1-({3-[5-({(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-phenylpropyl}oxy)-1H-indazol-1-yl]phenyl}carbonyl)-D-prolinamide

Base Information

• Chemical Name: 1-({3-[5-({(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-phenylpropyl}oxy)-1H-indazol-1-yl]phenyl}carbonyl)-D-prolinamide
• CAS No.: 1196452-04-6
• Molecular Formula: C₃₁H₃₁F₂N₅O₄
• Molecular Weight: 575.615
• Mol file: 1196452-04-6.mol

Synonyms:1-({3-[5-({(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-phenylpropyl}oxy)-1H-indazol-1-yl]phenyl}carbonyl)-D-prolinamide

Chemical Property of 1-({3-[5-({(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-phenylpropyl}oxy)-1H-indazol-1-yl]phenyl}carbonyl)-D-prolinamide

Chemical Property:

Purity/Quality:

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

Technology Process of 1-({3-[5-({(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-phenylpropyl}oxy)-1H-indazol-1-yl]phenyl}carbonyl)-D-prolinamide

There total 10 articles about 1-({3-[5-({(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-phenylpropyl}oxy)-1H-indazol-1-yl]phenyl}carbonyl)-D-prolinamide 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: 29.0%

2,2-difluoropropanoic acid (373-96-6) + (R)-1-(3-(5-((1R,2S)-2-amino-1-phenylpropoxy)-1H-indazol-1-yl)benzoyl)pyrrolidine-2-carboxamide (1196452-40-0) → 1-({3-[5-({(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-phenylpropyl}oxy)-1H-indazol-1-yl]phenyl}carbonyl)-D-prolinamide (1196452-04-6)

Guidance literature:

2,2-difluoropropanoic acid; With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 16 - 25 ℃;

(R)-1-(3-(5-((1R,2S)-2-amino-1-phenylpropoxy)-1H-indazol-1-yl)benzoyl)pyrrolidine-2-carboxamide; In tetrahydrofuran; N,N-dimethyl-formamide;

Reference yield:

3-(2-(2-fluoro-5-iodobenzylidene)hydrazinyl)benzoic acid → 1-({3-[5-({(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-phenylpropyl}oxy)-1H-indazol-1-yl]phenyl}carbonyl)-D-prolinamide (1196452-04-6)

Guidance literature:

Multi-step reaction with 6 steps

1.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 0.5 h / 160 °C

2.1: sodium carbonate / 1-methyl-pyrrolidin-2-one / 40 - 55 °C

3.1: dimethylaminoacetic acid; caesium carbonate; copper(l) iodide / 0.5 h / 110 °C

3.2: 19 h / 110 °C / Sealed tube

4.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / dichloromethane / 2.5 h / 20 °C

5.1: lithium hydroxide / methanol; water; tetrahydrofuran / 3 h

6.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide

With copper(l) iodide; dimethylaminoacetic acid; potassium tert-butylate; sodium carbonate; caesium carbonate; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; lithium hydroxide; In tetrahydrofuran; 1-methyl-pyrrolidin-2-one; methanol; dichloromethane; water; N,N-dimethyl-formamide; 3.1: |Ullmann Condensation / 3.2: |Ullmann Condensation;

DOI:10.1021/acs.jmedchem.7b01215

Reference yield:

bromobenzene (108-86-1,52753-63-6) → 1-({3-[5-({(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-phenylpropyl}oxy)-1H-indazol-1-yl]phenyl}carbonyl)-D-prolinamide (1196452-04-6)

Guidance literature:

Multi-step reaction with 7 steps

1.1: TurboGrignard / tetrahydrofuran / 0 - 10 °C

1.2: 0 - 20 °C

2.1: aluminum isopropoxide; isopropyl alcohol / toluene / 50 °C

3.1: hydrogenchloride

4.1: dimethylaminoacetic acid; caesium carbonate; copper(l) iodide / 0.5 h / 110 °C

4.2: 19 h / 110 °C / Sealed tube

5.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / dichloromethane / 2.5 h / 20 °C

6.1: lithium hydroxide / methanol; water; tetrahydrofuran / 3 h

7.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide

With hydrogenchloride; copper(l) iodide; TurboGrignard; dimethylaminoacetic acid; aluminum isopropoxide; caesium carbonate; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; isopropyl alcohol; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; lithium hydroxide; In tetrahydrofuran; methanol; dichloromethane; water; N,N-dimethyl-formamide; toluene; 2.1: |Meerwein-Ponndorf-Verley Reduction / 4.1: |Ullmann Condensation / 4.2: |Ullmann Condensation;

DOI:10.1021/acs.jmedchem.7b01215

upstream raw materials:

2,2-difluoropropanoic acid

(R)-1-(3-(5-((1R,2S)-2-amino-1-phenylpropoxy)-1H-indazol-1-yl)benzoyl)pyrrolidine-2-carboxamide

bromobenzene

tert-butyl ((1R,2S)-1-hydroxy-1-phenylpropan-2-yl)carbamate

Refernces

• 1、 -. "PHENYL OR PYRIDINYL SUBSTITUTED INDAZOLES DERIVATIVES". Page/Page column 31. . Retrieved 2009/12/27.