Nitrogen → HCID 16662430, compound

HRID 1442568Notes

Reaction equation

HRID 1442568 reaction equation
[CH:1]1([C:5]2[N:9]3[CH:10]=[CH:11][N:12]=[C:13]([NH2:14])[C:8]3=[C:7](I)[N:6]=2)[CH2:4][CH2:3][CH2:2]1.N#N.C(N(CC)CC)C.[C:25]1([C:31]#[CH:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN(C)C=O.[Cu]I>[CH:1]1([C:5]2[N:9]3[CH:10]=[CH:11][N:12]=[C:13]([NH2:14])[C:8]3=[C:7]([C:32]#[C:31][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:6]=2)[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 947NitrogenHCID 8471TriethylamineHCID 10821PhenylacetyleneHCID 426093653-Cyclobutyl-1-iodoimidazo[1,5-a]pyrazin-8-amine

Product 1

HCID 16662430HCID 16662430, compoundYield 28.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 3-cyclobutyl-1-iodoimidazo[1,5-a]pyrazin-8-amine (50 mg, 0.159 mmol) in N,N-dimethylformamide (6 mL) and evacuated and charged with N2 three times, then treated with triethylamine (0.044 mL, 0.318 mmol), phenylacetylene (0.175 mL, 1.59 mmol), and copper (I) iodide (3.0 mg, 0.0159 mmol). The mixture re-evacuated and charged with N2 twice more, then charged with tetrakis(triphenylphoshine)palladium (0) (20.2 mg, 0.0175 mmol) and evacuated and charged with N2 a final two times. The reaction mixture was stirred at rt for 16 h, then concentrated in vacuo, dissolved in MeOH/CH3CN (1:1)(4 mL) and was filtered through a 0.45 fritted μM autovial prior to purification via mass directed preparative HPLC that afforded 13 mg of the title compound. 1H NMR (DMSO-d6, 400 MHz) δ 1.87-1.99 (m, 1H), 2.01-2.15 (m, 1H), 2.32-2.47 (m, 4H), 3.87-3.99 (m, 1H), 6.66 (brs, 2H), 7.08 (brs, 1H), 7.40-7.51 (m, 4H), 7.59-7.67 (m, 2H); MS (ES+): m/z 289.13 [MH+].

Workup

  1. customThe mixture re-evacuated
  2. additioncharged with N2 twice more
  3. customevacuated
  4. additioncharged with N2 a final two times
  5. concentrationconcentrated in vacuo
  6. dissolutiondissolved in MeOH/CH3CN (1:1)(4 mL)
  7. filtrationwas filtered through a 0.45 fritted μM autovial
  8. customto purification via mass

Sources & evidence

ORD record
ord-1707d8371e594c37927391677b2a61c9
Source dataset
uspto-grants-2010_02
Patent number
US07659274B2

Reaction notes

Loading…