Triethylamine → 3-Fluoro-7-[4-(4-naphthalen-1-yl-piperazin-1-yl)-butoxy]-1h-[1,8]naphthyridin-2-one

HRID 1373596Notes

Reaction equation

HRID 1373596 reaction equation
CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[F:23][C:24]1[C:25](=[O:40])[NH:26][C:27]2[C:32]([CH:33]=1)=[CH:31][CH:30]=[C:29]([O:34][CH2:35][CH2:36][CH2:37][CH2:38]O)[N:28]=2.[O-]S([O-])(=S)=O.[Na+].[Na+].Cl.[C:49]1([N:59]2[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]2)[C:58]2[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=2)[CH:52]=[CH:51][CH:50]=1.CCN(CC)CC.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.C1COCC1.CCOCC.ClCCCl.CS(C)=O>[F:23][C:24]1[C:25](=[O:40])[NH:26][C:27]2[C:32]([CH:33]=1)=[CH:31][CH:30]=[C:29]([O:34][CH2:35][CH2:36][CH2:37][CH2:38][N:62]1[CH2:61][CH2:60][N:59]([C:49]3[C:58]4[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=4)[CH:52]=[CH:51][CH:50]=3)[CH2:64][CH2:63]1)[N:28]=2

Participants

12

Reactant 6

HCID 8471TriethylamineHCID 24477Sodium ThiosulfateHCID 159087TriacetoxyperiodinaneHCID 27373911-(1-Naphthyl)piperazine hydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 210733033-Fluoro-7-(4-hydroxy-butoxy)-1h-[1,8]naphthyridin-2-one

Product 1

HCID 210733023-Fluoro-7-[4-(4-naphthalen-1-yl-piperazin-1-yl)-butoxy]-1h-[1,8]naphthyridin-2-oneYield 64.2%

Reagents, catalysts & solvents 5

HCID 111,2-DichloroethaneSolventHCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of Dess-Martin periodinane (0.79 g, 1.86 mmol, 1.2 eq) in CH2Cl2 (20 mL) was added a solution of 3-fluoro-7-(4-hydroxy-butoxy)-1H-[1,8]naphthyridin-2-one (0.39 g, 1.5 mmol) in THF (6 mL)/DMSO (2 mL). The mixture was stirred at room temperature for 1.5 h. The reaction mixture was diluted with Et2O (100 mL) and quenched with aqueous NaHCO3 (20 mL) containing Na2S2O3 (1.66 g, 10.5 mmol, 7 eq). After extraction with Et2O (3×40 mL), the combined organic layer was washed with brine (20 mL), dried over Na2SO4 and concentrated to give the crude aldehyde as a pale yellow solid. To a solution of the aldehyde in 1,2-dichloroethane (20 mL) was added 1-naphthalen-1-yl-piperazine monohydrochloride (0.522 g, 2.1 mmol, 1.4 eq), Et3N (0.38 mL, 2.85 mmol, 1.9 eq) and NaBH(OAc)3 (0.445 g, 2.1 mmol, 1.4 eq). The mixture was stirred at room temperature for 1 h and quenched with water and saturated NaHCO3. After extraction with CH2Cl2 (3×50 mL), the combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography (3% MeOH/CH2Cl2) to give the title compound (430 mg, 62% in two steps). 1H NMR (400 MHz, δ ppm): 12.60 (br s, 1H), 8.10 (d, J=6.0 Hz, 1H), 8.00 (d, J=7.2 Hz, 1H), 7.85 (m, 2H), 7.60 (d, J=6.0 Hz, 1H), 7.50 (m, 2H), 7.40 (d, J=6.0 Hz, 1H), 7.10 (d, J=6.0 Hz, 1H), 6.75 (d, J=7.0 Hz, 1H), 4.35 (t, J=4.0 Hz, 2H), 3.00 (br s, 4H), 2.60 (br s, 4H), 2.40 (t, J=3.8 Hz, 2H), 1.80 (m, 2H), 1.60 (m, 2H); 19F NMR: −140 ppm; MS: 447 (M+H)+ (Exact Mass: 446.21).

Workup

  1. customquenched with aqueous NaHCO3 (20 mL)
  2. extractionAfter extraction with Et2O (3×40 mL)
  3. washthe combined organic layer was washed with brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customto give the crude aldehyde as a pale yellow solid
  7. stirringThe mixture was stirred at room temperature for 1 h
  8. customquenched with water and saturated NaHCO3
  9. extractionAfter extraction with CH2Cl2 (3×50 mL)
  10. dry with materialthe combined organic layer was dried over Na2SO4
  11. concentrationconcentrated
  12. customThe residue was purified by column chromatography (3% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-861c51b4f18f4e06bade8f18e621456e
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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