Methanol → HCID 66737912, compound

HRID 550182Notes

Reaction equation

HRID 550182 reaction equation
[CH:1]1([C:5]2[N:9]3[CH:10]=[CH:11][N:12]=C(N)[C:8]3=[C:7](I)[N:6]=2)[CH2:4][CH2:3][CH2:2]1.[CH3:16][OH:17].C(N(CC)C(C)C)(C)C.[C:27](#[N:29])[CH3:28].[OH2:30]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:29][C:27]1[C:28]2[N:9]([C:5]([CH:1]3[CH2:4][CH2:3][CH2:2]3)=[N:6][C:7]=2[C:8]([O:17][CH3:16])=[O:30])[CH:10]=[CH:11][N:12]=1

Participants

7

Reactant 5

HCID 887MethanolHCID 962WaterHCID 6342AcetonitrileHCID 81531DiisopropylethylamineHCID 426093653-Cyclobutyl-1-iodoimidazo[1,5-a]pyrazin-8-amine

Product 1

HCID 66737912HCID 66737912, compound

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
70 °C

Procedure

3-Cyclobutyl-1-iodoimidazo[1,5-a]pyrazin-8-amine (500 mg, 2 mmol) and tetrakis(triphenylphosphine)palladium(0) (100 mg, 0.1 mmol) was degassed dry three times then treated with methanol (20 mL) and N,N-diisopropylethylamine (0.7 mL, 4.0 mmol) and the mixture heated at 70° C. under an atmosphere of carbon monoxide, with intermittent bubbling of this gas under the surface of the reaction mixture. After 3 d heating with extensive bubbling through of the solution with carbon monoxide and some addition of fresh catalyst after day 2, TLC (10% MeOH/DCM) indicated the reaction to be complete. The reaction mixture was diluted with water, extracted with DCM and the extracts washed with water and brine, then dried over magnesium sulphate, and concentrated in vacuo to afford an orange solid which was rectystallised from acetonitrile to afford methyl 8-amino-3-cyclobutylimidazo[1,5-a]pyrazine-1-carboxylate. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.97-2.06 (m, 1 H), 2.10-2.26 (m, 1 H), 2.43-2.54 (m, 2 H), 2.53-2.68 (m, 2 H), 3.78 (dd, J=9.09, 8.08 Hz, 1 H), 4.01 (s, 3 H), 7.08 (d, J=4.80 Hz, 1 H), 7.22 (d, J=4.80 Hz, 1 H), 7.38 (br. s., 1 H), 7.69 (br. s., 1 H).

Workup

  1. customdry three times
  2. customwith intermittent bubbling of this gas under the surface of the reaction mixture
  3. temperatureAfter 3 d heating
  4. customwith extensive bubbling through of the solution with carbon monoxide
  5. additionsome addition of fresh catalyst after day 2, TLC (10% MeOH/DCM)
  6. customthe reaction
  7. extractionextracted with DCM
  8. washthe extracts washed with water and brine
  9. dry with materialdried over magnesium sulphate
  10. concentrationconcentrated in vacuo
  11. customto afford an orange solid which

Sources & evidence

ORD record
ord-adaecd0e3b30486f9789835a0c4eb0ff
Source dataset
uspto-grants-2011_05
Patent number
US07943767B2

Reaction notes

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