77086-21-6

Basic information

• Product Name: Dizocilpine
• Synonyms: Dizocilpine;(5S)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5α,10α-imine;[5S,10R,(+)]-10,11-Dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine;[5S,10R,(+)]-10,11-Dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5α,10α-imine;C13737;MK-801 (Dizocilpine);5H-Dibenzo[a,d]cyclohepten-5,10-imine, 10,11-dihydro-5-methyl-, (5S,10R)-;Dizocilpine free base(MK801)
• CAS NO: 77086-21-6
• Molecular Formula: C₁₆H₁₅N
• Molecular Weight: 221.297
• Product Categories: Inhibitors
• Mol File: 77086-21-6.mol
• Article Data: 3

Chemical Properties

• Melting Point: 68.5-69°
• Boiling Point: 320.3°C at 760 mmHg
• Flash Point: 152.6°C
• Appearance: /
• Density: 1.144g/cm³
• Vapor Pressure: 0.000321mmHg at 25°C
• Refractive Index: 1.632
• PKA: 7.96±0.40(Predicted)
• CAS DataBase Reference: Dizocilpine(CAS DataBase Reference)
• NIST Chemistry Reference: Dizocilpine(77086-21-6)
• EPA Substance Registry System: Dizocilpine(77086-21-6)

Safety Data

• Hazardous Substances Data: 77086-21-6(Hazardous Substances Data)

Usage

Uses

Neuroprotective.

InChI:InChI=1/C16H15N/c1-16-13-8-4-2-6-11(13)10-15(17-16)12-7-3-5-9-14(12)16/h2-9,15,17H,10H2,1H3/t15-,16+/m1/s1

Synthetic route

(5S,10R)-(+)-5-(bromomethyl)-10,11-dihydro-5H-dibenzo-[a,d]-cyclohepten-5,10-imine (159170-13-5) → Dizocilpine (77086-21-6)

Conditions	Yield
With lithium triethylborohydride In tetrahydrofuran at 60℃; for 3h;	85%

(5S,10R)-(+)-5-(hydroxymethyl)-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine (380427-51-0) → Dizocilpine (77086-21-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: HCO2Et 1.2: 81 percent / SOBr2; aq. HBr 2.1: 85 percent / LiBHEt3 / tetrahydrofuran / 3 h / 60 °C View Scheme

1-(2-bromo-phenyl)-1-cyano-1H-isoquinoline-2-carboxylic acid vinyl ester → Dizocilpine (77086-21-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 85 percent / Bu3SnH; AIBN / benzene / 1.5 h / Heating 2.1: aq. NaOH / ethanol / Heating 2.2: 89 percent / LiAlH4 / tetrahydrofuran / 40 h 3.1: HCO2Et 3.2: 81 percent / SOBr2; aq. HBr 4.1: 85 percent / LiBHEt3 / tetrahydrofuran / 3 h / 60 °C View Scheme

(5S,10R)-(+)-N-carboxylic acid vinyl ester-5-cyano-10,11-dihydro-5H-dibenzo[a,d]-cyclopenten-5,10-imine (380427-50-9) → Dizocilpine (77086-21-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: aq. NaOH / ethanol / Heating 1.2: 89 percent / LiAlH4 / tetrahydrofuran / 40 h 2.1: HCO2Et 2.2: 81 percent / SOBr2; aq. HBr 3.1: 85 percent / LiBHEt3 / tetrahydrofuran / 3 h / 60 °C View Scheme

Dizocilpine (77086-21-6) → (+)-2-nitro-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine + (+)-3-nitro-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine

Conditions	Yield
With sulfuric acid; nitric acid; acetic acid for 104h; Ambient temperature;	A 3% B 80%

Dizocilpine (77086-21-6) + methyl iodide (74-88-4) → N,5-dimethyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine methiodide (1222094-08-7)

Conditions	Yield
In diethyl ether for 96h; Darkness;	60%

Dizocilpine (77086-21-6) → (+)-N-<(tert-butyloxy)carbonyl>-2-amino-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine

Conditions	Yield
Multi-step reaction with 3 steps 1: 3 percent / sulfuric acid, glacial acetic acid, fumic nitric acid / 104 h / Ambient temperature 2: 90 percent / aq. NaHCO3 / CHCl3 / 36 h / Ambient temperature 3: 57 percent / H2 / 10percent Pd/C / ethyl acetate / 16 h / 2327.2 Torr / Ambient temperature View Scheme

Dizocilpine (77086-21-6) → (+)-N-<(tert-butyloxy)carbonyl>-2-isothiocyanato-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine

Conditions	Yield
Multi-step reaction with 4 steps 1: 3 percent / sulfuric acid, glacial acetic acid, fumic nitric acid / 104 h / Ambient temperature 2: 90 percent / aq. NaHCO3 / CHCl3 / 36 h / Ambient temperature 3: 57 percent / H2 / 10percent Pd/C / ethyl acetate / 16 h / 2327.2 Torr / Ambient temperature 4: 95 percent / aq. NaHCO3 / CHCl3 / 0.17 h View Scheme

Dizocilpine (77086-21-6) → (+)-N-<(tert-butyloxy)carbonyl>-2-nitro-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine

Conditions	Yield
Multi-step reaction with 2 steps 1: 3 percent / sulfuric acid, glacial acetic acid, fumic nitric acid / 104 h / Ambient temperature 2: 90 percent / aq. NaHCO3 / CHCl3 / 36 h / Ambient temperature View Scheme

Dizocilpine (77086-21-6) → (+)-2-isothiocyanato-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine hydrochloride

