Ammonia → Methyl 6-cyanonaphthalene-2-carboxylate

HRID 1351705Notes

Reaction equation

HRID 1351705 reaction equation
C1(C(O)=O)C2C(=CC=CC=2)C=CC=1.S(Cl)(Cl)=O.N.[CH3:19][O:20][C:21]([C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[C:28]([C:33](=O)[NH2:34])[CH:29]=2)[CH:24]=1)=[O:22].ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl.COP(OC)(OC)=O>[CH3:19][O:20][C:21]([C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[C:28]([C:33]#[N:34])[CH:29]=2)[CH:24]=1)=[O:22]

Participants

8

Reactant 5

HCID 222AmmoniaHCID 68471-Naphthoic acidHCID 24386Thionyl ChlorideHCID 94429TriphosgeneHCID 12052259Methyl 6-carbamoylnaphthalene-2-carboxylate

Product 1

HCID 12433083Methyl 6-cyanonaphthalene-2-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 10541Trimethyl PhosphateSolvent

Procedure

Compounds of formula II, where T is a bond, B is H, each of-e and g is C—H, f is a bond, V is a substituted carbonyl group, and Z′ is NH can be prepared as follows. Hydrolysis of naphthalene-2,6 dicarboxylic acid dimethyl ester with one equivalent of a base such as KOH, followed by acidification of the product with an acid such as HCl, affords the naphthalene mono carboxylic acid. After conversion of the carboxylic acid to an acid chloride with a reagent such as thionyl chloride and subsequent reaction with ammonia in methylene chloride, the resulting 6-carbamoyl-naphthalene-2-carboxylic acid methyl ester is reacted with triphosgene in trimethylphosphate to provide 6-cyano-naphthalene-2-carboxylic acid methyl ester. Hydrolysis of the ester with LiOH in aqueous THF solution, followed by reaction with thionyl chloride, affords 6-cyano-naphthalene-2-carbonyl chloride, which can then be coupled with alcohols or amines to provide compounds of the formula XX. The amidine, hydroxyamidine, or aminoamidine groups can be obtained from the nitrile as described previously to afford compounds the formula XXI, where R19 is H, and R22 is H, alkyl, OH, or NH2, and V is an alkylaminocarbonyl, dialkylaminocarbonyl, cycloalkylaminocarbonyl, aralkylaminocarbonyl, arylaminocarbonyl, heterocyclylaminocarbonyl, alkoxycarbonyl, cycloalkoxycarbonyl, aralkoxycarbonyl, aryloxycarbonyl, heterocyclyloxycarbonyl, or heteroaralkyloxycarbonyl.

Sources & evidence

ORD record
ord-d564e31234f9403e8ada749e427876b2
Source dataset
uspto-grants-2007_05
Patent number
US07217794B2

Reaction notes

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