946598-34-1 (反式-2-[4-(Boc-氨基)环己基]乙酸乙酯,ethyl 2-(1r,4r)-4-{(tert-butoxy)carbonylamino}cyclohexylacetate)

反应条件：

1.1 Reagents: Potassium carbonate Solvents: Acetonitrile ; overnight, 50 °C

参考文献：

Subtle Modifications to the Indole-2-carboxamide Motif of the Negative Allosteric Modulator N-((trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652) Yield Dramatic Changes in Pharmacological Activity at the Dopamine D2 Receptor

Kopinathan, Anitha; Draper-Joyce, Christopher; Szabo, Monika; Christopoulos, Arthur; Scammells, Peter J. ; et al, Journal of Medicinal Chemistry, 2019, 62(1), 371-377

合成路线：1 步

189153-10-4

75-03-6

_100%

反应条件：

1.1 Reagents: Potassium carbonate Solvents: Acetonitrile ; 1.75 h, rt; 3 h, reflux; overnight, 50 °C; 2 h, reflux

参考文献：

Discovery of a Novel Class of Negative Allosteric Modulator of the Dopamine D2 Receptor Through Fragmentation of a Bitopic Ligand

Mistry, Shailesh N.; Shonberg, Jeremy; Draper-Joyce, Christopher J.; Klein Herenbrink, Carmen; Michino, Mayako; et al, Journal of Medicinal Chemistry, 2015, 58(17), 6819-6843

合成路线：1 步

_96%

反应条件：

1.1 Reagents: Triethylamine Solvents: Dichloromethane ; 2 h, rt

参考文献：

Structure-activity study of N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652), a bitopic ligand that acts as a negative allosteric modulator of the dopamine D2 receptor

Shonberg, Jeremy; Draper-Joyce, Christopher; Mistry, Shailesh N.; Christopoulos, Arthur; Scammells, Peter J.; et al, Journal of Medicinal Chemistry, 2015, 58(13), 5287-5307

合成路线：1 步

_95%

反应条件：

1.1 Reagents: Triethylamine Solvents: Dichloromethane ; 5 - 10 °C; 10 °C → 30 °C; 2 h, 20 - 30 °C
1.2 Reagents: Sodium carbonate ; 20 - 30 °C; 15 min, 20 - 30 °C

参考文献：

Preparation of caliprazine and its intermediate

, China, , ,

合成路线：1 步

_95%

反应条件：

1.1 Reagents: Sodium bicarbonate , Tetrabutylammonium bromide Solvents: Tetrahydrofuran , Water ; 45 min, rt; 60 min, rt

参考文献：

A process for preparation of cariprazine and intermediates thereof

, India, , ,

合成路线：1 步

2093293-75-3

_94%

反应条件：

1.1 Reagents: Hydrogen Catalysts: Palladium Solvents: Ethanol ; 10 h, 0.6 MPa, rt

参考文献：

Process for the preparation of cariprazine

, China, , ,

合成路线：1 步

_94%

反应条件：

1.1 Reagents: Triethylamine Solvents: Dichloromethane ; 2 - 24 h, rt

参考文献：

A Structure-Activity Analysis of Biased Agonism at the Dopamine D2 Receptor

Shonberg, Jeremy; Herenbrink, Carmen Klein; Lopez, Laura; Christopoulos, Arthur; Scammells, Peter J.; et al, Journal of Medicinal Chemistry, 2013, 56(22), 9199-9221

合成路线：1 步

_93%

反应条件：

1.1 Reagents: Triethylamine Solvents: Dichloromethane ; rt → 10 °C
1.2 Solvents: Dichloromethane ; 1 h, 5 - 10 °C; 10 °C → rt; rt

参考文献：

Piperazine salt and a process for the preparation thereof

, World Intellectual Property Organization, , ,

合成路线：1 步

2730168-74-6

_92%

反应条件：

1.1 Reagents: Hydrochloric acid Catalysts: Iron Solvents: Methanol ; 0 °C; 5 h, 0 °C
1.2 Reagents: Sodium carbonate Solvents: Dichloromethane ; 1 h, rt
1.3 Reagents: Acetic anhydride ; 5 h, rt

参考文献：

Preparation method of inversion of configuration, a key intermediate of cariprazine

, China, , ,

合成路线：1 步

_90%

反应条件：

1.1 Reagents: Triethylamine Solvents: Dichloromethane ; 5 - 10 °C; 20 min, 5 - 10 °C; 10 h, 5 - 10 °C

参考文献：

Preparation of cariprazine and its intermediates

, China, , ,

合成路线：1 步

_87%

反应条件：

1.1 Reagents: Sodium bicarbonate Solvents: Water ; 15 min, rt
1.2 Catalysts: Tetrabutylammonium bromide Solvents: 1,2-Dimethoxyethane ; 15 min, rt
1.3 Solvents: Tetrahydrofuran , Water ; 45 min, rt; 60 min, rt; rt → 5 °C; 3 - 4 h, 2 - 5 °C

参考文献：

A process for preparation of Cariprazine and intermediates thereof

, India, , ,

合成路线：1 步

_60%

反应条件：

1.1 Reagents: Triethylamine Catalysts: 4-(Dimethylamino)pyridine Solvents: Dichloromethane ; 8 h, rt
1.2 Reagents: Water

参考文献：

Preparation of benzoisoxazolylpiperazinylethylcyclohexane derivatives for use as dopamine D3 and serotonin 5-HT2a receptor modulators

, World Intellectual Property Organization, , ,

合成路线：1 步

_60%

反应条件：

1.1 Reagents: Triethylamine Catalysts: 4-(Dimethylamino)pyridine Solvents: Dichloromethane ; 8 h, rt

参考文献：

Preparation of benzoyl-piperidine derivatives as dual modulators of the 5-HT2a and D3 receptors

, World Intellectual Property Organization, , ,

合成路线：1 步

_60%

反应条件：

1.1 Reagents: Triethylamine Catalysts: 4-(Dimethylamino)pyridine Solvents: Dichloromethane ; 8 h, rt

参考文献：

Preparation of benzo[d]isoxazole derivatives as dual modulators of 5-HT2A and D3 receptors

, World Intellectual Property Organization, , ,

合成路线：1 步

_60%

反应条件：

1.1 Reagents: Triethylamine Catalysts: 4-(Dimethylamino)pyridine Solvents: Dichloromethane ; 8 h, rt

参考文献：

Preparation of trans-1-[2-(4-aminocyclohexyl)ethyl]piperidin-4-ol ether derivatives as dual modulators of serotonin 5-HT2a receptor and dopamine D3 receptor

, United States, , ,

合成路线：1 步

_60%

反应条件：

1.1 Reagents: Triethylamine Catalysts: 4-(Dimethylamino)pyridine Solvents: Dichloromethane ; 8 h, rt
1.2 Reagents: Water ; rt

参考文献：

Benzoyl-piperidine derivatives as 5HT2/D3 modulators and their preparation, pharmaceutical compositions and use in the treatment of CNS disorders

, World Intellectual Property Organization, , ,

合成路线：1 步

参考文献：

Process for the preparation of cariprazine

, India, , ,

合成路线：1 步

2093293-75-3