Acetone → HCID 23643984, compound

HRID 2242005Notes

Reaction equation

HRID 2242005 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]2)=[C:8]2[C:3]=1[C:4]([O:23][CH3:24])=[CH:5][C:6]([C:19]([F:22])([F:21])[F:20])=[N:7]2.[CH3:25][O:26][C:27]1[CH:28]=[C:29]2[C:34](=[C:35]([N:37]3[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)[CH:36]=1)[N:33]=[CH:32][CH:31]=[CH:30]2.C([BH3-])#N.[Na+].CC(C)=O.[Cl-:51].[Na+].O>CO.CCCCCC>[ClH:51].[ClH:51].[ClH:51].[F:1][C:2]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:13][CH2:14][CH:15]([N:40]3[CH2:41][CH2:42][N:37]([C:35]4[CH:36]=[C:27]([O:26][CH3:25])[CH:28]=[C:29]5[C:34]=4[N:33]=[CH:32][CH:31]=[CH:30]5)[CH2:38][CH2:39]3)[CH2:16][CH2:17]2)=[C:8]2[C:3]=1[C:4]([O:23][CH3:24])=[CH:5][C:6]([C:19]([F:21])([F:20])[F:22])=[N:7]2

Participants

8

Reactant 5

HCID 180Acetone2×HCID 5003444Sodium cyanoborohydride2×HCID 184141776-Methoxy-8-(piperazin-1-YL)quinolineHCID 25111871HCID 25111871, compoundHCID 57417360Sodium chloride; water

Product 1

HCID 23643984HCID 23643984, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8058HexaneSolvent2×

Procedure

To a solution of 1-[5-fluoro-4-methoxy-2-(trifluoromethyl)quinolin-8-yl]piperidin-4-one (Step 4, 0.31 g, 0.9 mmol, 1 eq.) and 6-methoxy-8-(1-piperazinyl)quinoline (Example A, Step 4, 0.30 g, 1.23 mmol, 1.37 eq.) in anhydrous methanol (20 mL) was added sodium cyanoborohydride (0.103 g, 1.64 mmol, 1.82 eq.). The resulting mixture was stirred overnight at room temperature under nitrogen (app. 18 hr). An additional aliquot of sodium cyanoborohydride (0.10 g, 1.59 mmol, 1.76 eq.) was added and stirring at room temperature was continued overnight. The resulting reaction mixture was poured into brine and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated on a rotary evaporator to a yellow oil. The desired product was isolated by chromatography on a 40 g silica column (1000 mL 20% acetone in hexane followed by 500 mL 30% acetone in hexane) as a yellow solid (0.113 g, 22% yield). The free base was converted to its trihydrochloride sesquihydrate salt by dissolving it in dichloromethane (3 mL), adding diethyl ether (9 mL), cooling in an ice bath and adding 1M HCl/Et2O (1 mL). The resulting yellow solid was collected by vacuum filtration, washed with ether and dried in vacuo to give 0.152 g. MS (ES) m/z (relative intensity): 570 (M+H)+ (100).

Workup

  1. stirringstirring at room temperature
  2. waitwas continued overnight
  3. customThe resulting reaction mixture
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated on a rotary evaporator to a yellow oil

Sources & evidence

ORD record
ord-8dd0ca8f350547f882a65ec27197551c
Source dataset
uspto-grants-2010_03
Patent number
US07671056B2

Reaction notes

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