33100-15-1

Usage

Uses

2-Nitrophenethylamine can be used as CGRP receptor antagonists.

Synthetic route

2-nitro-benzeneacetonitrile (610-66-2) → 2-(2-aminoethyl)nitrobenzene (33100-15-1)

Conditions	Yield
Stage #1: 2-nitro-benzeneacetonitrile With dimethylsulfide borane complex In tetrahydrofuran at 0℃; for 8h; Heating / reflux; Stage #2: With methanol for 1h; Heating / reflux;	100%
With borane-THF at 0 - 20℃; Inert atmosphere;	82%
With dimethylsulfide borane complex In tetrahydrofuran at 0 - 70℃; for 8h; Inert atmosphere;	82%
With borane-THF

3-(2-nitrophenyl)propionic acid (2001-32-3) → 2-(2-aminoethyl)nitrobenzene (33100-15-1)

Conditions	Yield
With hydrogen azide; chloroform; sulfuric acid

N-(2-nitro-phenethyl)-acetamide (315663-43-5) → 2-(2-aminoethyl)nitrobenzene (33100-15-1)

Conditions	Yield
With hydrogen bromide

phenethylamine (64-04-0) → 2-(p-nitrophenyl)ethylamine (24954-67-4) + 2-(2-aminoethyl)nitrobenzene (33100-15-1)

Conditions	Yield
With sulfuric acid; nitric acid

(2-bromoethyl)-2-nitrobenzene (16793-89-8) → 2-(2-aminoethyl)nitrobenzene (33100-15-1)

Conditions	Yield
(i) aq. NaN3, DMSO, (ii) Ph3P, benzene, (iii) aq. HBr, AcOH; Multistep reaction;
Stage #1: (2-bromoethyl)-2-nitrobenzene With sodium azide In water; acetonitrile for 20h; Heating / reflux; Stage #2: With triphenylphosphine In toluene at 20℃; for 16h; Stage #3: With sodium hydroxide; hydrogen bromide; acetic acid more than 3 stages;

2-(2-nitrophenyl)acetamide (31142-60-6) → 2-(2-aminoethyl)nitrobenzene (33100-15-1)

Conditions	Yield
With borane In 1,4-dioxane
With borane

2-nitro-benzeneethanol (15121-84-3) → 2-(2-aminoethyl)nitrobenzene (33100-15-1)

Conditions	Yield
With dmap; trifluoromethylsulfonic anhydride; ammonia 1.) CH2Cl2, from -30 deg C to RT, 2.) THF, from -30 deg C to RT; Multistep reaction;
Multi-step reaction with 2 steps 1: aq. HBr 2: (i) aq. NaN3, DMSO, (ii) Ph3P, benzene, (iii) aq. HBr, AcOH View Scheme

phenethylamine (64-04-0) + HNO3+H2SO4 → 2-(p-nitrophenyl)ethylamine (24954-67-4) + 2-(2-aminoethyl)nitrobenzene (33100-15-1)

nitric acid (7697-37-2) + phenethylamine (64-04-0) → 2-(p-nitrophenyl)ethylamine (24954-67-4) + 2-(2-aminoethyl)nitrobenzene (33100-15-1) + 2-(3-nitrophenyl)ethylamine (83304-13-6)

Conditions	Yield
at -10℃;

2-nitro-hydrocinnamic acid bromoamide → 2-(2-aminoethyl)nitrobenzene (33100-15-1)

Conditions	Yield
With potassium hydroxide at 80 - 90℃;

3-(2-nitro-phenyl)-propionic acid bromoamide + KOH-solution → 2-(2-aminoethyl)nitrobenzene (33100-15-1)

Conditions	Yield
at 80 - 90℃;

methyl-N-(benzyl-methyl)-formamide (877-95-2) → 2-(2-aminoethyl)nitrobenzene (33100-15-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: nitric acid / 0 °C 2: hydrobromic acid View Scheme

phenethylamine (64-04-0) → 2-(2-aminoethyl)nitrobenzene (33100-15-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 210 - 220 °C / durch Erhitzen zuletzt auf 290grad 2: nitric acid / 0 °C 3: hydrobromic acid View Scheme

ethyl 2-nitrophenylacetate (31912-02-4) → 2-(2-aminoethyl)nitrobenzene (33100-15-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaBH4, AlCl3 2: aq. HBr 3: (i) aq. NaN3, DMSO, (ii) Ph3P, benzene, (iii) aq. HBr, AcOH View Scheme

