Synthesis toward CRHR1 Antagonists through 2,7-Dimethylpyrazolo[1,5-α][1,3,5]triazin-4(3H)-one C-H Arylation

被引：7

作者：

Long, Jinghai ^{[1
]}

Lee, Woong-Sup ^{[1
]}

Chough, Chieyeon ^{[1
]}

Bae, Il Hak ^{[1
]}

Kim, B. Moon ^{[1
]}

机构：

[1] Seoul Natl Univ, Coll Nat Sci, Dept Chem, Seoul 151747, South Korea

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2015年 / 80卷 / 09期

基金：

新加坡国家研究基金会;

关键词：

CORTICOTROPIN-RELEASING-FACTOR; HORMONE TYPE-1 RECEPTOR; CATALYZED DIRECT ARYLATION; FACTOR CRF RECEPTOR; STRESS-INDUCED RELAPSE; BEHAVIORAL-RESPONSES; IMAGING AGENTS; RAT-BRAIN; NONPEPTIDE ANTAGONIST; PYRAZOLE DERIVATIVES;

D O I：

10.1021/jo502894r

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A novel synthetic protocol for 8-aryl substituted pyrazolo[1,5-alpha] [1,3,5]triazin-4(3H)-ones was developed employing Pd-catalyzed C-H arylation. The reaction yield was influenced by the presence of a phosphine ligand, pivalic acid, and base selection. With the use of 5-10 mol % catalyst, reactions of 2 with p- or m-substituted aryl bromides proceeded in moderate to good yields. Lower yields were observed with o-substituted aryl bromides. Using this method a precursor for MJL1-109-2, a known nonpeptide CRHR-1 antagonist, was successfully synthesized.

引用

页码：4716 / 4721

页数：6

共 90 条

[1] Carboxylate-Assisted Ruthenium-Catalyzed Alkyne Annulations by C-H/Het-H Bond Functionalizations [J].

Ackermann, Lutz .

ACCOUNTS OF CHEMICAL RESEARCH, 2014, 47 (02) :281-295

[2] Carboxylate-Assisted Transition-Metal-Catalyzed C-H Bond Functionalizations: Mechanism and Scope [J].

Ackermann, Lutz .

CHEMICAL REVIEWS, 2011, 111 (03) :1315-1345

[3]

[Anonymous], 2009, ANGEW CHEM-GER EDIT

[4]

Arockiam PB, 2012, CHEM REV, V112, P5879, DOI [10.1021/cr300153j, 10.1021/cr300153J]

[5] Pd-Catalysed Direct 5-Arylation of 1-Methylpyrazole with Aryl Bromides [J].

Beladhria, Anissa ;

Beydoun, Kassem ;

Ben Ammar, Hamed ;

Ben Salem, Ridha ;

Doucet, Henri .

SYNTHESIS-STUTTGART, 2011, (16) :2553-2560

[6] Chronic effects of a nonpeptide corticotropin-releasing hormone type I receptor antagonist on pituitary-adrenal function, body weight, and metabolic regulation [J].

Bornstein, SR ;

Webster, EL ;

Torpy, DJ ;

Richman, SJ ;

Mitsiades, N ;

Igel, M ;

Lewis, DB ;

Rice, KC ;

Joost, HG ;

Tsokos, M ;

Chrousos, GP .

ENDOCRINOLOGY, 1998, 139 (04) :1546-1555

[7] Development of two synthetic routes to CE-178,253, a CB1 antagonist for the treatment of obesity [J].

Brandt, Thomas A. ;

Caron, Stephane ;

Damon, David B. ;

DiBrino, Joseph ;

Ghosh, Arun ;

Griffith, David A. ;

Kedia, Sandeep ;

Ragan, John A. ;

Rose, Peter R. ;

Vanderplas, Brian C. ;

Wei, Lulin .

TETRAHEDRON, 2009, 65 (16) :3292-3304

[8]

Bremner JD, 1997, AM J PSYCHIAT, V154, P624

[9] Corticotrophin-releasing factor receptors: From molecular biology to drug design [J].

Chalmers, DT ;

Lovenberg, TW ;

Grigoriadis, DE ;

Behan, DP ;

DeSouza, EB .

TRENDS IN PHARMACOLOGICAL SCIENCES, 1996, 17 (04) :166-172

[10] EXPRESSION CLONING OF A HUMAN CORTICOTROPIN-RELEASING-FACTOR RECEPTOR [J].

CHEN, RP ;

LEWIS, KA ;

PERRIN, MH ;

VALE, WW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (19) :8967-8971

← 1 2 3 4 5 6 7 8 9 →