Triethylamine → HCID 178441819, compound

HRID 705121

Reaction equation

HRID 705121 reaction equation
[CH2:1]([C:5]1[N:6]=[C:7]([NH:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH3:32])[CH:24]=2)[C:8]2[NH:13][N:12]=[C:11]([C:14]#[C:15][CH2:16][CH2:17][CH2:18][CH2:19]Cl)[C:9]=2[N:10]=1)[CH2:2][CH2:3][CH3:4].[CH2:33]([N:35](CC)[CH2:36][CH3:37])[CH3:34].N1CCCC1>C(#N)C>[CH2:1]([C:5]1[N:6]=[C:7]([NH:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH3:32])[CH:24]=2)[C:8]2[NH:13][N:12]=[C:11]([C:14]#[C:15][CH2:16][CH2:17][CH2:18][CH2:19][N:35]3[CH2:36][CH2:37][CH2:34][CH2:33]3)[C:9]=2[N:10]=1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 31268Pyrrolidine2×HCID 178441818HCID 178441818, compound

Product 1

HCID 178441819HCID 178441819, compoundYield 117.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 5-butyl-3-(6-chlorohex-1-yn-1-yl)-N-(3,4-dimethoxybenzyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine (3.334 g, 7.31 mmol) in anhydrous acetonitrile (4 mL) was added triethylamine (3.06 mL, 21.94 mmol) and pyrrolidine (1.831 mL, 21.94 mmol). The solution was stirred at 70° C. for 18 hours. A further equivalent of pyrrolidine (0.61 mL, 7.31 mmol) and triethylamine (1.019 mL, 7.31 mmol) were added to the reaction mixture. The solution was stirred at 70° C. for a further 3 hours. The cooled reaction mixture was evaporated in-vacuo and the residue partitioned between ethyl acetate and water/brine (1:1). The organic phase was separated, passed through a hydrophobic frit and evaporated in-vacuo to yield a sticky brown gum (4.226 g). The gum was dissolved in the minimum volume of dichloromethane, loaded onto a 340 g silica pre-conditioned cartridge and purified by chromatography using dichloromethane over 1 column volume followed by 0-30% methanol (+1% triethylamine) in dichloromethane gradient over 14 column volumes followed by 30% methanol (+1% triethylamine) in dichloromethane over 3 column volumes. Appropriate fractions were combined and evaporated in-vacuo to yield the title compound as a sticky brown gum (1.838 g).

Workup

  1. stirringThe solution was stirred at 70° C. for a further 3 hours
  2. customThe cooled reaction mixture
  3. customwas evaporated in-vacuo
  4. customthe residue partitioned between ethyl acetate and water/brine (1:1)
  5. customThe organic phase was separated
  6. customevaporated in-vacuo

Sources & evidence

ORD record
ord-5557e82b61c8464584c6c01e1c275024
Source dataset
uspto-grants-2015_11
Patent number
US09173872B2

Linked notes

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