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

HRID 1373540Notes

Reaction equation

HRID 1373540 reaction equation
[CH2:1]([C:3]1[N:8]=[C:7]([N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=1)[CH3:2].CCN(CC)CC.[O:22]=[C:23]1[NH:32][C:31]2[N:30]=[C:29]([O:33][CH2:34][CH2:35][CH2:36][CH:37]=O)[CH:28]=[CH:27][C:26]=2[CH2:25][CH2:24]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClC(Cl)C>[CH2:1]([C:3]1[N:8]=[C:7]([N:9]2[CH2:10][CH2:11][N:12]([CH2:37][CH2:36][CH2:35][CH2:34][O:33][C:29]3[N:30]=[C:31]4[C:26]([CH2:25][CH2:24][C:23](=[O:22])[NH:32]4)=[CH:27][CH:28]=3)[CH2:13][CH2:14]2)[CH:6]=[CH:5][CH:4]=1)[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 210731761-(6-Ethylpyridin-2-YL)piperazineHCID 210733774-((7-Oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)oxy)butanal

Product 1

HCID 210737297-{4-[4-(6-Ethyl-pyridin-2-yl)-piperazin-1-yl]-butoxy}-3,4-dihydro-1H-[1,8]naphthyridin-2-oneYield 47.4%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent2×

Procedure

To a solution of 1-(6-ethyl-pyridin-2-yl)-piperazine (0.41 g, 2.13 mmol) in dichloroethane (15 mL) was added Et3N (0.22 g, 2.13 mmol) and the mixture was stirred for 5 min. 4-(7-Oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yloxy)-butyraldehyde (0.50 g, 2.13 mmol) was added as a solution in dichloroethane (3 mL) and the mixture was stirred at room temperature for 15 min. NaBH(OAc)3 (0.63 g, 3.00 mmol) was added as a solid and the reaction was stirred at room temperature for 2 h. The reaction was quenched with saturated NaHCO3 and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4 and concentrated. Purification by liquid chromatography (Biotage 40M, gradient elution 100% CH2Cl2 to 99% CH2Cl2/MeOH) afforded the title compound as a sticky white foam (413 mg, 1.01 mmol, 47%). The foam was dissolved in Et2O and treated with anhydrous HCl gas to give a white precipitate. The mixture was filtered and dried to give a white powder (287 mg). MS: APCI: M+1: 410.3 (Exact Mass: 409.25).

Workup

  1. stirringthe mixture was stirred at room temperature for 15 min
  2. stirringthe reaction was stirred at room temperature for 2 h
  3. customThe reaction was quenched with saturated NaHCO3
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customPurification
  9. washby liquid chromatography (Biotage 40M, gradient elution 100% CH2Cl2 to 99% CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-d92466c58b694a078d0c6d65aa7ec79f
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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