2-nitrophenethyl azide (33100-26-4) → 2-(2-aminoethyl)nitrobenzene (33100-15-1)

Conditions	Yield
Stage #1: 2-nitrophenethyl azide With triphenylphosphine; calcium carbonate In benzene at 20℃; Stage #2: With hydrogen bromide In water; acetic acid at 100℃; for 1h;
Stage #1: 2-nitrophenethyl azide With triphenylphosphine; calcium carbonate In benzene at 20℃; Stage #2: With hydrogen bromide; acetic acid In water at 100℃; for 1h; Stage #3: With sodium hydroxide In water
Stage #1: 2-nitrophenethyl azide With triphenylphosphine; calcium carbonate In benzene at 20℃; Stage #2: With hydrogen bromide; acetic acid In water at 100℃; for 1h; Stage #3: With sodium hydroxide In water

2-nitrophenethylamine hydrochloride → 2-(2-aminoethyl)nitrobenzene (33100-15-1)

Conditions	Yield
With sodium hydroxide; water
With sodium hydroxide In tetrahydrofuran; water pH=8 - 9;

phenylacetonitrile (140-29-4) → 2-(2-aminoethyl)nitrobenzene (33100-15-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: nitric acid; acetic acid / 0 - 40 °C 2: dimethylsulfide borane complex / tetrahydrofuran / 8 h / 0 - 70 °C / Inert atmosphere View Scheme

2-(2-aminoethyl)nitrobenzene (33100-15-1) → β-(o-aminophenyl)ethylamine (48108-93-6)

Conditions	Yield
With hydrogen; palladium 10% on activated carbon In ethanol under 2068.65 Torr; for 18h;	99%
With palladium 10% on activated carbon; hydrogen In ethanol at 20℃; under 2280.15 Torr;	99%
With phosphorus; hydrogen iodide
With ethanol; nickel Hydrogenation;
With hydrogen; palladium 10% on activated carbon In methanol for 18.0833h;

di-tert-butyl dicarbonate (24424-99-5) + 2-(2-aminoethyl)nitrobenzene (33100-15-1) → [2-(2-nitrophenyl)ethyl]carbamic acid tert-butyl ester (180147-33-5)

Conditions	Yield
With sodium hydrogencarbonate In 1,4-dioxane; water at 0 - 20℃;	92%

2-(2-aminoethyl)nitrobenzene (33100-15-1) + propyl N-cyano-3-pyridinecarboximidate (143966-30-7) → C15H13N5O2

Conditions	Yield
In methanol Ambient temperature;	64%

2-(2-aminoethyl)nitrobenzene (33100-15-1) → 1,4-dihydrocinnoline (1500-42-1)

Conditions	Yield
With acetate buffer; acetic acid In methanol; water redox electrolysis;	45%

2-(2-aminoethyl)nitrobenzene (33100-15-1) → ortho-nitrobenzoic acid (552-16-9)

Conditions	Yield
bei der Oxydation;

2-(2-aminoethyl)nitrobenzene (33100-15-1) → 2-amino-N-methylbenzylamine (1904-69-4)

Conditions	Yield
With hydrogenchloride; tin
With phosphorus; hydrogen iodide

2-(2-aminoethyl)nitrobenzene (33100-15-1) + benzenesulfonyl chloride (98-09-9) → N-Benzolsulfonyl-2-(2-nitrophenyl)-ethylamin (33100-17-3)

Conditions	Yield
With pyridine

2-(2-aminoethyl)nitrobenzene (33100-15-1) + methylamine (74-89-5) → methyl-(2-nitro-phenethyl)-amine (33100-16-2)

Conditions	Yield
In acetonitrile

2-(2-aminoethyl)nitrobenzene (33100-15-1) + (R)-Pantolacton (599-04-2) → opt.-akt.-<2-Nitro-phenaethyl>-pantoyl-amin

2-(2-aminoethyl)nitrobenzene (33100-15-1) → N-(2-nitro-phenethyl)-acetamide (315663-43-5)

Conditions	Yield
With acetylation reagent

2-(2-aminoethyl)nitrobenzene (33100-15-1) + N-(thiazol-2-yl)-1H-imidazole-1-carbothioamide (149485-85-8) → 1-[2-(2-Nitro-phenyl)-ethyl]-3-thiazol-2-yl-thiourea

