Triethylamine → 7-{4-[4-(2,3-Dichloro-phenyl)-piperazin-1-yl]-butoxy}-5-methyl-3,4-dihydro-1H-[1,8]naphthyridin-2-one

HRID 1373610Notes

Reaction equation

HRID 1373610 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.CCN(CC)CC.[CH3:23][C:24]1[C:33]2[CH2:32][CH2:31][C:30](=[O:34])[NH:29][C:28]=2[N:27]=[C:26]([O:35][CH2:36][CH2:37][CH2:38][CH:39]=O)[CH:25]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClC(Cl)C.C(Cl)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][N:13]([CH2:39][CH2:38][CH2:37][CH2:36][O:35][C:26]2[N:27]=[C:28]3[C:33]([CH2:32][CH2:31][C:30](=[O:34])[NH:29]3)=[C:24]([CH3:23])[CH:25]=2)[CH2:12][CH2:11]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 116303721-(2,3-Dichlorophenyl)piperazine hydrochlorideHCID 210733504-(4-Methyl-7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yloxy)-butyraldehyde

Product 1

HCID 115617337-{4-[4-(2,3-Dichloro-phenyl)-piperazin-1-yl]-butoxy}-5-methyl-3,4-dihydro-1H-[1,8]naphthyridin-2-oneYield 70.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent2×

Procedure

To a suspension of 1-(2,3-dichloro-phenyl)-piperazine hydrochloride (0.93 g, 3.48 mmol) in dichloroethane (10 mL) was added Et3N (0.96 mL, 6.92 mmol). The mixture was stirred for 15 min and a suspension of 4-(4-methyl-7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yloxy)-butyraldehyde (0.86 g, 3.46 mmol) in dichloroethane (5 mL) was added. After 20 min at RT, NaBH(OAc)3 (1.03 g, 4.85 mmol) was added and the reaction was stirred at room temperature for 4 h. The reaction mixture was poured into CH2Cl2 and washed with H2O, 1N citric acid, saturated NaHCO3 and brine, dried over Na2SO4 and concentrated to an oil. Et2O was added and the organics were decanted from an insoluble gum. The filtrate yielded a crystalline solid, which was collected by filtration and dried. Purification by liquid chromatography (gradient elution, 100% CHCl3 to 2% MeOH/CHCl3, Biotage 40m column) provided the title compound as a white solid (1.12 g, 2.44 mmol, 70%). MS: APCI: M+1: 463.1 (Exact Mass: 462.16).

Workup

  1. additionwas added
  2. waitAfter 20 min at RT
  3. stirringthe reaction was stirred at room temperature for 4 h
  4. washwashed with H2O, 1N citric acid, saturated NaHCO3 and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to an oil
  7. additionEt2O was added
  8. customthe organics were decanted from an insoluble gum
  9. customThe filtrate yielded a crystalline solid, which
  10. filtrationwas collected by filtration
  11. customdried
  12. customPurification
  13. washby liquid chromatography (gradient elution, 100% CHCl3 to 2% MeOH/CHCl3, Biotage 40m column)

Sources & evidence

ORD record
ord-f99058e8660f4b7ab497df16805c2368
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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