Malononitrile → HCID 53403423, compound
Reaction equation
[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[N:8][CH:9]=2)[CH2:4][CH2:3][NH:2]1.C1C2C(=CC=NC=2)C=CN=1.C(#N)CC#N.CC[O:28][C:29](CC(CC(OCC)=O)=O)=[O:30].C(C1C2C(=CN=CC=2)C=NC=1)=O>>[CH:9]1[C:10]2[C:5](=[CH:4][CH:3]=[N:2][CH:1]=2)[C:6]([C:29]([OH:30])=[O:28])=[CH:7][N:8]=1Participants
Procedure
In contrast to the 1,2,3,4-tetrahydroisoquinolines, there are rather few examples of synthetic methods for 1,2,3,4-tetrahydro-2,7-naphthyridines in the literature. One important method to prepare 1,2,3,4-tetrahydro-2,7-naphthyridine is the regio-selective catalytic reduction of 2,7-naphthyridine (Eur. J. Med. Chem. Ther. 1996, 31(11), 875-888). The synthesis of 2,7-naphthyridine and some derivatives thereof has been described in the literature. One classical route involves several steps and starts with the acid catalysed condensation of malononitrile with diethyl 1,3-acetonedicarboxylate (J. Chem. Soc. 1960, 3513-3515; see also J. Heterocycl. Chem. 1970, 7, 419-421). A slightly different route to 2,7-naphthyridine involves oxidation of 4-formyl-2,7-naphthyridine to give 2,7-naphthyridine-4-carboxylic acid followed by decarboxylation (Synthesis 1973, 46-47). A completely different method is based on the internal Diels-Alder reaction of N-(ethoxycarbonyl)-N-(but-3-ynyl)amino-methylpyrazine and gives a mixture of 1,2,3,4-tetrahydro-2,7-naphthyridine and 5,6,7,8-tetrahydro-1,7-naphthyridine after hydrolysis of the carbamate group (WO 02/064574).
Sources & evidence
- ORD record
- ord-715359d11be34825acbe2409cfae0b45
- Source dataset
- uspto-grants-2010_04
- Patent number
- US07700604B2
Reaction notes
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