Triethylamine → 7-{4-[4-(2,3-Dichloro-phenyl)-piperazin-1-yl]-butoxy}-6-fluoro-3,4-dihydro-1H-[1,8]naphthyridin-2-one

HRID 1373603Notes

Reaction equation

HRID 1373603 reaction equation
Cl.[Cl:2][C:3]1[C:8]([Cl:9])=[CH:7][CH:6]=[CH:5][C:4]=1[N:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.C(N(CC)CC)C.[F:23][C:24]1[C:25]([O:35][CH2:36][CH2:37][CH2:38][CH:39]=O)=[N:26][C:27]2[NH:28][C:29](=[O:34])[CH2:30][CH2:31][C:32]=2[CH:33]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CCOC(C)=O.ClC(Cl)C>ClCCCl>[Cl:2][C:3]1[C:8]([Cl:9])=[CH:7][CH:6]=[CH:5][C:4]=1[N:10]1[CH2:15][CH2:14][N:13]([CH2:39][CH2:38][CH2:37][CH2:36][O:35][C:25]2[N:26]=[C:27]3[C:32]([CH2:31][CH2:30][C:29](=[O:34])[NH:28]3)=[CH:33][C:24]=2[F:23])[CH2:12][CH2:11]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 116303721-(2,3-Dichlorophenyl)piperazine hydrochlorideHCID 210733404-(3-Fluoro-7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yloxy)-butyraldehydeHCID 21873757Dichloroethane ethyl acetate

Product 1

HCID 210735477-{4-[4-(2,3-Dichloro-phenyl)-piperazin-1-yl]-butoxy}-6-fluoro-3,4-dihydro-1H-[1,8]naphthyridin-2-oneYield 53%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

To a suspension of 1-(2,3-dichloro-phenyl)-piperazine hydrochloride (0.80 g, 3.0 mmol) in 1,2-dichloroethane (10 mL) was added triethylamine (0.61 mL, 6.0 mmol). The mixture was stirred for 30 min at room temperature and 4-(3-fluoro-7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yloxy)-butyraldehyde (0.76 g, 3.0 mmol) was added as a suspension in 1,2-dichloroethane (5 mL). The mixture was stirred for 30 min and NaBH(OAc)3 (0.89 g, 4.2 mmol) was added as a solid. The reaction was stirred at room temperature for 4 h. The mixture was poured into EtOAc/dichloroethane and washed with saturated NaHCO3 and brine. The organic layer was washed with aqueous citric acid (pH 4.5) and brine, dried over Na2SO4 and concentrated to a slurry. Et2O was added and the solid was collected by filtration. Purification by liquid chromatography (Biotage 40S, gradient of CH2Cl2 to 10% MeOH/CHCl3) gave the title compound as a white solid (738 mg, 1.58 mmol, 53%). MS: APCI: M+1: 467.3 (Exact Mass: 466.13).

Workup

  1. stirringThe mixture was stirred for 30 min
  2. stirringThe reaction was stirred at room temperature for 4 h
  3. washwashed with saturated NaHCO3 and brine
  4. washThe organic layer was washed with aqueous citric acid (pH 4.5) and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to a slurry
  7. additionEt2O was added
  8. filtrationthe solid was collected by filtration
  9. customPurification by liquid chromatography (Biotage 40S, gradient of CH2Cl2 to 10% MeOH/CHCl3)

Sources & evidence

ORD record
ord-2e5c0153cca34b6fb0b69a05bf41e001
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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