Triethylamine → 6-Methyl-7-[4-(4-naphthalen-1-yl-piperazin-1-yl)-butoxy]-3,4-dihydro-1H-[1,8]naphthyridin-2-one

HRID 1373602Notes

Reaction equation

HRID 1373602 reaction equation
CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.O[CH2:24][CH2:25][CH2:26][CH2:27][O:28][C:29]1[N:38]=[C:37]2[C:32]([CH2:33][CH2:34][C:35](=[O:39])[NH:36]2)=[CH:31][C:30]=1[CH3:40].C([O-])(O)=O.[Na+].[O-]S([O-])(=S)=O.[Na+].[Na+].Cl.[C:54]1([N:64]2[CH2:69][CH2:68][NH:67][CH2:66][CH2:65]2)[C:63]2[C:58](=[CH:59][CH:60]=[CH:61][CH:62]=2)[CH:57]=[CH:56][CH:55]=1.CCN(CC)CC.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[CH3:40][C:30]1[CH:31]=[C:32]2[C:37](=[N:38][C:29]=1[O:28][CH2:27][CH2:26][CH2:25][CH2:24][N:67]1[CH2:66][CH2:65][N:64]([C:54]3[C:63]4[C:58](=[CH:59][CH:60]=[CH:61][CH:62]=4)[CH:57]=[CH:56][CH:55]=3)[CH2:69][CH2:68]1)[NH:36][C:35](=[O:39])[CH2:34][CH2:33]2

Participants

9

Reactant 7

HCID 8471TriethylamineHCID 24477Sodium ThiosulfateHCID 159087TriacetoxyperiodinaneHCID 516892Sodium BicarbonateHCID 27373911-(1-Naphthyl)piperazine hydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 210738567-(4-hydroxy-butoxy)-6-methyl-3,4-dihydro-1H-[1,8]naphthyridin-2-one

Product 1

HCID 210734676-Methyl-7-[4-(4-naphthalen-1-yl-piperazin-1-yl)-butoxy]-3,4-dihydro-1H-[1,8]naphthyridin-2-oneYield 41%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a clear solution of Dess-Martin reagent (1.40 g, 3.3 mmol, 1.3 equiv) in CH2Cl2 (200 mL) was added 7-(4-hydroxy-butoxy)-6-methyl-3,4-dihydro-1H-[1,8]naphthyridin-2-one (0.55 g, 2.2 mmol, 1.0 equiv) and the mixture was stirred at room temperature for 4 hours. TLC confirmed the completion of the reaction. The reaction mixture was diluted with CH2Cl2 and poured into a saturated solution of NaHCO3 containing Na2S2O3 (3.0 g). The mixture was stirred and the organic layer was separated. The aqueous layer was extracted with CH2Cl2 (2×30 mL) and the combined organic layer was dried over Na2SO4 and concentrated. The crude aldehyde was dissolved in DCE and 1-naphthalen-1-yl-piperazine monohydrochloride (0.76 g, 3.08 mmol, 1.4 equiv), Et3N (0.5 mL, 1.7 equiv) and NaBH(OAc)3 (0.65 g, 3.08 mmol, 1.4 equiv) were added. The reaction mixture was stirred for 1 hour, diluted with CH2Cl2 and washed with saturated NaHCO3 and brine. The organic layer was dried over Na2SO4 and concentrated. Purification of the residue by column chromatography (5% MeOH/EtOAc) gave the title compound as a white solid (0.40 g, 41%). mp: 76–78° C.; 1H NMR: (400 MHz, CDCl3) δ 8.22 (d, 1H), 7.85 (d, 1H), 7.58–7.38 (m, 5H), 7.25 (s, 1H), 7.05 (d, 1H), 4.25 (t, 2H), 3.30–3.10 (br s, 4H), 2.82–2.65 (m, 4H), 2.65–2.45 (m, 4H), 2.15 (s, 3H), 1.88–1.35 (m, 6H). MS: ES+ 445.41 (M+H)+, exact mass: 444.25.

Workup

  1. customthe completion of the reaction
  2. stirringThe mixture was stirred
  3. customthe organic layer was separated
  4. extractionThe aqueous layer was extracted with CH2Cl2 (2×30 mL)
  5. dry with materialthe combined organic layer was dried over Na2SO4
  6. concentrationconcentrated
  7. dissolutionThe crude aldehyde was dissolved in DCE
  8. stirringThe reaction mixture was stirred for 1 hour
  9. washwashed with saturated NaHCO3 and brine
  10. dry with materialThe organic layer was dried over Na2SO4
  11. concentrationconcentrated
  12. customPurification of the residue by column chromatography (5% MeOH/EtOAc)

Sources & evidence

ORD record
ord-bd74038d14cf42a3ad34140e3e20ea75
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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