Conditions	Yield
In acetonitrile at 100℃; for 1h;

2-(2-aminoethyl)nitrobenzene (33100-15-1) + N-{5-[2-(2-methyl-isothioureido)-thiazol-4-yl]-furan-2-ylmethyl}-acetamide; hydriodide → 4-<5-(acetamidomethyl)furan-2-yl>-2-<<(2-nitrophenyl)ethyl>guanidino>thiazole (168970-67-0)

Conditions	Yield
In ethanol for 72h; Heating; Yield given;

2-(2-aminoethyl)nitrobenzene (33100-15-1) → 4-<5-(acetamidomethyl)furan-2-yl>-2-<<(2-aminophenyl)ethyl>guanidino>thiazole (168971-00-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: ethanol / 72 h / Heating 2: 73 percent / H2 / 10 percent Pd/C / methanol / 760 Torr / Ambient temperature View Scheme

2-(2-aminoethyl)nitrobenzene (33100-15-1) → 4-<5-(acetamidomethyl)furan-2-yl>-2-<<(2-acetamidophenyl)ethyl>guanidino>thiazole

Conditions	Yield
Multi-step reaction with 3 steps 1: ethanol / 72 h / Heating 2: 73 percent / H2 / 10 percent Pd/C / methanol / 760 Torr / Ambient temperature 3: 57 percent / Et3N / CH2Cl2; dimethylformamide / 1 h / Ambient temperature View Scheme

2-(2-aminoethyl)nitrobenzene (33100-15-1) → N-[2-(2-aminophenyl)ethyl]acetamide (857273-34-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetylation reagent 2: reduction View Scheme

2-(2-aminoethyl)nitrobenzene (33100-15-1) → o-ethoxycarbonylimino-N-acetylphenethylamine (72359-20-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetylation reagent 2: reduction View Scheme

2-(2-aminoethyl)nitrobenzene (33100-15-1) → 1-benzoylamino-2-(2-benzoylamino-ethyl)-benzene

Conditions	Yield
Multi-step reaction with 2 steps 1: Raney nickel; ethanol / Hydrogenation View Scheme

Upstream product

• 2001-32-3 3-(2-nitrophenyl)propionic acid 
• 315663-43-5 N-(2-nitro-phenethyl)-acetamide 
• 64-04-0 phenethylamine 
• 16793-89-8 (2-bromoethyl)-2-nitrobenzene 
• 15121-84-3 2-nitro-benzeneethanol 
• 140-29-4 phenylacetonitrile 
• 861337-74-8 2-nitrophenethylamine hydrochloride 
• 33100-26-4 2-nitrophenethyl azide 
• 610-66-2 2-nitro-benzeneacetonitrile 
• 31912-02-4 ethyl 2-nitrophenylacetate 
• 877-95-2 methyl-N-(benzyl-methyl)-formamide 
• 7697-37-2 nitric acid 
• 31142-60-6 2-(2-nitrophenyl)acetamide 

Downstream Products

• 33100-21-9 N-Methyl-N-2-(2-nitrophenyl)-ethyl-β-alanin 
• 33100-18-4 Ethyl-N-2-(2-nitrophenyl)-ethyl-sarcosinat 
• 33100-19-5 Ethyl-N-methyl-N-2-(2-nitrophenyl)-ethyl-β-alanat 
• 33140-76-0 N-Benzolsulfonyl-N-2-(2-nitrophenyl)-ethylglycin 
• 33100-20-8 N-2-(2-Nitrophenyl)aethylsarcosin 
• 180147-33-5 [2-(2-nitrophenyl)ethyl]carbamic acid tert-butyl ester 
• 5339-07-1 2-(ortho-nitrophenyl)-N-benzylethylamine 
• 783368-11-6 tert-butyl 4-{[2-(2-nitrophenyl)ethyl]amino}piperidine-1-carboxylate 
• 72359-20-7 o-ethoxycarbonylimino-N-acetylphenethylamine 
• 857273-34-8 N-[2-(2-aminophenyl)ethyl]acetamide 
• 168971-00-4 4-<5-(acetamidomethyl)furan-2-yl>-2-<<(2-aminophenyl)ethyl>guanidino>thiazole 
• 168970-67-0 4-<5-(acetamidomethyl)furan-2-yl>-2-<<(2-nitrophenyl)ethyl>guanidino>thiazole 
• 172505-78-1 1-[2-(2-Nitro-phenyl)-ethyl]-3-thiazol-2-yl-thiourea 
• 315663-43-5 N-(2-nitro-phenethyl)-acetamide 

