Sodium triacetoxyborohydride → 7-{4-[4-(2-Trifluoromethyl-3H-benzoimidazol-4-yl)-piperazin-1-yl]-butoxy}-3,4-dihydro-1H-[1,8]naphthyridin-2-one

HRID 1373640Notes

Reaction equation

HRID 1373640 reaction equation
[O:1]=[C:2]1[NH:11][C:10]2[N:9]=[C:8]([O:12][CH2:13][CH2:14][CH2:15][CH:16]=O)[CH:7]=[CH:6][C:5]=2[CH2:4][CH2:3]1.[N:18]1([C:24]2[C:32]3[N:31]=[C:30]([C:33]([F:36])([F:35])[F:34])[NH:29][C:28]=3[CH:27]=[CH:26][CH:25]=2)[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClC(Cl)C.C(OCC)(=O)C>[F:36][C:33]([F:34])([F:35])[C:30]1[NH:31][C:32]2[C:24]([N:18]3[CH2:19][CH2:20][N:21]([CH2:16][CH2:15][CH2:14][CH2:13][O:12][C:8]4[N:9]=[C:10]5[C:5]([CH2:4][CH2:3][C:2](=[O:1])[NH:11]5)=[CH:6][CH:7]=4)[CH2:22][CH2:23]3)=[CH:25][CH:26]=[CH:27][C:28]=2[N:29]=1

Participants

6

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 184141074-(piperazin-1-yl)-2-(trifluoromethyl)-1H-benzo[d]imidazoleHCID 210733774-((7-Oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)oxy)butanal

Product 1

HCID 1785156567-{4-[4-(2-Trifluoromethyl-3H-benzoimidazol-4-yl)-piperazin-1-yl]-butoxy}-3,4-dihydro-1H-[1,8]naphthyridin-2-oneYield 35.7%

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 4-(7-oxo-5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yloxy)-butyraldehyde (0.297 g, 1.266 mmol, 1.32 eq) and 4-piperazin-1-yl-2-trifluoromethyl-1H-benzoimidazole (0.258 g, 0.953 mmol, 1 eq) in dichloroethane (5 mL) was added NaBH(OAc)3 (0.723 g, 3.413 mmol, 3.58 eq). The slurry was allowed to stir overnight at room temperature (18 h). Analysis by HPLC showed reaction mostly complete. The mixture was diluted with Ethyl Acetate and quenched with saturated NaHCO3. The organic phase was then washed with brine, dried over Na2SO4, filtered and evaporated in vacuo. Purification by silica gel chromatography (2% MeOH/CH2Cl2) followed by formation of the HCl salt using 1N HCl in ether provided the title compound (0.166 g, 35%). MS: APCI: M+1: 489.2 (Exact Mass: 488.21).

Workup

  1. customreaction mostly complete
  2. customquenched with saturated NaHCO3
  3. washThe organic phase was then washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customPurification by silica gel chromatography (2% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-b201846427c347308ae82dd464ff81bd
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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