1-Butanol → 6-Butoxy-1-(4-chlorobenzyl)-4-[4-(4-fluorophenyl)piperazin-1-yl]-1,3,5-triazin-2(1H)-one

HRID 1477696Notes

Reaction equation

HRID 1477696 reaction equation
Cl[C:2]1[NH:7][C:6](=[O:8])[N:5]=[C:4]([N:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)[N:3]=1.[H-].[Li+].[Cl:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29]Br)=[CH:27][CH:26]=1.[CH2:33]([OH:37])[CH2:34][CH2:35][CH3:36]>C(OCC)(=O)C.O.COCCOC.CN(C)C=O>[CH2:33]([O:37][C:2]1[N:7]([CH2:29][C:28]2[CH:31]=[CH:32][C:25]([Cl:24])=[CH:26][CH:27]=2)[C:6](=[O:8])[N:5]=[C:4]([N:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)[N:3]=1)[CH2:34][CH2:35][CH3:36]

Participants

9

Reactant 4

HCID 2631-ButanolHCID 62714Lithium hydride2×HCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 1369330476-Chloro-4-[4-(4-fluorophenyl)piperazin-1-yl]-1,3,5-triazin-2(1H)-one

Product 1

HCID 1178398256-Butoxy-1-(4-chlorobenzyl)-4-[4-(4-fluorophenyl)piperazin-1-yl]-1,3,5-triazin-2(1H)-oneYield 23.8%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-chloro-4-[4-(4-fluorophenyl)piperazin-1-yl]-1,3,5-triazin-2(1H)-one (50 mg, 0.16 mmol) synthesized in Reference Synthesis Example 2 in a solvent mixture of N,N-dimethylformamide (1 mL) and 1,2-dimethoxyethane (1 mL), lithium hydride (1.3 mg, 0.16 mmol) was added at 0° C. and the resultant mixture was stirred at room temperature for 15 minutes. To the mixture, 4-chlorobenzyl bromide (40 mg, 0.19 mmol) was added and the resultant mixture was stirred at room temperature for 30 minutes and then at 60° C. for 2 hours. Next, at room temperature, 1-butanol (30 μL, 0.32 mmol) and lithium hydride (2.6 mg, 0.32 mmol) were added to the resultant mixture and the resultant mixture was stirred for 30 hours. After the completion of the reaction, water was added to the reaction solution and extraction with ethyl acetate from the resultant reaction solution was performed three times. The organic layer was washed with brine, was dried over anhydrous sodium sulfate, and was concentrated under reduced pressure. The resultant residue was purified by amino-type thin-layer chromatography (hexane/ethyl acetate=1/1 (v/v)) to obtain the title compound (18 mg, yield: 21%).

Workup

  1. additionwas added at 0° C.
  2. customreaction solution
  3. washThe organic layer was washed with brine
  4. dry with materialwas dried over anhydrous sodium sulfate
  5. concentrationwas concentrated under reduced pressure
  6. customThe resultant residue was purified by amino-type thin-layer chromatography (hexane/ethyl acetate=1/1 (v/v))

Sources & evidence

ORD record
ord-d5e1a16caf974de7a5ec8438eac79b44
Source dataset
uspto-grants-2016_08
Patent number
US09403798B2

Reaction notes

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