2-Thiophenecarbonyl chloride → 1-Benzyl-2-oxo-4-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-1,2-dihydro-[1,8]-naphthyridine-3-carbonitrile

HRID 901235Notes

Reaction equation

HRID 901235 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6](Cl)=[O:7].[CH2:9]([N:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][N:24]=2)[C:19]([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[C:18]([C:32]#[N:33])[C:17]1=[O:34])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>N1C=CC=CC=1>[CH2:9]([N:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][N:24]=2)[C:19]([N:26]2[CH2:31][CH2:30][N:29]([C:6]([C:2]3[S:1][CH:5]=[CH:4][CH:3]=3)=[O:7])[CH2:28][CH2:27]2)=[C:18]([C:32]#[N:33])[C:17]1=[O:34])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

4

Reactant 2

HCID 789282-Thiophenecarbonyl chlorideHCID 596995621-Benzyl-2-oxo-4-piperazin-1-yl-1,2-dihydro-[1,8]-naphthyridine-3-carbonitrile

Product 1

HCID 112248371-Benzyl-2-oxo-4-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-1,2-dihydro-[1,8]-naphthyridine-3-carbonitrileYield 59.9%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

2-Thiophene carbonyl chloride (0.16 mL, 1.5 mmol) was added to a stirred solution of 1-benzyl-2-oxo-4-piperazin-1-yl-1,2-dihydro-[1,8]-naphthyridine-3-carbonitrile (9) (345 mg, 1 mmol) in pyridine at 0° C. The solution was allowed to come at room temperature and further stirred overnight at room temperature. The solution was poured into ice water and the solids formed were filtered, washed by water, and dried. The crude product was purified by flash chromatography eluting with linear gradients of 0-3% MeOH in CH2Cl2 to yield 273 mg (45%) of 1-benzyl-2-oxo-4-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-1,2-dihydro-[1,8]-naphthyridine-3-carbonitrile (10) as white solids. MP: 263° C.; 1H-NMR (DMSO-d6): δ 3.75 (m, 4H), 3.94 (m, 4H), 5.58 (s, 2H), 7.15 (dd, J=3.5, 4.8 Hz, 1H), 7.19-7.29 (m, 5H), 7.40 (dd, J=4.8, 8.0 Hz, 1H), 7.52 (dd, J=4.0, 5.2 Hz, 1H), 8.35 (dd, J=1.6, 8.0 Hz, 1H), 8.72 (dd, J=1.6, 8.0 Hz, 1H); EIMS: 456 (M+1). Anal. C25H21N5O2S (C,H,N).

Workup

  1. customthe solids formed
  2. filtrationwere filtered
  3. washwashed by water
  4. customdried
  5. customThe crude product was purified by flash chromatography
  6. washeluting with linear gradients of 0-3% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-22f49777ffbd4d92bf7e6edf45b1ea16
Source dataset
uspto-grants-2008_04
Patent number
US07361760B2

Reaction notes

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