106927-97-3

Basic information

• Product Name: (1S,9R)-tert-butyl 9-(1,3-dioxoisoindolin-2-yl)-10-oxooctahydro-1H-pyridazino[1,2-a][1,2]diazepine-1
• Synonyms: (1S,9R)-tert-butyl 9-(1,3-dioxoisoindolin-2-yl)-10-oxooctahydro-1H-pyridazino[1,2-a][1,2]diazepine-1;(1S,9R)-tert-butyl 9-(1,3-dioxoisoindolin-2-yl)-10-oxooctahydro-1H-pyridazino[1,2-a][1,2]diazepine-1-carboxylate;(1S,9S)-tert-butyl 9-(1,3-dioxoisoindolin-2-yl)-10-oxooctahydro-1H-pyridazino[1,2-a][1,2]diazepine-1-carboxylate;(1S,9S)-9-(1,3-Dihydro-1,3-dioxo-2H-isoindol-2-yl)octahydro-10-oxo-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid tert-butyl ester;(1S,9R)-tert-butyl 9-(1,3-dioxoisoindolin-2-yl)-10-oxooctahydro-1H-pyridazino[1,2-a][1,2];(1S,9R)-tert-Butyl 9-(1,3-dioxoisoindolin-2-yl)-10-oxooctahydro-1H-pyridazino[1,2-a][1,2]diazepin;(1S,9S)-tert-butyl 9-(1,3-dioxoisoindolin-2-yl)-10-oxooctahydro-1H-pyridazino[1,2-a][1,2]diazepine-1;(1S,9R)-tert-Butyl 9-(1,3-dioxoisoindolin-2-yl)-10-oxooctahydro-1H-pyridazino[1,2-a][1,2]diaze
• CAS NO: 106927-97-3
• Molecular Formula: C₂₂H₂₇N₃O₅
• Molecular Weight: 413.46688
• Mol File: 106927-97-3.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 538.028 °C at 760 mmHg
• Flash Point: 279.189 °C
• Appearance: /
• Density: 1.33
• Storage Temp.: 2-8°C
• PKA: 2.15±0.60(Predicted)
• CAS DataBase Reference: (1S,9R)-tert-butyl 9-(1,3-dioxoisoindolin-2-yl)-10-oxooctahydro-1H-pyridazino[1,2-a][1,2]diazepine-1(CAS DataBase Reference)
• NIST Chemistry Reference: (1S,9R)-tert-butyl 9-(1,3-dioxoisoindolin-2-yl)-10-oxooctahydro-1H-pyridazino[1,2-a][1,2]diazepine-1(106927-97-3)
• EPA Substance Registry System: (1S,9R)-tert-butyl 9-(1,3-dioxoisoindolin-2-yl)-10-oxooctahydro-1H-pyridazino[1,2-a][1,2]diazepine-1(106927-97-3)

Safety Data

• Hazardous Substances Data: 106927-97-3(Hazardous Substances Data)

Usage

General Description

The chemical "(1S,9R)-tert-butyl 9-(1,3-dioxoisoindolin-2-yl)-10-oxooctahydro-1H-pyridazino[1,2-a][1,2]diazepine-1" is a complex organic compound with a molecular structure containing a tert-butyl group, an isoindolin-2-yl group, and a pyridazino[1,2-a][1,2]diazepine-1 group. It is a bicyclic heterocycle with multiple functional groups, including ketones and a tert-butyl group. This chemical may have potential applications in medicinal chemistry, particularly in the development of novel pharmaceutical compounds targeting specific biological pathways or diseases. Its complex structure and potential pharmacological activities make it an interesting molecule for further research and development.