Conditions

Yield

Multi-step reaction with 5 steps 1: 3 percent / sulfuric acid, glacial acetic acid, fumic nitric acid / 104 h / Ambient temperature 2: 90 percent / aq. NaHCO3 / CHCl3 / 36 h / Ambient temperature 3: 57 percent / H2 / 10percent Pd/C / ethyl acetate / 16 h / 2327.2 Torr / Ambient temperature 4: 95 percent / aq. NaHCO3 / CHCl3 / 0.17 h 5: 75 percent / HCl (gas) / diethyl ether / 1 h / 0 - 20 °C View Scheme

Dizocilpine (77086-21-6) → (+)-N-<(tert-butyloxy)carbonyl>-3-amino-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine

Conditions	Yield
Multi-step reaction with 3 steps 1: 80 percent / sulfuric acid, glacial acetic acid, fumic nitric acid / 104 h / Ambient temperature 2: 98 percent / aq. NaHCO3 / CH2Cl2 / 39 h / Ambient temperature 3: 91 percent / H2 / 10percent Pd/C / ethanol / 16 h / 1551.4 Torr / Ambient temperature View Scheme

Dizocilpine (77086-21-6) → (+)-N-<(tert-butyloxy)carbonyl>-3-isothiocyanato-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine

Conditions	Yield
Multi-step reaction with 4 steps 1: 80 percent / sulfuric acid, glacial acetic acid, fumic nitric acid / 104 h / Ambient temperature 2: 98 percent / aq. NaHCO3 / CH2Cl2 / 39 h / Ambient temperature 3: 91 percent / H2 / 10percent Pd/C / ethanol / 16 h / 1551.4 Torr / Ambient temperature 4: 90 percent / aq. NaHCO3 / CHCl3 / 0.17 h View Scheme

Dizocilpine (77086-21-6) → (+)-N-<(tert-butyloxy)carbonyl>-3-nitro-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / sulfuric acid, glacial acetic acid, fumic nitric acid / 104 h / Ambient temperature 2: 98 percent / aq. NaHCO3 / CH2Cl2 / 39 h / Ambient temperature View Scheme

Dizocilpine (77086-21-6) → (+)-3-isothiocyanato-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine hydrochloride

Conditions

Yield

Multi-step reaction with 5 steps 1: 80 percent / sulfuric acid, glacial acetic acid, fumic nitric acid / 104 h / Ambient temperature 2: 98 percent / aq. NaHCO3 / CH2Cl2 / 39 h / Ambient temperature 3: 91 percent / H2 / 10percent Pd/C / ethanol / 16 h / 1551.4 Torr / Ambient temperature 4: 90 percent / aq. NaHCO3 / CHCl3 / 0.17 h 5: 89 percent / HCl (gas) / diethyl ether / 1 h / 0 - 20 °C View Scheme

Dizocilpine (77086-21-6) → C16H(2)H14N

Conditions	Yield
Stage #1: Dizocilpine With aluminum oxide; 5% rhodium on alumina; deuterium at 170℃; under 250 Torr; for 0.333333h; Stage #2: With ethanol

Dizocilpine (77086-21-6) → C16H(3)H14N

Conditions	Yield
Stage #1: Dizocilpine With aluminum oxide; tritium; 5% rhodium on alumina at 170℃; under 250 Torr; for 0.333333h; Stage #2: With ethanol

formaldehyd (50-00-0) + Dizocilpine (77086-21-6) → N,5-dimethyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (125133-02-0)

Conditions	Yield
With sodium cyanoborohydride; acetic acid In ethanol; water for 3h; Inert atmosphere;	140 mg

Upstream product

• 159170-13-5 (5S,10R)-(+)-5-(bromomethyl)-10,11-dihydro-5H-dibenzo-[a,d]-cyclohepten-5,10-imine 
• 380427-51-0 (5S,10R)-(+)-5-(hydroxymethyl)-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine 
• 380427-50-9 (5S,10R)-(+)-N-carboxylic acid vinyl ester-5-cyano-10,11-dihydro-5H-dibenzo[a,d]-cyclopenten-5,10-imine 
• 124070-25-3 C₂₁H₂₄N₂ 
• 50537-17-2 (+/-)-des-methyl MK-801 
• 124070-07-1 C₂₀H₂₂N₂ 
• 1210-35-1 10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-one 
• 2732-90-3 5-methylene-10,11-dihydro-5H-dibenzo[a,d]cycloheptene 
• 24167-43-9 5-methyl-10,11-dihydro-5H-dibenzo[a,d][7]annulene 

Downstream Products

• 125134-28-3 (5S,10R)-(+)-3-bromo-10,11-dihydro-5-methyl-5H-dibenzocyclohepten-5,10-imine 

Relevant articles and documents

Intermolecular Radical C(sp3)?H Amination under Iodine Catalysis

The direct amination of aliphatic C?H bonds has remained one of the most tantalizing transformations in organic chemistry. Herein, we report on a unique catalyst system, which enables the elusive intermolecular C(sp3)?H amination. This practical synthetic strategy provides access to aminated building blocks and fosters innovative multiple C?H amination within a new approach to aminated heterocycles. The synthetic utility is demonstrated by the synthesis of four relevant pharmaceuticals.

A BRIDGEHEAD α-AMINO CARBANION: FACILE PREPARATION OF C5(BRIDGEHEAD)-SUBSTITUTED ANALOGUES OF (+/-)-5H-DIBENZOCYCLOHEPTEN-5,10-IMINE INCLUDING A STABLE α-IODO SECONDARY AMINE

The preparation of C5(bridgehead)-substituted analogues of (+/-)-5H-dibenzocyclohepten-5,10-imine via α-lithiation of a tert-butylformamidine precursor is presented.