Piperidine → HCID 178441458, compound

HRID 705123Notes

Reaction equation

HRID 705123 reaction equation
[CH2:1]([C:5]1[NH:6][C:7](=[O:20])[C:8]2[NH:13][N:12]=[C:11]([C:14]#[C:15][CH2:16][CH2:17][CH2:18]Cl)[C:9]=2[N:10]=1)[CH2:2][CH2:3][CH3:4].[NH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.C(N(CC)CC)C.[H][H]>CN(C)C=O.C(O)C.[Pd].CO.CS(C)=O>[CH2:1]([C:5]1[NH:6][C:7](=[O:20])[C:8]2[NH:13][N:12]=[C:11]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)[C:9]=2[N:10]=1)[CH2:2][CH2:3][CH3:4]

Participants

9

Reactant 4

HCID 8082Piperidine3×HCID 8471Triethylamine3×HCID 178418361HCID 178418361, compound2×HCID 178441457HCID 178441457, compound

Product 1

HCID 178441458HCID 178441458, compoundYield 45.9%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalyst2×HCID 702EthanolSolventHCID 6228DimethylformamideSolvent2×HCID 22036561Dimethyl sulfoxide methanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-butyl-3-(5-chloropent-1-yn-1-yl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one (168 mg, 0.574 mmol) in anhydrous N,N-dimethylformamide (3.5 mL) was added a solution of piperidine (147 mg, 1.722 mmol) in anhydrous N,N-dimethylformamide (0.5 mL) and triethylamine (0.32 mL, 2.295 mmol). The reaction was stirred at 80° C. for 190 minutes. A further 73 mg (0.857 mmol) of piperidine and 160 μL (1.148 mmol) of triethylamine was added to the reaction. The reaction was stirred at 80° C. for a further 2.5 hours and then at room temperature for 15.5 hours. A further 73 mg (0.857 mmol) of piperidine and 160 μL (1.148 mmol) of triethylamine was added to the reaction. The reaction was stirred at 80° C. for 2.5 hours. The reaction was evaporated in-vacuo to yield a dark yellow oil. A solution of the oil in ethanol (50 mL) was passed through the H-cube (settings: 30° C., full hydrogen, 1 mL/min flow rate and 10% palladium on carbon CatCart30 as the catalyst). A new 10% palladium on carbon CatCart30 cartridge was inserted into the H-cube and the solution was passed through the H-cube again (settings: 30° C., full hydrogen, 1 mL/min flow rate). The solution was evaporated in-vacuo to yield a pale yellow oil. The oil was dissolved in MeOH:DMSO (1:1) (3×1 mL) and purified by MDAP (Method B). Appropriate fractions were combined and evaporated in-vacuo to yield the title compound as a pale yellow solid (91 mg).

Workup

  1. stirringThe reaction was stirred at 80° C. for a further 2.5 hours
  2. waitat room temperature for 15.5 hours
  3. stirringThe reaction was stirred at 80° C. for 2.5 hours
  4. customThe reaction was evaporated in-vacuo
  5. customto yield a dark yellow oil
  6. customThe solution was evaporated in-vacuo
  7. customto yield a pale yellow oil
  8. custompurified by MDAP (Method B)
  9. customevaporated in-vacuo

Sources & evidence

ORD record
ord-a0db29a0ebf5437cb62d9e7086946fc2
Source dataset
uspto-grants-2015_11
Patent number
US09173872B2

Reaction notes

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