(2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride

Base Information

• Chemical Name: (2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride
• CAS No.: 1448189-80-7
• Molecular Formula: C₂₂H₃₀N₄O₃S*ClH
• Molecular Weight: 467.032
• Hs Code.: 2934100090
• Mol file: 1448189-80-7.mol

Synonyms:(2S,4R)-1-[(2S)-2-amino-3,3-dimethylbutanoyl]-4-hydroxy-N-{[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide hydrochloride

Chemical Property of (2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride

Chemical Property:

• Storage Temp.: 2-8°C

Purity/Quality:

98%HPLC ^*data from raw suppliers

(2S,4R)-1-((S)-2-Amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamideHydrochloride ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Description: VHL ligand 1 is a building block in the synthesis of proteolysis-targeting chimera technologies (PROTACs). It is the von Hippel-Lindau (VHL) E3 ligase binding portion of some VHL-based PROTACs, including BET PROTAC MZ1 (Item No. 21622).
• Uses: (2S,4R)-1-((S)-2-Amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide Hydrochloride acts as a reagent in the synthesis of PROTAC compounds that mediated the degration of oncogenic c-ABL and BCR-ABL. (S,R,S)-AHPC (HCl salt) is a ligand used in the recruitment of the von Hippel-Lindau (VHL) protein for targeted protein degradation and PROTAC (proteolysis-targeting chimeras) technology. This (S,R,S) conformation is the active variant, and (S,S,S) is the inactive derivative (cat#901487) used as a negative control.

Technology Process of (2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride

There total 16 articles about (2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride 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: 99.87%

tert‐butyl N‐[(2S)‐1‐[(2S,4R)‐4‐hydroxy‐2‐({[4‐(4‐methyl‐1,3‐thiazol‐5‐yl)phenyl]methyl}carbamoyl)pyrrolidin‐1‐yl]‐3,3‐dimethyl‐1‐oxobutan‐2‐yl]carbamate (1448189-98-7) → (2S,4R)-1-[(2S)-2-amino-3,3-dimethylbutanoyl]-4-hydroxy-N-{[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide hydrochloride (1448189-80-7,2115897-23-7)

Guidance literature:

With hydrogenchloride; In 1,4-dioxane; at 20 ℃; for 3h;

Reference yield:

(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid (13726-69-7,946610-68-0) → (2S,4R)-1-[(2S)-2-amino-3,3-dimethylbutanoyl]-4-hydroxy-N-{[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide hydrochloride (1448189-80-7,2115897-23-7)

Guidance literature:

Multi-step reaction with 5 steps

1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 0.5 h / 20 °C / Cooling with ice

2: palladium diacetate; potassium acetate / 1-methyl-pyrrolidin-2-one / 18 h / 120 °C / Inert atmosphere

3: hydrogenchloride / methanol; dichloromethane; 1,4-dioxane / 2 h / 20 °C

4: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 0.5 h / 20 °C

5: hydrogenchloride / methanol; dichloromethane; 1,4-dioxane / 1 h / 20 °C

With hydrogenchloride; potassium acetate; palladium diacetate; N-ethyl-N,N-diisopropylamine; HATU; In 1,4-dioxane; 1-methyl-pyrrolidin-2-one; methanol; dichloromethane; N,N-dimethyl-formamide;

Reference yield:

4-Bromobenzylamine (3959-07-7) → (2S,4R)-1-[(2S)-2-amino-3,3-dimethylbutanoyl]-4-hydroxy-N-{[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide hydrochloride (1448189-80-7,2115897-23-7)

Guidance literature:

Multi-step reaction with 5 steps

1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 0.5 h / 20 °C / Cooling with ice

2: palladium diacetate; potassium acetate / 1-methyl-pyrrolidin-2-one / 18 h / 120 °C / Inert atmosphere

3: hydrogenchloride / methanol; dichloromethane; 1,4-dioxane / 2 h / 20 °C

4: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 0.5 h / 20 °C

5: hydrogenchloride / methanol; dichloromethane; 1,4-dioxane / 1 h / 20 °C

With hydrogenchloride; potassium acetate; palladium diacetate; N-ethyl-N,N-diisopropylamine; HATU; In 1,4-dioxane; 1-methyl-pyrrolidin-2-one; methanol; dichloromethane; N,N-dimethyl-formamide;

upstream raw materials:

(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid

4-Bromobenzylamine

tert-butyl (2S,4R)-2-[(4-bromophenyl)methylcarbamoyl]-4-hydroxypyrrolidine-1-carboxylate

tert‐butyl (2S,4R)‐4‐hydroxy‐2‐({[4‐(4‐methyl‐1,3‐thiazol‐5‐yl)phenyl]methyl}carbamoyl)pyrrolidine‐1‐carboxylate

Downstream raw materials:

(2S,4R)-1-((S)-2-(tert-butyl)-19-((7R,8R,9S,13S,14S,17S)-3-hydroxy-17-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-7-yl)-4-oxo-6,9,12,15-tetraoxa-3-azanonadecan-1-oyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide

(2S,4R)-1-((S)-2-(tert-butyl)-18-((7R,8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-7-yl)-4-oxo-6,9,12-trioxa-3-azaoctadecan-1-oyl)-4-hydroxy-N-( 4-( 4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide

(2S,4R)-1-((S)-2-(2-(2-(2-(4-(4-((7R,8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-7-yl)butyl)-2-oxopiperazin-1-yl)ethoxy)ethoxy)acetamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide

(2S,4R)-1-((S)-2-(2-(4-((7R,8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-7-yl)butoxy)acetamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide