Sodium cyanoborohydride → 7-Fluoro-8-{4-[4-(6-methoxyquinolin-8-yl)piperazin-1-yl]piperidin-1-yl}Quinoline

HRID 2241983Notes

Reaction equation

HRID 2241983 reaction equation
[F:1][C:2]1[C:11]([N:12]2[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]2)=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.[CH3:19][O:20][C:21]1[CH:22]=[C:23]2[C:28](=[C:29]([N:31]3[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]3)[CH:30]=1)[N:27]=[CH:26][CH:25]=[CH:24]2.C([BH3-])#N.[Na+]>CO.[Cl-].[Na+].O>[F:1][C:2]1[C:11]([N:12]2[CH2:17][CH2:16][CH:15]([N:34]3[CH2:35][CH2:36][N:31]([C:29]4[CH:30]=[C:21]([O:20][CH3:19])[CH:22]=[C:23]5[C:28]=4[N:27]=[CH:26][CH:25]=[CH:24]5)[CH2:32][CH2:33]3)[CH2:14][CH2:13]2)=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 5003444Sodium cyanoborohydride2×HCID 184141776-Methoxy-8-(piperazin-1-YL)quinolineHCID 573365271-(7-Fluoroquinolin-8-YL)piperidin-4-one

Product 1

HCID 120041147-Fluoro-8-{4-[4-(6-methoxyquinolin-8-yl)piperazin-1-yl]piperidin-1-yl}Quinoline

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 1-(7-fluoroquinolin-8-yl)piperidin-4-one (Step 3, 0.26 g) and 6-methyoxy-8-(1-piperazinyl)quinoline (Example A, Step 4; 0.26 g) in anhydrous methanol (10 mL) was added sodium cyanoborohydride (0.11 g). The resulting mixture was stirred at room temperature under nitrogen for 18 hours. An additional aliquot of sodium cyanoborohydride (0.11 g) was added and stirring at room temperature was continued for another 24 hours. The resulting reaction mixture was poured into brine and extracted with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated on a rotary evaporator. The crude product was purified by flash chromatography on silica gel using hexane/acetone to give the desired product, which was converted to its trihydrochloride salt in CH2Cl2 using 1M HCl/Et2O to provide 0.12 g of a yellow solid; MS (ES) m/z (relative intensity): 472 (M+H)+ (100).

Workup

  1. stirringstirring at room temperature
  2. waitwas continued for another 24 hours
  3. customThe resulting reaction mixture
  4. extractionextracted with ethyl acetate
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated on a rotary evaporator
  8. customThe crude product was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-69bde18468104ad09e7d5d25dffb312d
Source dataset
uspto-grants-2010_03
Patent number
US07671056B2

Reaction notes

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