Methanol → HCID 66737912, compound

HRID 1993260Notes

Reaction equation

HRID 1993260 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.[CH3:16][OH:17].[CH:18](N(CC)C(C)C)(C)C.[OH2:27]>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>[NH2:14][C:13]1[C:8]2[N:9]([C:5]([CH:1]3[CH2:4][CH2:3][CH2:2]3)=[N:6][C:7]=2[C:16]([O:27][CH3:18])=[O:17])[CH:10]=[CH:11][N:12]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 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 3d 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 recrystallised 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., 1H), 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 3d 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
  12. customwas recrystallised from acetonitrile

Sources & evidence

ORD record
ord-6d6ec24cce5a4c28b3b1eae8bdf27ed8
Source dataset
uspto-grants-2010_01
Patent number
US07651687B2

Reaction notes

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