3-Cyclobutyl-1-iodoimidazo[1,5-a]pyrazin-8-amine → 3-Cyclobutyl-1-[1-(2-trimethylsilylethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]imidazo[1,5-a]pyrazin-8-amine

HRID 1878876Notes

Reaction equation

HRID 1878876 reaction equation
[CH3:1][Si:2]([CH3:30])([CH3:29])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:11]2=[N:12][CH:13]=[CH:14][CH:15]=[C:10]2[CH:9]=[C:8]1[Sn](CCCC)(CCCC)CCCC.[CH:31]1([C:35]2[N:39]3[CH:40]=[CH:41][N:42]=[C:43]([NH2:44])[C:38]3=[C:37](I)[N:36]=2)[CH2:34][CH2:33][CH2:32]1>C(O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:31]1([C:35]2[N:39]3[CH:40]=[CH:41][N:42]=[C:43]([NH2:44])[C:38]3=[C:37]([C:8]3[N:7]([CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:1])([CH3:29])[CH3:30])[C:11]4=[N:12][CH:13]=[CH:14][CH:15]=[C:10]4[CH:9]=3)[N:36]=2)[CH2:32][CH2:33][CH2:34]1

Participants

5

Reactant 2

HCID 426093653-Cyclobutyl-1-iodoimidazo[1,5-a]pyrazin-8-amineHCID 59133036N-(2-Trimethylsilyl-1-ethoxymethyl)-2-(tributylstannyl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 591330243-Cyclobutyl-1-[1-(2-trimethylsilylethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]imidazo[1,5-a]pyrazin-8-amineYield 24.9%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolvent

Procedure

A mixture of N-(2-trimethylsilyl-1-ethoxymethyl)-2-(tributylstannyl)-1H-pyrrolo[2,3-b]pyridine (110 mg, 0.20 mmol), 3-cyclobutyl-1-iodoimidazo[1,5-α]pyrazin-8-amine (50 mg, 0.1592 mmol) and bis(triphenylphosphine)palladium(II) chloride (10 mg, 0.02 mmol) in ethanol (2 mL) was heated at reflux for 48 h. The mixture was then cooled to rt, filtered through a pad of Celite and concentrated in vacuo. The residue thus obtained was chromatographed over silica gel eluting with hex:EtOAc to afford 17.2 mg of the title compound. 1H NMR (400 MHz CDCl3) δ 0.22 (s, 9H), 0.70 (t, 2H), 1.87-2.19 (m, 2H), 2.49-2.64 (m, 4H), 3.37 (t, 2H), 3.81-3.86 (m, 1H), 5.51 (bs, 2H), 6.07 (s, 2H), 6.67 (s, 1H), 7.10-7.16 (m, 3H), 7.93 (dd, J=1.6, 8.0 Hz, 1H) and 8.41 (dd, J=1.6, 4.8 Hz, 1H). MS (ES+): m/z: 435.21 [MH+].

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 48 h
  3. filtrationfiltered through a pad of Celite
  4. concentrationconcentrated in vacuo
  5. customThe residue thus obtained
  6. customwas chromatographed over silica gel eluting with hex

Sources & evidence

ORD record
ord-a7863b3ec98e4654a1283b443e9ae7b0
Source dataset
uspto-grants-2012_11
Patent number
US08314111B2

Reaction notes

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