198989-07-0

Usage

Uses

Used in Pharmaceutical and Agrochemical Synthesis:
2,5-DIAZA-BICYCLO[2.2.1]HEPTANE-2-CARBOXYLIC ACID TERT-BUTYL ESTER is used as a building block for the synthesis of various pharmaceuticals and agrochemicals, due to its unique heterocyclic structure and reactivity, which can be incorporated into complex molecules with potential therapeutic or pesticidal properties.
Used as a Ligand for Metal Catalysts:
In the field of catalysis, 2,5-DIAZA-BICYCLO[2.2.1]HEPTANE-2-CARBOXYLIC ACID TERT-BUTYL ESTER is used as a ligand for metal catalysts, enhancing the efficiency and selectivity of various chemical reactions. Its ability to chelate with metal ions allows for the fine-tuning of catalytic processes.
Used in Organic Synthesis as a Reagent:
2,5-DIAZA-BICYCLO[2.2.1]HEPTANE-2-CARBOXYLIC ACID TERT-BUTYL ESTER serves as a reagent in organic synthesis, where it can be used to prepare a variety of other chemicals and compounds. Its versatility in forming different types of chemical bonds makes it a valuable tool in the synthesis of complex organic molecules.
Used in Research for Potential Biological Activities:
In the scientific community, 2,5-DIAZA-BICYCLO[2.2.1]HEPTANE-2-CARBOXYLIC ACID TERT-BUTYL ESTER is also used in research to explore its potential biological activities. Studies are conducted to understand its interactions with biological systems, which may lead to the discovery of new applications in medicine or other biological fields.
Used in Chemical Industry:
2,5-DIAZA-BICYCLO[2.2.1]HEPTANE-2-CARBOXYLIC ACID TERT-BUTYL ESTER is utilized in the chemical industry for the preparation of various specialty chemicals, taking advantage of its unique chemical properties and reactivity in diverse reaction conditions.

Synthetic route

2,5-diazabicyclo[2.2.1]heptane dihydrobromide + di-tert-butyl dicarbonate (24424-99-5) → tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0)

Conditions	Yield
With triethylamine In methanol at -30 - 25℃;	200 mg

1'-(5-(4-acetamidopyridin-2-yl)pyrimidin-2-yl)spiro-[cyclopropane-1,3'-indoline]-6'-carboxylic acid + tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) → tert-butyl 5-(1'-(5-(4-acetamidopyridin-2-yl)pyrimidin-2-yl)spiro[cyclopropane-1,3-indolin]-6'-ylcarbonyl)-2,5-diazabicyclo-[2.2.1]heptane-2-carboxylate

Conditions	Yield
With 4-methyl-morpholine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In N,N-dimethyl-formamide at 23℃; for 16h;	96.5%

Ethyl 4-bromobenzoate (5798-75-4) + tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) → tert-butyl 5-(4-(ethoxycarbonyl)phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate

Conditions	Yield
With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 110℃; for 24h;	92%

trifluoroacetic anhydride (407-25-0) + tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) → tert-butyl-2-(trifluoroacetyl)-2,5-diazabicyclo[2.2.1]heptane-5-carboxylate

Conditions	Yield
With triethylamine at 0 - 20℃; for 2.5 - 3.5h;	87.2%

2-chloropyridine (109-09-1) + tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) → tert-butyl 5-(pyridin-2-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate

Conditions	Yield
With methanesulfonato(2-dicyclohexylphosphino-2’,6’-di-i-propoxy-1,1’-biphenyl)(2’-methylamino-1,1‘-biphenyl-2-yl)palladium(II); sodium t-butanolate In 1,4-dioxane at 100℃; for 12h; Sealed tube; Inert atmosphere;	87%

6-chloronicotinonitrile (33252-28-7) + tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) → tert-butyl 5-(5-cyanopyridin-2-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 1.5h;	85%

3-(5-bromo-2-pyrimidinyl)-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine (651340-91-9) + tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) → tert-butyl 5-{2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl}-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylate

Conditions	Yield
With potassium tert-butylate; tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 60℃;	84%

9-ethyl-6,6-dimethyl-8-iodo-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile + tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) → C31H34N4O3

