4-Aminopyridine → 2H-Pyrido[4,3-d][1,3]oxazine-2,4(1H)-dione

HRID 901223Notes

Reaction equation

HRID 901223 reaction equation
NC1C=CN=CC=1.C(O[C:13]([NH:15][C:16]1[C:21]([C:22]([OH:24])=[O:23])=[CH:20][N:19]=[CH:18][CH:17]=1)=[O:14])(C)(C)C>>[NH:15]1[C:16]2[CH:17]=[CH:18][N:19]=[CH:20][C:21]=2[C:22](=[O:23])[O:24][C:13]1=[O:14]

Participants

3

Reactant 2

HCID 17274-AminopyridineHCID 221726234-{[(Tert-butoxy)carbonyl]amino}pyridine-3-carboxylic acid

Product 1

HCID 107970962H-Pyrido[4,3-d][1,3]oxazine-2,4(1H)-dione

Procedure

The starting materials for this synthesis was 4-aminopyridine which was protected by boc group and converted to 4-tert-butoxycarbonylamino-nicotinic acid, depicted as formula 35 in Scheme 15, by ortholithiation followed by quenching with dry ice. This intermediate was reacted with trichloromethyl chloroformate to yield 1H-pyrido[4,3-d][1,3]oxazine-2,4-dione, depicted by formula 36 in Scheme 15, which was then converted to 4-chloro-2-oxo-1,2-dihydro-[1,6]-naphthyridine-3-carboxylic acid ethyl ester, depicted by formula 37 in Scheme 15. The reaction of 4-chloro-2-oxo-1,2-dihydro-[1,6]-naphthyridine-3-carboxylic acid ethyl ester with piperazine-1-yl-thiophene-2-yl-methanone gave 2-oxo-4-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-1,2-dihydro-[1,6]-naphthyridin-3-carboxylic acid ethyl ester, depicted by formula 38 in Scheme 15, which was reacted with corresponding alkyl halides (R—X) to yield 1-N-substituted-2-oxo-4-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-1,2-dihydro-[1,6]-naphthyridine-3-carboxylic acid ethyl esters as shown in Scheme 15.

Workup

  1. customby quenching with dry ice
  2. customThis intermediate was reacted with trichloromethyl chloroformate

Sources & evidence

ORD record
ord-6df1ab8891444610b6942a1587d2cfdb
Source dataset
uspto-grants-2008_04
Patent number
US07361760B2

Reaction notes

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