tert-butyl (1s,4s)-4-(2-(2'-((1,4-oxazepan-4-yl)methyl)-4'-hydroxybiphenyl-3-yloxy)-5-fluoronicotinamido)cyclohexylcarbamate

Base Information

• Chemical Name: tert-butyl (1s,4s)-4-(2-(2'-((1,4-oxazepan-4-yl)methyl)-4'-hydroxybiphenyl-3-yloxy)-5-fluoronicotinamido)cyclohexylcarbamate
• CAS No.: 1197291-06-7
• Molecular Formula: C₃₅H₄₃FN₄O₆
• Molecular Weight: 634.748
• Mol file: 1197291-06-7.mol

Synonyms:tert-butyl (1s,4s)-4-(2-(2'-((1,4-oxazepan-4-yl)methyl)-4'-hydroxybiphenyl-3-yloxy)-5-fluoronicotinamido)cyclohexylcarbamate

Chemical Property of tert-butyl (1s,4s)-4-(2-(2'-((1,4-oxazepan-4-yl)methyl)-4'-hydroxybiphenyl-3-yloxy)-5-fluoronicotinamido)cyclohexylcarbamate

Chemical Property:

Purity/Quality:

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

Technology Process of tert-butyl (1s,4s)-4-(2-(2'-((1,4-oxazepan-4-yl)methyl)-4'-hydroxybiphenyl-3-yloxy)-5-fluoronicotinamido)cyclohexylcarbamate

There total 6 articles about tert-butyl (1s,4s)-4-(2-(2'-((1,4-oxazepan-4-yl)methyl)-4'-hydroxybiphenyl-3-yloxy)-5-fluoronicotinamido)cyclohexylcarbamate 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: 62.0%

tert-butyl (1s,4s)-4-(5-fluoro-2-(2'-formyl-4'-hydroxybiphenyl-3-yloxy)nicotinamido)cyclohexylcarbamate (1197291-03-4) + homomorpholine hydrochloride (178312-62-4) → tert-butyl (1s,4s)-4-(2-(2'-((1,4-oxazepan-4-yl)methyl)-4'-hydroxybiphenyl-3-yloxy)-5-fluoronicotinamido)cyclohexylcarbamate (1197291-06-7)

Guidance literature:

tert-butyl (1s,4s)-4-(5-fluoro-2-(2'-formyl-4'-hydroxybiphenyl-3-yloxy)nicotinamido)cyclohexylcarbamate; homomorpholine hydrochloride; With acetic acid; sodium sulfate; In dichloromethane; at 18 - 25 ℃; for 1h; Inert atmosphere;

With sodium tris(acetoxy)borohydride; In dichloromethane; for 1.5h; Inert atmosphere;

DOI:10.1021/jm5001216

Reference yield:

tert-butyl N-[(1s,4s)-4-[5-fluoro-2-(3-iodophenoxy)nicotinamido]cyclohexyl]carbamate (1196806-69-5) → tert-butyl (1s,4s)-4-(2-(2'-((1,4-oxazepan-4-yl)methyl)-4'-hydroxybiphenyl-3-yloxy)-5-fluoronicotinamido)cyclohexylcarbamate (1197291-06-7)

Guidance literature:

Multi-step reaction with 3 steps

1.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; 1,1'-bis-(diphenylphosphino)ferrocene; potassium acetate / dimethyl sulfoxide / 16 h / 80 °C / Inert atmosphere

2.1: dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; potassium carbonate / acetonitrile; water / 3 h / 80 °C / Inert atmosphere

3.1: acetic acid; sodium sulfate / dichloromethane / 1 h / 18 - 25 °C / Inert atmosphere

3.2: 1.5 h / Inert atmosphere

With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; 1,1'-bis-(diphenylphosphino)ferrocene; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate; palladium diacetate; potassium carbonate; acetic acid; sodium sulfate; In dichloromethane; water; dimethyl sulfoxide; acetonitrile;

DOI:10.1021/jm5001216

Reference yield:

2-chloro-5-fluoronicotinic acid (38186-88-8) → tert-butyl (1s,4s)-4-(2-(2'-((1,4-oxazepan-4-yl)methyl)-4'-hydroxybiphenyl-3-yloxy)-5-fluoronicotinamido)cyclohexylcarbamate (1197291-06-7)

Guidance literature:

Multi-step reaction with 5 steps

1.1: triethylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / acetonitrile; tetrahydrofuran / 0 - 25 °C / Inert atmosphere

2.1: caesium carbonate / N,N-dimethyl-formamide / 48 h / 60 °C / Inert atmosphere

3.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; 1,1'-bis-(diphenylphosphino)ferrocene; potassium acetate / dimethyl sulfoxide / 16 h / 80 °C / Inert atmosphere

4.1: dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; potassium carbonate / acetonitrile; water / 3 h / 80 °C / Inert atmosphere

5.1: acetic acid; sodium sulfate / dichloromethane / 1 h / 18 - 25 °C / Inert atmosphere

5.2: 1.5 h / Inert atmosphere

With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; 1,1'-bis-(diphenylphosphino)ferrocene; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate; palladium diacetate; potassium carbonate; caesium carbonate; acetic acid; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; sodium sulfate; triethylamine; In tetrahydrofuran; dichloromethane; water; dimethyl sulfoxide; N,N-dimethyl-formamide; acetonitrile;

DOI:10.1021/jm5001216

upstream raw materials:

tert-butyl (1s,4s)-4-(5-fluoro-2-(2'-formyl-4'-hydroxybiphenyl-3-yloxy)nicotinamido)cyclohexylcarbamate

homomorpholine hydrochloride

tert-butyl N-[(1s,4s)-4-[5-fluoro-2-(3-iodophenoxy)nicotinamido]cyclohexyl]carbamate

2-chloro-5-fluoronicotinic acid

Downstream raw materials:

N-((1s,4s)-4-(5-fluoro-2-(4'-hydroxy-2'-(morpholinomethyl)biphenyl-3-yloxy)nicotinamido)cyclohexyl)-5-methylimidazo[1,2-a]pyridine-2-carboxamide trifluoroacetic acid salt

2-(2'-((1,4-oxazepan-4-yl)methyl)-4'-hydroxybiphenyl-3-yloxy)-N-((1s,4s)-4-aminocyclohexyl)-5-fluoronicotinamide

N-((1s,4s)-4-(2-(2'-((1,4-oxazepan-4-yl)methyl)-4'-hydroxybiphenyl-3-yloxy)-5-fluoronicotinamido)cyclohexyl)-5-methylimidazo[1,2-a]pyridine-2-carboxamide trifluoroacetic acid salt

N-((1s,4s)-4-(2-(2'-((1,4-oxazepan-4-yl)methyl)-4'-hydroxybiphenyl-3-yloxy)-5-fluoronicotinamido)cyclohexyl)-6-fluoroimidazo[1,2-a]pyridine-2-carboxamide trifluoroacetic acid salt

Refernces