Relevant academic research and scientific papers

Substituted conformationally restricted guanidine derivatives: Probing the α2-adrenoceptors’ binding pocket

In this paper we report the design, synthesis and pharmacological evaluation of new N-substituted 2-amino-1,4-dihydroquinazolines, 2-amino-1,4-dihydropyridopyrimidines and 2-amino-4,5-dihydro-1,3-benzodiazepines as α2-adrenoceptors ligands. Computational studies show that the proposed substitutions and guanidine-containing ring size will probe an extensive area of the active site. Preparation of these molecules involved novel routes than those previously utilised in our laboratory for the preparation of the acyclic aryl-guanidine counterparts. Compounds 8b and 18c showed the highest affinity and antagonistic activity, within their series, towards the α2-adrenoceptor in human brain tissue in?vitro experiments. Structure-activity relationships have been established for the design and biological evaluation of novel α2-adrenoceptor ligands.

Design and synthesis of benzoazepin-2-one analogs as allosteric binders targeting the PIF pocket of PDK1

A novel series of benzoazepin-2-ones were designed and synthesized targeting the PIF pocket of AGC protein kinases, among which a series of thioether-linked benzoazepin-2-ones were discovered to bind to the PIF pocket of 3-phosphoinositide-dependent kinase-1 (PDK1), and to displace the PIF peptide with an EC50 values in the lower micromolar range. The structure-activity relationships (SARs) of the linker region, tail region, and distal region were explored to further optimize these novel binders which target the PIF pocket of PDK1. When tested in an in vitro PDK1 enzymatic assay using a peptide substrate, the benzodiazepin-2-ones increased the activity of the enzyme in a concentration-dependent fashion, indicating these compounds act as PDK1 allosteric activators. These new compounds may be further developed as therapeutic agents for the treatment of diseases where the PDK1-mediated AGC protein kinases are dysregulated.

Effect of potential amine prodrugs of selective neuronal nitric oxide synthase inhibitors on blood-brain barrier penetration

Several prodrug approaches were taken to mask amino groups in two potent and selective neuronal nitric oxide synthase (nNOS) inhibitors containing either a primary or secondary amino group to lower the charge and improve blood-brain barrier (BBB) penetration. The primary amine was masked as an azide and the secondary amine as an amide or carbamate. The azide was not reduced to the amine under a variety of in vitro and ex vivo conditions. Despite the decrease in charge of the amino group as an amide and as carbamates, BBB penetration did not increase. It appears that the uses of azides as prodrugs for primary amines or amides and carbamates as prodrugs for secondary amines are not universally effective for CNS applications.

CGRP receptor antagonists

The present invention relates to CGRP receptor antagonists, pharmaceutical compositions thereof, and methods therewith for treating CGRP receptor-mediated diseases and conditions.

HETEROCYCLIC BENZODIAZEPINE CGRP RECEPTOR ANTAGONISTS

Compounds of formula I: (where variables R2, R7, D, W, X, Y and Z are as described herein) which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

CGRP RECEPTOR ANTAGONISTS

Compounds of Formula (I): and Formula (II): (where variables R2, R4, A, B, D, W, X, Y and Z are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

COMPOUNDS, COMPOSITIONS AND METHODS

Compounds useful for treating cellular proliferative diseases and disorders by modulating the activity of KSP are disclosed.

CGRP RECEPTOR ANTAGONISTS

Compounds of Formula (I), (where variables R1, A, B, W, X, Y and Z are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

BENZODIAZEPINE CGRP RECEPTOR ANTAGONISTS

The present invention is directed to compounds of Formula I: I (where variables R1, R2, R3, R6, R7, G, J, W, X and Y are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

OXAZOLIDINONE DERIVATES N-SUBSTITUTED BY A TRICYCLIC RING, FOR USE AS ANTIBACTERIAL AGENTS

Compounds of formula (I) and methods for their preparation are disclosed. Further disclosed are methods of making biologically active compounds of formula (I) as well as pharmaceutically acceptable compositions comprising compounds of formula (I). Compounds of formula (I) as disclosed herein can be used in a variety of applications including use as antibacterial P is a tricyclic ring system as defined in claiml.