Helvetica Chimica Acta, 2003, 86(7), 2610 - 2619
(
http://angelfire.lycos.com/scifi2/lego/journals/trachsel2.pdf)
DOI:
10.1002/hlca.200390210
Synthesis of Novel (Phenylalkyl)amines for the Investigation of Structure-Activity Relationships. Part 2.
4-Thio-Substituted [2-(2,5-Dimethoxyphenyl)ethyl]amines (=2,5-Dimethoxybenzeneethanamines)
AbstractThe 4-substituted [2-(2,5-dimethoxyphenyl)ethyl]amines (=2,5-dimethoxybenzeneethanamines) and its -methyl analogs are known to act as potent 5-HT
2A/C ligands, which have, depending on their 4-substituent, agonistic or antagonistic character. Generally, compounds with a small lipophilic substituent typically are agonists and those with a larger lipophilic substituent predominantly antagonists or at least partial agonists. Since little is known about the transition and more information is needed about the structural requirements of the 4-substituent to control the functional activity, 12 novel 4-thio-substituted [2-(2,5-dimethoxyphenyl)ethyl]amines were synthesized and spectroscopically characterized. Thus 2,5-dimethoxybenzenethiol (7) was converted to the thioether derivatives 8a-l with several alkyl, fluoroalkyl, alkenyl, and benzyl halides. Subsequent Vilsmeier-formylation afforded the benzaldehydes 9a-l, condensation with MeNO
2 the nitroethenyl derivatives 10a-l, and reduction with AlH
3 the desired (2-phenylethyl)amines 11a-l.
Helvetica Chimica Acta, 2003, 86(, 2754 - 2759
(
http://angelfire.lycos.com/scifi2/lego/journals/trachsel3.pdf)
DOI:
10.1002/hlca.200390224
The DOI is not working although it is from the publisher's homepage.
Synthesis of Novel (Phenylalkyl)amines for the Investigation of StructureActivity Relationships, Part 3
4-Ethynyl-2,5-dimethoxyphenethylamine (=4-Ethynyl-2,5-dimethoxybenzeneethanamine; 2C-YN)AbstractAn easy and efficient pathway for the preparation of 4-ethynyl-2,5-dimethoxyphenethylamine (=4-ethynyl-2,5-dimethoxybenzeneethanamine; 2C-YN; 1) was developed, an ethynyl analogue of the potent 5-HT
2A/C agonists, e.g., 4-iodo-2,5-dimethoxy-amphetamine (DOI; 2b). The ethynyl moiety was introduced by a Pd-catalyzed Sonogashira reaction of (trimethylsilyl)ethyne with N-(trifluoroacetyl)-protected 4-iodo-2,5-dimethoxyphenethylamine (7) in almost quantitative yield within only 1 h. Removal of the Me
3Si group was accomplished with Bu
4NF. Final N-deprotection by NaOH treatment afforded the novel phenethylamine 1 in an overall yield of 88%.