Conditions	Yield
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); sodium hexamethyldisilazane In tetrahydrofuran; 1,4-dioxane at 60℃; Inert atmosphere;	59%

7-chlorothiazolo[5,4-d]pyrimidin-5-amine (1211527-74-0) + tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) → tert-butyl 5-(5-aminothiazolo[5,4-d]pyrimidin-7-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (1435954-40-7)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 55℃; for 3h;	55.5%
With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 55℃; for 3h;	55.5%

4-Fluoronitrobenzene (350-46-9) + tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) → 5-(4-nitrophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (877212-94-7)

Conditions	Yield
In acetonitrile at 100℃;	52%
Stage #1: 4-Fluoronitrobenzene With potassium carbonate In dimethyl sulfoxide at 20℃; for 0.5h; Stage #2: tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate In dimethyl sulfoxide at 70℃; for 5h;

[(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (1188374-41-5) + tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) → 5-{2-[(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetyl}-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (1232028-17-9)

Conditions	Yield
Stage #1: [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.0333333h; Stage #2: tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate In N,N-dimethyl-formamide at 20℃;	51%

3-bromo-6-chloro-imidazo[1,2-b]pyridazine (13526-66-4) + tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) → tert-butyl 5-(3-bromoimidazo[1,2-b]pyridazin-6-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (1400874-04-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 130℃; for 4h;	49%

4-{[(2S,4R)-2-methyl-1-propionyl-1,2,3,4-tetrahydroquinolin-4-yl]amino}benzoic acid + tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) → tert-butyl 5-(4-{[(2S,4R)-2-methyl-1-propionyl-1,2,3,4-tetrahydroquinolin-4-yl]amino}benzoyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 16h;	49%

tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) + 2,3-dimethylbenzoic acid (603-79-2) → 5-(2,3-dimethylbenzoyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 17h;	42%

2-Fluoro-4-(trifluoromethyl)benzaldehyde (89763-93-9) + tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) → t-butyl 5-(2-formyl-5-(trifluoromethyl)phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 80℃;	34%

para-diiodobenzene (624-38-4) + tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) → tert-butyl 5-(4-iodophenyl)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylate (1197294-09-9)

Conditions	Yield
With potassium phosphate; copper(l) iodide; 1,1'-bi-2-naphthol In N,N-dimethyl-formamide at 80 - 90℃;	33%

3-fluoro-2-methylbenzoic acid (699-90-1) + tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) → 5-(3-fluoro-2-methylbenzoyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 17h;	31.62%

2-(3-((7-(3-chloropropoxy)quinazolin-4-yl)amino)-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide (722544-46-9) + tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) → 5-(3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

Conditions	Yield
With potassium carbonate In N,N-dimethyl acetamide at 60℃;	29%

1-Bromo-2-chloroethane (107-04-0) + tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (198989-07-0) → 5-(2-chloroethyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃; for 17h;	24.71%

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 

Downstream Products

• 920531-56-2 5-[1-(2-chloro-phenyl)-ethyl]-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester 
• 1197294-09-9 tert-butyl 5-(4-iodophenyl)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylate 
• 1426669-28-4 6-{4-[5-(tert-butoxycarbonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 
• 1232028-17-9 5-{2-[(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetyl}-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester 
• 877212-94-7 5-(4-nitrophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester 
• 198989-05-8 2-tBoc-5-diphenylmethyl-2,5-diazabicyclo[2.2.1]heptane 
• 871338-80-6 5-(3-chlorophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester 

Relevant academic research and scientific papers

SUBSTITUTED HETEROCYCLIC COMPOUNDS AS TROPOMYOSIN RECEPTOR KINASE A (TRKA) INHIBITORS

The present application relates to a series of substituted pyrazolo[1,5-a]pyridine compounds, their use as tropomyosin receptor kinase (Trk) family protein kinase inhibitors, method of making and pharmaceutical compositions comprising such compounds.

(R,R) AND (S,S) 2,5-DIAZABICYCLO [2,2,1]HEPTANE DERIVATIVES

Compounds of the Formulae I or II STR1 wherein Z and R 1, are as described herein which compounds are muscarinic agonists useful in treating central cholinergic disfunction and pharmaceutical compositions containing the compounds.