 20 °C 2: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 2 h / 20 °C View Scheme

(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) → (1R,5S)-tert-butyl 3-({2-[(S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetyl}amino)-9-azabicyclo[3.3.1]nonane-9-carboxylate

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / 1,4-dioxane / 20 °C 2: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 16 h / 20 °C View Scheme

(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) → N-[(1R,5S)-9-azabicyclo[3.3.1]non-3-yl]-2-[(S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetamide

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogenchloride / 1,4-dioxane / 20 °C 2: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 16 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 20 °C View Scheme

(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) → 2-[(S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-1-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)ethan-1-one (1426257-55-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / 1,4-dioxane / 20 °C 2: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 20 °C View Scheme

(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) → 2-[(S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-1-(2-oxa-6-azaspiro[3.4]oct-6-yl)ethan-1-one (1426257-56-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / 1,4-dioxane / 20 °C 2: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 20 °C View Scheme

(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (1268524-70-4) → 2-[(S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-1-(2-oxa-7-azaspiro[3.5]non-6-yl)ethan-1-one (1426257-57-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / 1,4-dioxane / 20 °C 2: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 20 °C View Scheme

Upstream product

• 1268524-67-9 tert-butyl (S)-2-(5-(4-chlorophenyl)-6,7-dimethyl-2-oxo-2,3-dihydro-1H-thieno[2,3-e][1,4]diazepin-3-yl)acetate 
• 1068-57-1 acetic acid hydrazide 
• 50508-66-2 (2-amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanone 
• 4640-66-8 p-chlorobenzoylacetonitrile 
• 1268524-66-8 (S)-tert-butyl-3-amino-4-((3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-yl)amino)-4-oxobutanoate 
• 1268524-65-7 (S)-tert-butyl 3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-((3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-yl)amino)-4-oxobutanoate 
• 1445-45-0 Trimethyl orthoacetate 
• 873-76-7 para-Chlorobenzyl alcohol 
• 108-22-5 Isopropenyl acetate 
• 64-17-5 ethanol 
• 122-51-0 orthoformic acid triethyl ester 
• 67-64-1 acetone 
• 78-10-4 tetraethoxy orthosilicate 
• 16694-46-5 ethyl formimidate hydrochloride 

Downstream Products

• 1426257-53-5 8-{2-[(S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetyl}-8-azabicyclo[3.2.1]octan-3-one 
• 1426257-54-6 2-[(S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-1-(2-oxa-6-azaspiro[3.3]hept-6-yl)ethan-1-one 
• 1426257-55-7 2-[(S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-1-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)ethan-1-one 
• 1426257-56-8 2-[(S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-1-(2-oxa-6-azaspiro[3.4]oct-6-yl)ethan-1-one 
• 1426257-57-9 2-[(S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-1-(2-oxa-7-azaspiro[3.5]non-6-yl)ethan-1-one 
• 1426257-58-0 (S)-1-(2-azabicyclo[2,2,2]oct-2-yl)-2-[(6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]ethanone 
• 1426257-60-4 (S)-6-(carboxymethyl)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine hydrochloride 
• 202592-23-2 (S)-[4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetic acid 

Relevant academic research and scientific papers

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