Synthetic route

(1S,9S)-t-butyl 1,2,3,4,7,8,9,10-octahydro-6,10-dioxo-9-phthalimidopyridazino<1,2-a><1,2>diazepine-1-carboxylate (106928-72-7) → (1S,9S)-t-butyl octahydro-10-oxo-9-phthalimido-6H-pyridazino<1,2-a><1,2>diazepine-1-carboxylate (106927-97-3)

Conditions	Yield
With borane-THF In tetrahydrofuran for 3h; Ambient temperature;	90%
With borane-THF In tetrahydrofuran at 0 - 5℃; for 3h; Inert atmosphere;

(S)-4-Chlorocarbonyl-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butyric acid benzyl ester (88767-16-2) → (1S,9S)-t-butyl octahydro-10-oxo-9-phthalimido-6H-pyridazino<1,2-a><1,2>diazepine-1-carboxylate (106927-97-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: NaHCO3 / toluene; H2O / 17 h / Ambient temperature 2: H2 / 5percent Pd-C / dimethylformamide / 18 h 3: SOCl2 / CH2Cl2 / 4 h / Ambient temperature 4: 90 percent / 1M borane in THF / tetrahydrofuran / 3 h / Ambient temperature View Scheme

(S,S)-5-(6-(tert-butoxycarbonyl)tetrahydropyridazin-1(2H)-yl)-4-(1,3-dioxoisoindolin-2-yl)-5-oxopentanoic acid (88767-18-4) → (1S,9S)-t-butyl octahydro-10-oxo-9-phthalimido-6H-pyridazino<1,2-a><1,2>diazepine-1-carboxylate (106927-97-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: SOCl2 / CH2Cl2 / 4 h / Ambient temperature 2: 90 percent / 1M borane in THF / tetrahydrofuran / 3 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: thionyl chloride / dichloromethane / 3 h / 10 - 15 °C / Inert atmosphere 2: borane-THF / tetrahydrofuran / 3 h / 0 - 5 °C / Inert atmosphere View Scheme

(S)-2-[(S)-4-Benzyloxycarbonyl-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butyryl]-tetrahydro-pyridazine-1,3-dicarboxylic acid 1-benzyl ester 3-tert-butyl ester (106860-13-3) → (1S,9S)-t-butyl octahydro-10-oxo-9-phthalimido-6H-pyridazino<1,2-a><1,2>diazepine-1-carboxylate (106927-97-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: H2 / 5percent Pd-C / dimethylformamide / 18 h 2: SOCl2 / CH2Cl2 / 4 h / Ambient temperature 3: 90 percent / 1M borane in THF / tetrahydrofuran / 3 h / Ambient temperature View Scheme

(3S)-N1-benzyloxycarbonyl-piperazic acid tert-butyl ester (72064-51-8) → (1S,9S)-t-butyl octahydro-10-oxo-9-phthalimido-6H-pyridazino<1,2-a><1,2>diazepine-1-carboxylate (106927-97-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: NaHCO3 / toluene; H2O / 17 h / Ambient temperature 2: H2 / 5percent Pd-C / dimethylformamide / 18 h 3: SOCl2 / CH2Cl2 / 4 h / Ambient temperature 4: 90 percent / 1M borane in THF / tetrahydrofuran / 3 h / Ambient temperature View Scheme

(2S)-4-benzyloxicarbonyl-2-phthalimidobutanoic acid (88784-33-2) → (1S,9S)-t-butyl octahydro-10-oxo-9-phthalimido-6H-pyridazino<1,2-a><1,2>diazepine-1-carboxylate (106927-97-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: SOCl2 / toluene 2: NaHCO3 / toluene; H2O / 17 h / Ambient temperature 3: H2 / 5percent Pd-C / dimethylformamide / 18 h 4: SOCl2 / CH2Cl2 / 4 h / Ambient temperature 5: 90 percent / 1M borane in THF / tetrahydrofuran / 3 h / Ambient temperature View Scheme

5-(2-((benzyloxy)carbonyl)-6-(tert-butoxycarbonyl)tetrahydropyridazin-1(2H)-yl)-4-(1,3-dioxoisoindolin-2-yl)-5-oxopentanoic acid → (1S,9S)-t-butyl octahydro-10-oxo-9-phthalimido-6H-pyridazino<1,2-a><1,2>diazepine-1-carboxylate (106927-97-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogen / palladium 10% on activated carbon / water; methanol / 3 h / 30 - 35 °C / 5149.01 - 5516.79 Torr / Autoclave 2: thionyl chloride / dichloromethane / 3 h / 10 - 15 °C / Inert atmosphere 3: borane-THF / tetrahydrofuran / 3 h / 0 - 5 °C / Inert atmosphere View Scheme

