Triethylamine → HCID 178441456, compound

HRID 705118Notes

Reaction equation

HRID 705118 reaction equation
[CH2:1]([C:5]1[NH:6][C:7](=[O:15])[C:8]2[NH:13][N:12]=[C:11](I)[C:9]=2[N:10]=1)[CH2:2][CH2:3][CH3:4].[Cl:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]#[CH:22].C(N(CC)CC)C>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[CH2:1]([C:5]1[NH:6][C:7](=[O:15])[C:8]2[NH:13][N:12]=[C:11]([C:22]#[C:21][CH2:20][CH2:19][CH2:18][CH2:17][Cl:16])[C:9]=2[N:10]=1)[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 2720016-Chloro-1-hexyneHCID 178441541HCID 178441541, compound

Product 1

HCID 178441456HCID 178441456, compoundYield 166.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of 5-butyl-3-iodo-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one (4.97 g, 15.62 mmol) in N,N-dimethylformamide (100 mL) was added bis(triphenylphosphine)palladium(II)dichloride (1.228 g, 1.750 mmol) and copper(I) iodide (0.595 g, 3.12 mmol). The solution was stirred and degassed with nitrogen for 5 minutes then the reaction mixture placed under a nitrogen atmosphere. A solution of 6-chloro-1-hexyne (3.64 g, 31.2 mmol) and triethylamine (4.36 mL, 31.2 mmol) in N,N-dimethylformamide (30 mL) was added dropwise over 10 minutes. The reaction mixture was stirred at ambient temperature for a further 10 minutes then heated to 60° C. for 2.5 hours. The reaction mixture was concentrated in vacuo at 60° C. and the resulting residue partitioned between ethyl acetate (250 mL) and a 1:1 mixture of water:brine (500 mL). The organic layer was separated and the aqueous layer back extracted with ethyl acetate (250 mL). The combined organic phases were dried through a hydrophobic frit and concentrated in vacuo to give a brown solid (8.0 g). The residue was dissolved in a 1:1 mixture of MeOH:DCM and absorbed onto Florisil. The solid was loaded and purified by chromatography on silica (330 g) using a 0-100% ethyl acetate-cyclohexane gradient over 10 column volumes followed by flushing with ethyl acetate for 9 column volumes. The appropriate fractions were combined and evaporated in vacuo to give a yellow solid (3.55 g). The solid was triturated with diisopropyl ether, filtered and dried in vacuo at 50° C. to give the title compound as a pale yellow solid (3.14 g).

Workup

  1. customdegassed with nitrogen for 5 minutes
  2. stirringThe reaction mixture was stirred at ambient temperature for a further 10 minutes
  3. concentrationThe reaction mixture was concentrated in vacuo at 60° C.
  4. customthe resulting residue partitioned between ethyl acetate (250 mL)
  5. additiona 1:1 mixture of water
  6. customThe organic layer was separated
  7. extractionthe aqueous layer back extracted with ethyl acetate (250 mL)
  8. customThe combined organic phases were dried through a hydrophobic frit
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ad1481b6ec6f40c387a05a058761283b
Source dataset
uspto-grants-2015_11
Patent number
US09173872B2

Reaction notes

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