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

HRID 1373593Notes

Reaction equation

HRID 1373593 reaction equation
[CH3:1][C:2]1[C:3]2[CH:4]=[CH:5][C:6]([O:14][CH2:15][CH2:16][CH2:17][CH:18]=O)=[N:7][C:8]=2[NH:9][C:10](=[O:13])[C:11]=1[CH3:12].Cl.[Cl:21][C:22]1[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:23]=1[N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.C(N(CC)CC)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClC(Cl)C.O>[Cl:21][C:22]1[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:23]=1[N:29]1[CH2:34][CH2:33][N:32]([CH2:18][CH2:17][CH2:16][CH2:15][O:14][C:6]2[N:7]=[C:8]3[C:3]([C:2]([CH3:1])=[C:11]([CH3:12])[C:10](=[O:13])[NH:9]3)=[CH:4][CH:5]=2)[CH2:31][CH2:30]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 116303721-(2,3-Dichlorophenyl)piperazine hydrochlorideHCID 21073354HCID 21073354, compound

Product 1

HCID 210735387-{4-[4-(2,3-Dichloro-phenyl)-piperazin-1-yl]-butoxy}-3,4-dimethyl-1H-[1,8]naphthyridin-2-oneYield 68.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 63651,1-DichloroethaneSolvent

Procedure

The crude 4-(5,6-dimethyl-7-oxo-7,8-dihydro-[1,8]naphthyridin-2-yloxy)-butyraldehyde (100 mg, 0.38 mmol) is dissolved in dichloroethane (7 mL) and 1-(2,3-dichlorophenyl)piperazine monohydrochloride (112 mg, 0.42 mmol) is added, followed by triethylamine (39 mg, 0.05 mL, 1.14 mmol). The mixture is stirred for 5 minutes and NaBH(OAc)3 (81 mg, 0.38 mmol) is added. The mixture is stirred at room temperature for 1 hour and water (5 mL) is added. The organic layer is separated, washed with brine (10 mL), dried over Na2SO4, filtered and concentrated under vacuum. The crude solid is purified by column chromatography (1:9 methanol/ethyl acetate) to yield the title compound (123 mg, 68%) as a white solid. mp 161–163° C., 1H NMR (400 MHz, CDCl3) δ 8.98 (br s, 1H), 7.80 (d, 1H), 7.20–7.10 (m, 2H), 7.00–6.90 (m, 1H), 6.60 (d, 1H), 4.20 (t, 2H), 3.15–3.00 (m, 4H), 2.75–2.60 (m, 4H), 2.50 (t, 2H), 2.40 (s, 3H), 2.20 (s, 3H), 1.85–1.60 (m, 4H), MS ES+ 474.76 (M)+ (Exact Mass: 474.16).

Workup

  1. stirringThe mixture is stirred at room temperature for 1 hour
  2. customThe organic layer is separated
  3. washwashed with brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe crude solid is purified by column chromatography (1:9 methanol/ethyl acetate)

Sources & evidence

ORD record
ord-742d207ea0a74e3eab8a1a480303b6e5
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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