(1S,9S)-t-butyl octahydro-10-oxo-9-phthalimido-6H-pyridazino<1,2-a><1,2>diazepine-1-carboxylate (106927-97-3) → 9-amino-octahydro-10-oxo-6H-pyridazo[1,2-a][1,2]diazepine-1-(S)carboxylic acid t-butyl ester (106860-20-2)

Conditions	Yield
With hydrazine hydrate In ethanol for 1h; Ambient temperature;
With hydrazine hydrate In ethanol at 25 - 30℃; Inert atmosphere;

(1S,9S)-t-butyl octahydro-10-oxo-9-phthalimido-6H-pyridazino<1,2-a><1,2>diazepine-1-carboxylate (106927-97-3) → cilazapril (88768-40-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrazine hydrate / ethanol / 1 h / Ambient temperature 2: 10percent aq. Na2CO3 / CH2Cl2 / 5 h / Ambient temperature 3: 91 percent / HCl / CH2Cl2 / 16 h / Ambient temperature View Scheme
Multi-step reaction with 3 steps 1.1: hydrazine hydrate / ethanol / 25 - 30 °C / Inert atmosphere 2.1: 4-methyl-morpholine / toluene / 25 - 80 °C 3.1: hydrogenchloride / dichloromethane / 7 h / -5 - 0 °C 3.2: pH 4.4 - 4.5 View Scheme

(1S,9S)-t-butyl octahydro-10-oxo-9-phthalimido-6H-pyridazino<1,2-a><1,2>diazepine-1-carboxylate (106927-97-3) → (1S,9S)-t-butyl 9-<(1S)-ethoxycarbonyl-3-phenylpropylamino>octahydro-10-oxo-6H-pyridazino<1,2-a><1,2>diazepine-1-carboxylate (106860-19-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrazine hydrate / ethanol / 1 h / Ambient temperature 2: 10percent aq. Na2CO3 / CH2Cl2 / 5 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: hydrazine hydrate / ethanol / 25 - 30 °C / Inert atmosphere 2: 4-methyl-morpholine / toluene / 25 - 80 °C View Scheme

Upstream product

• 88784-33-2 (2S)-4-benzyloxicarbonyl-2-phthalimidobutanoic acid 
• 72064-51-8 (3S)-N¹-benzyloxycarbonyl-piperazic acid tert-butyl ester 
• 106860-13-3 (S)-2-[(S)-4-Benzyloxycarbonyl-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butyryl]-tetrahydro-pyridazine-1,3-dicarboxylic acid 1-benzyl ester 3-tert-butyl ester 
• 88767-18-4 (S,S)-5-(6-(tert-butoxycarbonyl)tetrahydropyridazin-1(2H)-yl)-4-(1,3-dioxoisoindolin-2-yl)-5-oxopentanoic acid 
• 88767-16-2 (S)-4-Chlorocarbonyl-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butyric acid benzyl ester 
• 106928-72-7 (1S,9S)-t-butyl 1,2,3,4,7,8,9,10-octahydro-6,10-dioxo-9-phthalimidopyridazino<1,2-a><1,2>diazepine-1-carboxylate 

Downstream Products

• 106860-19-9 (1S,9S)-t-butyl 9-<(1S)-ethoxycarbonyl-3-phenylpropylamino>octahydro-10-oxo-6H-pyridazino<1,2-a><1,2>diazepine-1-carboxylate 
• 88768-40-5 cilazapril 
• 106860-20-2 9-amino-octahydro-10-oxo-6H-pyridazo[1,2-a][1,2]diazepine-1-(S)carboxylic acid t-butyl ester 

Relevant articles and documents

PROCESS FOR THE PREPARATION OF AN INTERMEDIATE OF CILAZAPRIL

The present invention relates to a process for the preparation of optically pure (S,S)-6-t-butoxycarbonyl-hexahydro-1-pyridazinylcarbonyl-1,3-dioxo-2-isoindolebutyric acid, an intermediate for the preparation of cilazapril.