JH-II-127

Base Information

• Chemical Name: JH-II-127
• CAS No.: 1700693-08-8
• Molecular Formula: C₁₉H₂₁ClN₆O₃
• Molecular Weight: 416.867
• Mol file: 1700693-08-8.mol

Synonyms:JH-II-127

Chemical Property of JH-II-127

Chemical Property:

• PKA: 12.49±0.50(Predicted)
• PSA: 104.40000
• Density: 1.458±0.06 g/cm3(Predicted)
• LogP: 2.96150
• Storage Temp.: Refrigerator
• Solubility.: DMSO (Slightly), Methanol (Slightly)

Purity/Quality:

97% ^*data from raw suppliers

JH-II-127 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Description: JH-II-127 is an orally bioavailable inhibitor of wild-type (WT) and mutant forms of leucine-rich repeat kinase 2 (LRRK2). It inhibits WT LRRK2, as well as LRRK2 containing the G2019S and A2016T substitution mutations (IC50s = 6.6, 2.2, and 47.7 nM, respectively), which are present in certain patients with Parkinson’s disease, but not LRRK2 containing both mutations (IC50 = 3,080 nM). JH-II-127 (0.1-0.3 μM) inhibits phosphorylation of the serines at positions 910 and 935 of WT LRRK2 and LRRK2G2019S in vitro. It also inhibits Ser935 phosphorylation in vivo in mouse brain, spleen, and kidney when administered at a dose of 30 mg/kg.
• Uses: JH-II-127 is a highly potent, selective, and brain penetrant LRRK2 inhibitor.

Technology Process of JH-II-127

There total 9 articles about JH-II-127 which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 68.0%

C25H35ClN6O4Si → [4-[[5-chloro-4-(methylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxyphenyl]-4-morpholinylmethanone (1700693-08-8)

Guidance literature:

C₂₅H₃₅ClN₆O₄Si; With trifluoroacetic acid; In dichloromethane; at 50 ℃; for 3h;

With sodium hydrogencarbonate; In tetrahydrofuran; water; for 6h;

DOI:10.1021/acsmedchemlett.5b00064

Reference yield: 58.0%

(4-amino-3-methoxyphenyl)(morpholino)methanone + 2,5-dichloro-N-methyl-7-((2-(trimethyl silyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine → [4-[[5-chloro-4-(methylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxyphenyl]-4-morpholinylmethanone (1700693-08-8)

Guidance literature:

With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; potassium carbonate; XPhos; In iso-butanol; at 90 ℃; for 6h;

Reference yield:

2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (90213-66-4) → [4-[[5-chloro-4-(methylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxyphenyl]-4-morpholinylmethanone (1700693-08-8)

Guidance literature:

Multi-step reaction with 5 steps

1.1: N-chloro-succinimide / dichloromethane; tetrahydrofuran / 2.5 h / 90 °C / Microwave irradiation

2.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 °C

2.2: 3 h / 20 °C

3.1: methanol / 1 h / 70 °C

4.1: potassium carbonate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; XPhos / iso-butanol / 6 h / 90 °C / Inert atmosphere

5.1: trifluoroacetic acid / dichloromethane / 3 h / 50 °C

5.2: 6 h

With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; N-chloro-succinimide; sodium hydride; potassium carbonate; trifluoroacetic acid; XPhos; In tetrahydrofuran; methanol; dichloromethane; N,N-dimethyl-formamide; iso-butanol; 4.1: |Buchwald-Hartwig Coupling;

DOI:10.1021/acsmedchemlett.5b00064

upstream raw materials:

pyrrolo<2,3-d>pyrimidin-2,4-dione

2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine

2,4,5-trichloro-7H-pyrrolo [2,3-d] pyrimidine

2,4,5-trichloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine