2002
DOI: 10.1021/op020066+
|View full text |Cite
|
Sign up to set email alerts
|

A New Approach to the Rapid Parallel Development of Four Neurokinin Antagonists. Part 3. Assembly of Neurokinin Antagonists

Abstract: Four neurokinin antagonists were assembled using a rapid parallel development approach. Research Department processes were scaled up if process safety and robustness were not compromised. Using this approach, 1 kg of each compound was rapidly delivered for clinical trials.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1

Citation Types

0
23
0

Year Published

2002
2002
2022
2022

Publication Types

Select...
5
2
1

Relationship

1
7

Authors

Journals

citations
Cited by 17 publications
(23 citation statements)
references
References 7 publications
0
23
0
Order By: Relevance
“…99 The reaction solvent was changed from methanol to dichloromethane to avoid competing formation of dimethyl acetal byproduct and to allow telescoping the two steps to form ZD6021. The procedure was very effective to produce 162 crude in 76% overall yield at multi-kilogram scale (Scheme 65).…”
Section: Via Amine Boranesmentioning
confidence: 99%
See 1 more Smart Citation
“…99 The reaction solvent was changed from methanol to dichloromethane to avoid competing formation of dimethyl acetal byproduct and to allow telescoping the two steps to form ZD6021. The procedure was very effective to produce 162 crude in 76% overall yield at multi-kilogram scale (Scheme 65).…”
Section: Via Amine Boranesmentioning
confidence: 99%
“…To prepare an intermediate for the synthesis of neurokinin antagonists, Parker and co-workers replaced hazardous sodium cyanoborohydride with PYB in a reductive amination . The reaction solvent was changed from methanol to dichloromethane to avoid competing formation of dimethyl acetal byproduct and to allow telescoping the two steps to form ZD6021.…”
Section: 41 Via Amine Boranesmentioning
confidence: 99%
“…An overview of the strategy was given and illustrated by examples taken from across the neurokinin (NK) project . This contribution and the next discuss in more detail the experiences of manufacture of key fragments of molecules required for the NK programme and seek to assess the application and success of this new approach in more detail.
…”
Section: Introductionmentioning
confidence: 99%
“…Another class of reducing agents that is routinely utilized for reductive amination is amine boranes, such as pyridine-borane, 2-picoline-borane, , dimethylamine-borane, N -isopropyl- N -methyl- tert -butylamine-borane, 5-ethyl-2-methylpyridine-borane, and benzylamine-borane . With these reagents, an equivalent of the amine from the reductant remains in the product mixture, necessitating their difficult separation from the desired product amine.…”
mentioning
confidence: 99%
“…Next, the solvent-free reductive amination was evaluated with other amine-boranes that are commonly used for reductive amination, such as pyridine-borane (5), 2-picolineborane (6), and t-butylamine-borane (7) as well as several inhouse synthesized 31 amine-boranes, such as triethylamineborane (8), piperidine-borane (9), morpholine-borane (10), benzylamine-borane (11), and cyclohexylamine-borane (12). The results summarized in Table 1 reveal very unsatisfactory yields with 2-picoline-borane (entry 3) and t-butylamineborane (entry 4).…”
mentioning
confidence: 99%