Sodium → 1,2,3,4-Tetrahydro-1,8-naphthyridine

HRID 1385484Notes

Reaction equation

HRID 1385484 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][CH2:8][CH2:9][NH2:10])[CH:2]=1.[Na]>C1(C)C=CC=CC=1>[NH:1]1[C:2]2[C:3](=[CH:7][CH:8]=[CH:9][N:10]=2)[CH2:4][CH2:5][CH2:6]1

Participants

4

Reactant 2

HCID 5360545SodiumHCID 135575233-(Pyridin-3-yl)propan-1-amine

Product 1

HCID 130473671,2,3,4-Tetrahydro-1,8-naphthyridineYield 30%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

The final step in the process of the present invention is the cyclization of compound (II) to elaborate the final product (I). This intramolecular transformation is efficiently carried out by an optimized Chichibabin-type reaction (for a discussion of Chichibabin aminations, see H. Vorbrüggen, Adv. Heterocyclic Chem., 49, 1990, 117-192). Intramolecular nucleophilic cyclizations of 3-substituted pyridylalkylamines have previously been described. Thus, treatment of 3-(3-pyridyl)propylamine with two equivalents of sodium in boiling toluene afforded 1,2,3,4-tetrahydro-[1,8]-naphthyridine in 30% yield (E. M. Hawes and H. L. Davis, J. Heterocyclic Chem., 1973, 39-42). 1,2,3,4-Tetrahydro-3-phenyl-[1,8]-naphthyridine has been similarly prepared in 54% yield (E. M. Hawes and D. G. Wibberley, J. Chem. Soc. (C), 1966, 315-321). The substrate for the Chichibabin-reaction of the present invention has two nucleophilic amino groups presenting complicating issues of regioselectivity and intramolecular vs. intermolecular reactivity.

Workup

  1. customThis intramolecular transformation is efficiently carried out by an optimized Chichibabin-type reaction (for a discussion of Chichibabin aminations

Sources & evidence

ORD record
ord-601a743085f2488fab67910a86cd8b94
Source dataset
uspto-grants-2001_07
Patent number
US06262268B1

Reaction notes

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