1,2-Dichloroethane → 5-(Dimethylaminocarbonyl)-2-(4-fluorobenzyl)-8-hydroxy-6-methyl-2,3,4,4a,5,6-hexahydro-2,6-naphthyridine-1,7-dione

HRID 1436885Notes

Reaction equation

HRID 1436885 reaction equation
[F:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][N:7]2[CH2:16][CH2:15][CH:14]3[C:9](=[C:10]([OH:22])[C:11](=[O:21])[N:12]([CH3:20])[CH:13]3[C:17](O)=[O:18])[C:8]2=[O:23])=[CH:4][CH:3]=1.C(Cl)CCl.Cl.[CH3:31][NH:32][CH3:33].C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C=O)C>[CH3:31][N:32]([CH3:33])[C:17]([CH:13]1[N:12]([CH3:20])[C:11](=[O:21])[C:10]([OH:22])=[C:9]2[CH:14]1[CH2:15][CH2:16][N:7]([CH2:6][C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:25][CH:24]=1)[C:8]2=[O:23])=[O:18]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 10473Dimethylamine, hydrochlorideHCID 757711-HydroxybenzotriazoleHCID 690691832-(4-Fluorobenzyl)-8-hydroxy-6-methyl-2,3,4,4a,5,6-hexahydro-2,6-naphthyridine-1,7-dione-5-carboxylic acid

Product 1

HCID 546859035-(Dimethylaminocarbonyl)-2-(4-fluorobenzyl)-8-hydroxy-6-methyl-2,3,4,4a,5,6-hexahydro-2,6-naphthyridine-1,7-dione

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(4-fluorobenzyl)-8-hydroxy-6-methyl-2,3,4,4a,5,6-hexahydro-2,6-naphthyridine-1,7-dione-5-carboxylic acid (0.012 g, 0.0.034 mol) in DMF (0.5 mL) was added EDC (0.007 g, 0.038 mmol), dimethylamine hydrochloride (0.003 g, 0.038 mmol) and HOBT (0.006 g, 0.038 mmol). After stirring at room temperature, triethylamine (0.008 g, 0.076 mmol) was added. After 2 hours, the reaction mixture was concentrated under vacuum. The residual material was partitioned between CHCl3 and water. The organic extract was dried with Na2SO4, filtered, and concentrated under vacuum. The residue was purified using reverse phase HPLC on a C18 stationary phase eluting with 15%-85% acetonitrile (0.1% TFA) in H2O (0.1% TFA) to provide the title compound. 1H NMR (400 MHz, CDCl3) δ 7.25 (m, 2H), 7.04 (t, J=8.6 Hz, 2H), 4.75 (m, 1H), 4.44 (m, 1H), 3.95 (d, J=12.3 Hz, 1H), 3.29 (m, 4H), 3.18 (s, 3H), 1.81 (m, 1H), 1.65 (s, 6H), 1.49 (m, 1H) ppm. ES MS M+1=376.

Workup

  1. concentrationthe reaction mixture was concentrated under vacuum
  2. customThe residual material was partitioned between CHCl3 and water
  3. extractionThe organic extract
  4. dry with materialwas dried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified
  8. washeluting with 15%-85% acetonitrile (0.1% TFA) in H2O (0.1% TFA)

Sources & evidence

ORD record
ord-7574c9a59be6434aab06735a449b7a55
Source dataset
uspto-grants-2009_11
Patent number
US07619086B2

Reaction notes

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