3-Cyclobutyl-1-quinolin-7-ylimidazo[1,5-a]pyrazin-8-ylamine → 3-Cyclobutyl-1-(2-thiophen-2-yl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-8-ylamine

HRID 244099

Reaction equation

HRID 244099 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]([C:15]3[CH:24]=[C:23]4[C:18]([CH:19]=[CH:20][CH:21]=[N:22]4)=[CH:17][CH:16]=3)[N:6]=2)[CH2:4][CH2:3][CH2:2]1.[S:25]1[CH:29]=[CH:28][CH:27]=[C:26]1[Li]>C1COCC1>[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:15]3[CH:24]=[C:23]4[C:18]([CH:19]=[CH:20][C:21]([C:26]5[S:25][CH:29]=[CH:28][CH:27]=5)=[N:22]4)=[CH:17][CH:16]=3)[N:6]=2)[CH2:2][CH2:3][CH2:4]1

Participants

4

Reactant 2

HCID 444513373-Cyclobutyl-1-quinolin-7-ylimidazo[1,5-a]pyrazin-8-ylamineHCID 178418439HCID 178418439, compound2×

Product 1

HCID 115095063-Cyclobutyl-1-(2-thiophen-2-yl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-8-ylamine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled (ice/water) solution of 3-cyclobutyl-1-quinolin-7-ylimidazo[1,5-a]pyrazin-8-ylamine (52.7 mg, 0.167 mmol) in THF (5 mL) was added 2-thienyllithium (1 M in THF; 0.6 mL, 0.6 mmol), then the cooling bath was removed, and the solution was stirred overnight at ambient temperature. After 1 d and 2 d, more 2-thienyllithium (0.2 mL, 0.2 mmol) was added, and stirring was continued. The reaction was quenched by adding water and sat. NH4Cl solution, the mixture was extracted with CH2Cl2 (3×20 mL), and the combined organic extracts were washed with brine and dried over MgSO4. Air was bubbled into the solution for 8 h. The crude material was adsorbed onto Hydromatrix and chromatographed on silica gel [Jones Flashmaster, 5 g/25 mL cartridge, eluting with CH2Cl2 (1-6)→1% MeOH in CH2Cl2 (7-21)→2% MeOH in CH2Cl2 (22-43)], yielding a yellow film. Further purification by preparative TLC (20×20 cm silica gel plates, 500 μM thickness, eluting with 3% MeOH in CH2Cl2 four times) yielded the title compound as a yellow solid;

Workup

  1. customthe cooling bath was removed
  2. waitAfter 1 d
  3. stirringstirring
  4. customThe reaction was quenched
  5. additionby adding water and sat. NH4Cl solution
  6. extractionthe mixture was extracted with CH2Cl2 (3×20 mL)
  7. washthe combined organic extracts were washed with brine
  8. dry with materialdried over MgSO4
  9. customAir was bubbled into the solution for 8 h
  10. customchromatographed on silica gel [Jones Flashmaster, 5 g/25 mL cartridge, eluting with CH2Cl2 (1-6)→1% MeOH in CH2Cl2 (7-21)→2% MeOH in CH2Cl2 (22-43)]
  11. customyielding a yellow film
  12. customFurther purification
  13. washby preparative TLC (20×20 cm silica gel plates, 500 μM thickness, eluting with 3% MeOH in CH2Cl2 four times)

Sources & evidence

ORD record
ord-814751cc6867418db849dba893d882ce
Source dataset
uspto-grants-2014_02
Patent number
US08653268B2

Linked notes

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