(S)-Morpholin-3-ylmethyl (4-((1-(3-fluorobenzyl)-1H-indazol-5-yl)amino)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl)carbamate

Base Information

• Chemical Name: (S)-Morpholin-3-ylmethyl (4-((1-(3-fluorobenzyl)-1H-indazol-5-yl)amino)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl)carbamate
• CAS No.: 714971-09-2
• Molecular Formula: C27H27FN8O3
• Molecular Weight: 530.562
• UNII: 2252724U5N
• DSSTox Substance ID: DTXSID60221714
• Nikkaji Number: J3.049.529B
• Wikidata: Q27075357
• NCI Thesaurus Code: C48380
• Pharos Ligand ID: XXHZ4FWHHR8Y
• Metabolomics Workbench ID: 153329
• ChEMBL ID: CHEMBL1645462
• Mol file: 714971-09-2.mol

Synonyms:(4-((1-(3-fluorophenyl)methyl)-1H-indazol-5-ylamino)-5-methylpyrrolo(2,1-f)(1,2,4)triazin-6-yl)carbamic acid 3-morpholinylmethyl ester;BMS 599626;BMS-599626;BMS599626

Chemical Property of (S)-Morpholin-3-ylmethyl (4-((1-(3-fluorobenzyl)-1H-indazol-5-yl)amino)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl)carbamate

Chemical Property:

• PKA: 7.27±0.46(Predicted)
• PSA: 119.63000
• Density: 1.484 g/cm³
• LogP: 4.33010
• Solubility.: ≥28.35 mg/mL in DMSO
• XLogP3: 2.8
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 8
• Exact Mass: 530.21901492
• Heavy Atom Count: 39
• Complexity: 828

Purity/Quality:

98%,99%, ^*data from raw suppliers

BMS599626 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=C2C(=NC=NN2C=C1NC(=O)OCC3COCCN3)NC4=CC5=C(C=C4)N(N=C5)CC6=CC(=CC=C6)F
• Isomeric SMILES: CC1=C2C(=NC=NN2C=C1NC(=O)OC[C@@H]3COCCN3)NC4=CC5=C(C=C4)N(N=C5)CC6=CC(=CC=C6)F
• Recent ClinicalTrials: Pharmacokinetics (PK) Study of AC480 for Recurrent Glioma
• Uses: BMS-599626 is a highly selective pan-HERKinase inhibitor with IC50 of 20 and 30 nM for the inhibition of HER1and HER2, respectively. It is a highly selective and potent inhibitor of HER1 and HER2 kinases and inhibits tumor cell proliferation through modulation of receptor signaling. BMS-599626 inhibits HER1/HER2 receptor heterodimerization and provides an additional mechanism of inhibiting tumors in which receptor coexpression and heterodimerization play a major role in driving tumor growth.

Technology Process of (S)-Morpholin-3-ylmethyl (4-((1-(3-fluorobenzyl)-1H-indazol-5-yl)amino)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl)carbamate

There total 6 articles about (S)-Morpholin-3-ylmethyl (4-((1-(3-fluorobenzyl)-1H-indazol-5-yl)amino)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl)carbamate 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: 77.0%

(S)-tert-butyl 3-((4-(1-(3-fluorobenzyl)-1H-indazol-5-ylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-ylcarbamoyloxy)methyl)morpholine-4-carboxylate (714971-12-7) → [4-[[1-(3-fluorophenyl)methyl]-1H-indazol-5-ylamino]-5-methyl-pyrrolo[2,1-f][1,2,4]triazin-6-yl]carbamic acid (3S)-3-morpholinylmethyl ester (714971-09-2)

Guidance literature:

With hydrogenchloride; In methanol; at 70 ℃;

Reference yield:

(R)-(4-benzylmorpholin-3-yl)methanol hydrochloride (714971-27-4) → [4-[[1-(3-fluorophenyl)methyl]-1H-indazol-5-ylamino]-5-methyl-pyrrolo[2,1-f][1,2,4]triazin-6-yl]carbamic acid (3S)-3-morpholinylmethyl ester (714971-09-2)

Guidance literature:

Multi-step reaction with 3 steps

1: potassium phosphate; hydrogen / palladium hydroxide/carbon / ethyl acetate / 45 h / 775.74 Torr

2: diphenyl phosphoryl azide; triethylamine / toluene / 77 - 87 °C

3: hydrogenchloride / methanol / 70 °C

With hydrogenchloride; potassium phosphate; diphenyl phosphoryl azide; hydrogen; triethylamine; palladium hydroxide/carbon; In methanol; ethyl acetate; toluene; 2: Curtius Rearrangement;

Reference yield:

(3S)-5-oxo-4-(phenylmethyl)-3-morpholinecarboxylic acid (106973-37-9) → [4-[[1-(3-fluorophenyl)methyl]-1H-indazol-5-ylamino]-5-methyl-pyrrolo[2,1-f][1,2,4]triazin-6-yl]carbamic acid (3S)-3-morpholinylmethyl ester (714971-09-2)

Guidance literature:

Multi-step reaction with 4 steps

1: dimethylsulfide borane complex; triethylamine / tetrahydrofuran / 6.5 h / 10 °C / Heating / reflux

2: potassium phosphate; hydrogen / palladium hydroxide/carbon / ethyl acetate / 45 h / 775.74 Torr

3: diphenyl phosphoryl azide; triethylamine / toluene / 77 - 87 °C

4: hydrogenchloride / methanol / 70 °C

With hydrogenchloride; potassium phosphate; dimethylsulfide borane complex; diphenyl phosphoryl azide; hydrogen; triethylamine; palladium hydroxide/carbon; In tetrahydrofuran; methanol; ethyl acetate; toluene; 3: Curtius Rearrangement;

upstream raw materials:

(S)-tert-butyl 3-((4-(1-(3-fluorobenzyl)-1H-indazol-5-ylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-ylcarbamoyloxy)methyl)morpholine-4-carboxylate

(R)-3-(hydroxymethyl)morpholine-4-carboxylic acid tert-butyl ester

4-(1-(3-fluorobenzyl)-1H-indazol-5-ylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid

(R)-(4-benzylmorpholin-3-yl)methanol hydrochloride

Refernces