(R)-2-fluoro-10a-methyl-7,8,9,10,10a,11-hexahydro-5,6,7a,11-tetraazacyclohepta[def]cyclopenta[a]fluoren-4(5H)-one

Base Information

• Chemical Name: (R)-2-fluoro-10a-methyl-7,8,9,10,10a,11-hexahydro-5,6,7a,11-tetraazacyclohepta[def]cyclopenta[a]fluoren-4(5H)-one
• CAS No.: 1446261-44-4
• Molecular Formula: C16H15FN4O
• Molecular Weight: 298.31
• Mol file: 1446261-44-4.mol

Synonyms:(R)-2-fluoro-10a-methyl-7,8,9,10,10a,11-hexahydro-5,6,7a,11-tetraazacyclohepta[def]cyclopenta[a]fluoren-4(5H)-one;(R)-2-fluoro-10a-methyl-5,8,9,10,10a,11-hexahydro-5,6,7a,11-tetraazacyclohepta[def]cyclopenta[a]fluoren-4(7H)-one;bgb-290

Chemical Property of (R)-2-fluoro-10a-methyl-7,8,9,10,10a,11-hexahydro-5,6,7a,11-tetraazacyclohepta[def]cyclopenta[a]fluoren-4(5H)-one

Chemical Property:

• PKA: 11.56±0.40(Predicted)
• PSA: 64.78000
• Density: 1.68±0.1 g/cm3(Predicted)
• LogP: 2.30600

Purity/Quality:

98% ^*data from raw suppliers

Pamiparib >98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Description: Pamiparib (BGB-290) is an investigational small molecule inhibitor of PARP1 and PARP2. Pamiparib is being evaluated as a monotherapy in pivotal clinical trials in China in recurrent platinum-sensitive and BRCA1/2 mutated ovarian cancers.

Technology Process of (R)-2-fluoro-10a-methyl-7,8,9,10,10a,11-hexahydro-5,6,7a,11-tetraazacyclohepta[def]cyclopenta[a]fluoren-4(5H)-one

There total 17 articles about (R)-2-fluoro-10a-methyl-7,8,9,10,10a,11-hexahydro-5,6,7a,11-tetraazacyclohepta[def]cyclopenta[a]fluoren-4(5H)-one 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: 94.0%

(R)-methyl 9-fluoro-11b-methyl-6-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole-7-carboxylate (1446261-61-5) → (10aR)-2-fluoro-5,8,9,10,10a,11-hexahydro-10a-methyl-5,6,7a,11-tetraazacyclohepta[def]cyclopenta[a]fluoren-4(7H)-one (1446261-44-4)

Guidance literature:

With hydrazine hydrate; acetic acid; In methanol; for 5h; Reflux;

DOI:10.1021/acs.jmedchem.0c01346

Reference yield:

methyl 3-amino-2-bromo-5-fluorobenzoate (1342063-52-8) → (10aR)-2-fluoro-5,8,9,10,10a,11-hexahydro-10a-methyl-5,6,7a,11-tetraazacyclohepta[def]cyclopenta[a]fluoren-4(7H)-one (1446261-44-4)

Guidance literature:

Multi-step reaction with 7 steps

1: potassium carbonate / dichloromethane / 5 - 25 °C / Inert atmosphere

2: copper(l) iodide; 1,1,3,3-tetramethylguanidine; bis-triphenylphosphine-palladium(II) chloride / N,N-dimethyl-formamide / 16 h / 80 °C / Inert atmosphere

3: zinc dibromide / toluene

4: sodium tetrahydroborate; methanol / 4 h / Reflux; Inert atmosphere

5: N-ethyl-N,N-diisopropylamine / acetonitrile / 20 h / 20 °C

6: 1 h / 60 °C / Reflux

7: hydrazine; acetic acid / methanol / 5 h / Reflux

With methanol; bis-triphenylphosphine-palladium(II) chloride; sodium tetrahydroborate; copper(l) iodide; 1,1,3,3-tetramethylguanidine; potassium carbonate; acetic acid; N-ethyl-N,N-diisopropylamine; zinc dibromide; hydrazine; In methanol; dichloromethane; N,N-dimethyl-formamide; toluene; acetonitrile;

Reference yield:

methyl 2-bromo-5-fluoro-3-(2,2,2-trifluoroacetamido)-benzoate (1446261-56-8) → (10aR)-2-fluoro-5,8,9,10,10a,11-hexahydro-10a-methyl-5,6,7a,11-tetraazacyclohepta[def]cyclopenta[a]fluoren-4(7H)-one (1446261-44-4)

Guidance literature:

Multi-step reaction with 6 steps

1: copper(l) iodide; 1,1,3,3-tetramethylguanidine; bis-triphenylphosphine-palladium(II) chloride / N,N-dimethyl-formamide / 16 h / 80 °C / Inert atmosphere

2: zinc dibromide / toluene

3: sodium tetrahydroborate; methanol / 4 h / Reflux; Inert atmosphere

4: N-ethyl-N,N-diisopropylamine / acetonitrile / 20 h / 20 °C

5: 1 h / 60 °C / Reflux

6: hydrazine; acetic acid / methanol / 5 h / Reflux

With methanol; bis-triphenylphosphine-palladium(II) chloride; sodium tetrahydroborate; copper(l) iodide; 1,1,3,3-tetramethylguanidine; acetic acid; N-ethyl-N,N-diisopropylamine; zinc dibromide; hydrazine; In methanol; N,N-dimethyl-formamide; toluene; acetonitrile;

upstream raw materials:

methyl 3-amino-2-bromo-5-fluorobenzoate

methyl 2-bromo-5-fluoro-3-(2,2,2-trifluoroacetamido)-benzoate

(R)-benzyl 2-((4-fluoro-2-(methoxycarbonyl)-6-(2,2,2-trifluoroacetamido)phenyl)ethynyl)-2-methylpyrrolidine-1-carboxylate

(R)-methyl 9-fluoro-11b-methyl-6-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole-7-carboxylate

Refernces

• 1、 -. "TREATMENT CANCERS USING A COMBINATION COMPRISING PARP INHIBITORS, TEMOZOLOMIDE AND/OR RADIATION THERAPY". Paragraph 0114; 0115. . Retrieved 2019/02/06.
• 2、 -. "TREATMENT CANCERS USING COMBINATION COMPRISING PARP INHIBITORS". Paragraph 0129-0130. . Retrieved 2018/06/16.