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

HRID 1373592Notes

Reaction equation

HRID 1373592 reaction equation
[CH3:1][CH:2]1[C:11](=[O:12])[NH:10][C:9]2[N:8]=[C:7]([O:13][CH2:14][CH2:15][CH2:16][CH:17]=O)[CH:6]=[CH:5][C:4]=2[CH2:3]1.[Cl:19][C:20]1[C:25]([Cl:26])=[CH:24][CH:23]=[CH:22][C:21]=1[N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CO>[Cl:19][C:20]1[C:25]([Cl:26])=[CH:24][CH:23]=[CH:22][C:21]=1[N:27]1[CH2:32][CH2:31][N:30]([CH2:17][CH2:16][CH2:15][CH2:14][O:13][C:7]2[N:8]=[C:9]3[C:4]([CH2:3][CH:2]([CH3:1])[C:11](=[O:12])[NH:10]3)=[CH:5][CH:6]=2)[CH2:29][CH2:28]1

Participants

5

Reactant 3

HCID 8518331-(2,3-Dichlorophenyl)piperazineHCID 5049666Sodium triacetoxyborohydride2×HCID 210733644-(6-Methyl-7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yloxy)-butyraldehyde

Product 1

HCID 210735417-{4-[4-(2,3-Dichloro-phenyl)-piperazin-1-yl]-butoxy}-3-methyl-3,4-dihydro-1H-[1,8]naphthyridin-2-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of crude 4-(6-methyl-7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yloxy)-butyraldehyde (0.5 g, 2.0 mmol, 1.0 equiv) in anhydrous methanol (40 mL) cooled to 0° C. was added 2,3-dichlorophenylpiperazine (1.1 g, 4.0 mmol, 2.0 equiv). The mixture was stirred for 5 min and NaBH(OAc)3 (2.14 g, 10.0 mmol, 5.0 equiv) was added. The reaction mixture was brought to room temperature and stirred overnight. TLC indicated a trace amount of aldehyde was still left. More NaBH(OAc)3 was added and stirring continued for one more hour. TLC indicated the reaction was complete. The reaction mixture was concentrated to dryness. The resultant pale green residue was dissolved in ethyl acetate and washed with 0.5 N HCl (1×10 mL), saturated NaHCO3 solution (1×10 mL) and brine. The organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography (silica gel, 2% MeOH/CH2Cl2) to afford the title compound as a colorless viscous material (0.63 g, 75% over 2 steps). The enantiomers were separated by chiral HPLC (Chiralpak AD, 40:60 Hexane/EtOH) to give the enantiomers D6a and D6b. MS: APCI: M+1: 463.1 (Exact Mass: 462.16).

Workup

  1. customwas brought to room temperature
  2. stirringstirred overnight
  3. waitwas still left
  4. stirringstirring
  5. concentrationThe reaction mixture was concentrated to dryness
  6. dissolutionThe resultant pale green residue was dissolved in ethyl acetate
  7. washwashed with 0.5 N HCl (1×10 mL), saturated NaHCO3 solution (1×10 mL) and brine
  8. dry with materialThe organic layer was dried over Na2SO4
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography (silica gel, 2% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-587fe230e17e4ad2a87925bf93050294
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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