| Identification | Back Directory | [Name]
N-Tosyl-5-bromo-4,7-diazaindole | [CAS]
1201186-54-0 | [Synonyms]
N-Tosyl-5-bromo-4,7-diazaindole
2-BroMo-5-tosyl-5H-pyrrolo[2,3-b]pyrazine
2-BROMO-5-(P-TOLYLSULFONYL)-5H-PYRROLO[2,3-B]PYRAZINE
2-bromo-5-(4-methylphenyl)sulfonylpyrrolo[2,3-b]pyrazine
2-bromo-5-(4-methylbenzenesulfonyl)-5H-pyrrolo[2,3-b]pyrazine
2-Bromo-5-[(4-methylphenyl)sulfonyl]-5H-pyrrolo[2,3-b]pyrazine
5H-Pyrrolo[2,3-b]pyrazine, 2-bromo-5-[(4-methylphenyl)sulfonyl]- | [Molecular Formula]
C13H10BrN3O2S | [MDL Number]
MFCD12964053 | [MOL File]
1201186-54-0.mol | [Molecular Weight]
352.21 |
| Chemical Properties | Back Directory | [Boiling point ]
499.6±55.0 °C(Predicted) | [density ]
1.68±0.1 g/cm3(Predicted) | [storage temp. ]
Inert atmosphere,2-8°C | [pka]
-2.22±0.30(Predicted) | [Appearance]
Light brown to brown Solid | [InChI]
InChI=1S/C13H10BrN3O2S/c1-9-2-4-10(5-3-9)20(18,19)17-7-6-11-13(17)15-8-12(14)16-11/h2-8H,1H3 | [InChIKey]
UMZKBENCNNDLRF-UHFFFAOYSA-N | [SMILES]
C12N(S(C3=CC=C(C)C=C3)(=O)=O)C=CC1=NC(Br)=CN=2 |
| Hazard Information | Back Directory | [Uses]
N-Tosyl-5-bromo-4,7-diazaindole is an intermediate of upadacitinib, known asupadacitinib intermediate, or upadacitinib impurity 2. As an inhibitor of Janus kinase1, upadacitinib selectively inhibits Janus kinase1 for immune system diseases such as psoriatic arthritis, rheumatoid arthritis, and Crohn's disease[1-3].
Referances:
[1] Yael Ross, Marina Magrey, Use of upadacitinib in the treatment of psoriatic arthritis, Immunotherapy, 2021, 13.
[2] Lina Serhal, Christopher J Edwards, Upadacitinib for the treatment of rheumatoid arthritis, Expert Review of Clinical Immunology, 2018, 15,13-25.
[3] Eleni Kotsiliti, Upadacitinib therapy for Crohn’s disease, Nature Reviews Gastroenterology & Hepatology, 2023, 20, 483. | [Preparation]
A solution of anhydrous DMF (272 mL) dissolved with 2-bromo-5H-pyrrolo[2,3-b]pyrazine (78.0 g, 394 mmol) was configured. The temperature is maintained at 0-5 °C (within which the subsequent reaction has been maintained), and the solution was droppedly added to the sodium (12.8 g, 532 mmol) anhydrous DMF (543 mL) suspension in the stirred state within 60 minutes. The solution turned brown and the reaction solution was stirred for about 30 min. Then, within 60 minutes, anhydrous DMF (272 mL) dissolved with p-toluenesulfonyl chloride (94.0 g, 492 mmol) was added. After stirring the mixed solution for about 1 h, it was heated to ambient temperature and stirred for about 18 h. Slowly pour the reaction mixture into ice water (6 L) and added 2.5 N NaOH in water (50.0 mL, 125 mmol). Filter the sediment to collect and stirred 3 times with cold water (200 mL). Finally, the collected products were filtered and dried to a constant weight in a vacuum oven at about 55 °C to obtain N-Tosyl-5-bromo-4,7-diazaindole (134.6 g, 97%). | [Safety]
N-Tosyl-5-bromo-4,7-diazaindole can cause skin irritation, severe eye irritation, and possibly respiratory irritation. | [Synthesis]
To a solution of 5-bromo-3-[(trimethylsilyl)alkynyl]pyrazin-2-amine (3.00 g, 11.1 mmol) in DMF (60 mL) was added NaH (60% dispersed in mineral oil, 0.577 g, 14.4 mmol) in batches at 0 °C. After 15 min of reaction, p-toluenesulfonyl chloride (2.75 g, 14.4 mmol) was added, followed by slow warming of the reaction system to room temperature. After 16 hours of reaction, the mixture was poured into ice water (120 mL) and the precipitate was collected by vacuum filtration. The crude product was dissolved in DCM (15 mL) and purified by silica gel column chromatography, using DCM as eluent. The fractions containing the target product were combined and concentrated under reduced pressure to afford 2-bromo-5-toluenesulfonyl-5H-pyrrolo[2,3-b]pyrazine (2.16 g, 52% yield).LC/MS analysis (see Table 2 for conditions, method d) showed: retention time Rt = 1.58 min; mass spectrum m/z: 352/354 (M+H)+. | [References]
[1] Yael Ross, Marina Magrey, Use of upadacitinib in the treatment of psoriatic arthritis, Immunotherapy, 2021, 13.
[2] Lina Serhal, Christopher J Edwards, Upadacitinib for the treatment of rheumatoid arthritis, Expert Review of Clinical Immunology, 2018, 15,13-25.
[3] Eleni Kotsiliti, Upadacitinib therapy for Crohn’s disease, Nature Reviews Gastroenterology & Hepatology, 2023, 20, 483. |
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| Company Name: |
Tetranov Biopharm
|
| Telephone: |
13526569071 |
| Website: |
http://www.leadmedpharm.com/index.html |
| Company Name: |
Adamas Reagent, Ltd.
|
| Telephone: |
4006009262 13023226327 |
| Website: |
http://www.tansoole.com |
|