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

HRID 1373608Notes

Reaction equation

HRID 1373608 reaction equation
[Br:1][C:2]1[C:3]([O:13][CH2:14][CH2:15][CH2:16][CH:17]=O)=[N:4][C:5]2[NH:6][C:7](=[O:12])[CH2:8][CH2:9][C:10]=2[CH:11]=1.Cl.[C:20]1([N:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][CH:21]=1.CCN(CC)CC.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[Br:1][C:2]1[CH:11]=[C:10]2[C:5](=[N:4][C:3]=1[O:13][CH2:14][CH2:15][CH2:16][CH2:17][N:33]1[CH2:32][CH2:31][N:30]([C:20]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=[CH:22][CH:21]=3)[CH2:35][CH2:34]1)[NH:6][C:7](=[O:12])[CH2:8][CH2:9]2

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27373911-(1-Naphthyl)piperazine hydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 210733374-(3-Bromo-7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yloxy)-butyraldehyde

Product 1

HCID 210734506-Bromo-7-[4-(4-naphthalen-1-yl-piperazin-1-yl)-butoxy]-3,4-dihydro-1H-[1,8]naphthyridin-2-oneYield 76%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 4-(3-bromo-7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yloxy)-butyraldehyde (1.11 g, approx. 3.54 mmol, crude) in DCE (17 mL) was added 1-naphthalen-1-yl-piperazine hydrochloride (0.882 g, 3.54 mmol) followed by Et3N (1.0 mL, 7.1 mmol). The solution was stirred for 15 min and NaBH(OAc)3 (1.05 g, 4.96 mmol) was added as a powder. The reaction was stirred at room temperature for 2 h and quenched with saturated NaHCO3 and H2O. The mixture was extracted with EtOAc. The organic layer was washed with saturated NaHCO3, H2O and brine, dried over Na2SO4 and concentrated. Purification by liquid chromatography (4% MeOH/CH2Cl2) afforded the title compound as an off-white foam (1.37 g, 2.69 mmol, 76%). The HCl salt was formed by dissolving the title compound (138 mg, 0.27 mmol) in Et2O/CH2Cl2 followed by the addition of 1N HCl in Et2O (0.3 mL). The resulting white precipitate was collected by filtration, washed with Et2O and dried to give a white solid (125 mg). MS: APCI: M+1: 509.1, 511.1 (Exact Mass: 508.15).

Workup

  1. stirringThe reaction was stirred at room temperature for 2 h
  2. customquenched with saturated NaHCO3 and H2O
  3. extractionThe mixture was extracted with EtOAc
  4. washThe organic layer was washed with saturated NaHCO3, H2O and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customPurification by liquid chromatography (4% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-754445f2967545f3bc06ec4df190915e
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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