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

HRID 2241985

Reaction equation

HRID 2241985 reaction equation
[F:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]2)=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[F:19][C:20]1[CH:21]=[C:22]2[C:27](=[C:28]([N:30]3[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]3)[CH:29]=1)[N:26]=[CH:25][CH:24]=[CH:23]2.C([BH3-])#N.[Na+].CCCCCC.CC(C)=O>CO.[Cl-].[Na+].O>[F:19][C:20]1[CH:21]=[C:22]2[C:27](=[C:28]([N:30]3[CH2:35][CH2:34][N:33]([CH:15]4[CH2:16][CH2:17][N:12]([C:3]5[C:2]([F:1])=[C:11]6[C:6]([CH:7]=[CH:8][CH:9]=[N:10]6)=[CH:5][CH:4]=5)[CH2:13][CH2:14]4)[CH2:32][CH2:31]3)[CH:29]=1)[N:26]=[CH:25][CH:24]=[CH:23]2

Participants

7

Reactant 4

HCID 5003444Sodium cyanoborohydride2×HCID 21880519Acetone hexaneHCID 589754886-Fluoro-8-(piperazin-1-yl)quinolineHCID 592048601-(8-Fluoroquinolin-7-yl)piperidin-4-one

Product 1

HCID 120041156-Fluoro-8-{4-[1-(8-fluoroquinolin-7-yl)piperidin-4-yl]piperazin-1-yl}quinoline

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 1-(8-fluoroquinolin-7-yl)piperidin-4-one (Step 1, 0.25 g) and 6-fluoro-8-(1-piperazinyl)quinoline (Example B, Step 3; 0.25 g) in anhydrous methanol (10 mL) was added sodium cyanoborohydride (0.11 g). The resulting mixture was stirred at room temperature for 18 hours. An additional aliquot of sodium cyanoborohydride (0.10 g) was added and stirring at room temperature was continued for another 24 hours. The 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 isolated by flash chromatography on silica gel using hexane/acetone to give the desired product as a off-white solid, which was converted to its trihydrochloride salt in CH2Cl2/Et2O diethyl ether using 1M HCl/Et2O to provide 0.11 g as a yellow solid; MS (ES) m/z (relative intensity): 460 (M+H)+ (100).

Workup

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

Sources & evidence

ORD record
ord-bd6781dca4b646cf90acd8b5b5392cae
Source dataset
uspto-grants-2010_03
Patent number
US07671056B2

Linked notes

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