US 7,321,042 B2
Process for preparing N-substituted 3-β-aminonortropanes
Rainer Sobotta, Ingelheim (Germany); and Hans-Peter Ignatow, Ingelheim (Germany)
Assigned to Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim (Germany)
Filed on Oct. 04, 2004, as Appl. No. 10/958,047.
Claims priority of application No. 103 48 112 (DE), filed on Oct. 16, 2003; and application No. 10 2004 013 227 (DE), filed on Mar. 18, 2004.
Prior Publication US 2005/0096346 A1, May 05, 2005
Int. Cl. C07D 451/02 (2006.01)
U.S. Cl. 546—124 7 Claims
 
1. A process for preparing N-substituted 3β-aminonortropanes of formula I or an acid addition salt thereof,

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wherein
R1 denotes an optionally substituted group selected from the group consisting of C1-C8-alkyl, C2-C8-alkenyl, C3-C8-cycloalkyl and C6-C10-aryl-C1-C8-alkyl,
wherein either
(a) a corresponding 3-oxonortropane of formula IIA

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 is reacted with an arylmethylamine of formula IIIA
H2N—CH2—Ar  (IIIA)
 wherein
 Ar denotes an optionally substituted phenyl group or an optionally substituted 5- or 6-membered heteroaromatic group with at least one heteroatom selected from the group N, O and S; or
(b) a corresponding 3α-aminonortropane of formula IIB

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 is reacted with an arylaldehyde of formula IIIB
O═CH—Ar  (IIIB);
converting the resulting imine of formulae IVA prepared in option (a) or IVB prepared in option (b)

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to the thermodynamically stable compound of formula V in the presence of a base

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which is then hydrolysed in the presence of an acid to obtain the compound of formula I, which may be optionally converted into an acid addition salt.