New disulfide route to 3-(1-piperazinyl)-1,2-benzisothiazole. Nucleus for atypical antipsychotic drugs

Organic Process Research and Development

Volumn 3, Issue 2, 1999, Pages 126-130

  Walinsky, Stanley W ^a   Fox, Darrell E ^a   Lambert, John F ^a   Sinay, Terry G ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0033470936     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op980210k     Document Type: Article

References (8)

1. (a) Howard, H. R.; Prakash, C; Seeger, T. F. Drugs Future 1994, 19, 560.
2. (b) Bench, C. J.; Lammertsma, A. A.; Dolan, R. J.; Gasby, P. M.; Warrington, S. J.; Gunn, K.; Cuddigan, M.; Turton, D. J.; Osman, S.; Frackowiak, R. S. J. Psychopharmacol. 1993, 112,308.
3. (c) O'Neill, M. F.; Palacios, J. M. Exp. Opin. Invest. Drugs 1994, 3, 1317.
4. 3-Chloro-1,2-benzisolhiazole (5) and 1,2-benzisothiazole-3(2H)-one, the synthetic precursor to 5 are strong dermal, ocular, and nasal irritants which require process containment and special handling; whereas, bis(2-cyanophenyl) disulfide did not show any dermal corrosivity or ocular or nasal irritancy. 3-(1-Piperazinyl)-1,2-benzisothiazole hydrochloride and its free base are also strong dermal, ocular, and nasal irritants; therefore, personnel should at least wear double Tyvek suits, gloves, and hood air-supply mask when handling these irritants. The use of a Rosenmund filter/dryer for the isolation of 3-(1-piperazinyl)-l,2-benzisothiazole is highly recommended.
5. Nakamura, T.; Nagata, H.; Muto, M.; Saji, I. Synthesis 1997, 871.
6. (a) Cipollina, J. A.; Ruediger, E. H.; New, J. S.; Wire, M. E.; Sheperd, T. A.; Smith, D. W.; Yevich, J. P. J. Med. Chem. 1991,34,3316.
7. (b) Böshagen, H. Chem. Ber. 1996, 99, 2566.
8. (c) Seeger, W.; Böshagen, H.; Medenuald, H. Chem. Ber. 1969, 702, 1961.