Ammonia → 3-tert-Butyl-1-(2-phenylquinolin-7-yl)-imidazo[1,5-a]pyrazin-8-ylamine

HRID 244096Notes

Reaction equation

HRID 244096 reaction equation
[NH3:1].[C:2]([C:6]1[N:10]2[CH:11]=[CH:12][N:13]=[C:14](Cl)[C:9]2=[C:8]([C:16]2[CH:25]=[C:24]3[C:19]([CH:20]=[CH:21][C:22]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[N:23]3)=[CH:18][CH:17]=2)[N:7]=1)([CH3:5])([CH3:4])[CH3:3]>N.CC(O)C>[C:2]([C:6]1[N:10]2[CH:11]=[CH:12][N:13]=[C:14]([NH2:1])[C:9]2=[C:8]([C:16]2[CH:25]=[C:24]3[C:19]([CH:20]=[CH:21][C:22]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[N:23]3)=[CH:18][CH:17]=2)[N:7]=1)([CH3:5])([CH3:4])[CH3:3]

Participants

4

Reactant 2

HCID 222AmmoniaHCID 536290227-(3-Tert-butyl-8-chloroimidazo[1,5-a]pyrazin-1-yl)-2-phenylquinoline

Product 1

HCID 115240333-tert-Butyl-1-(2-phenylquinolin-7-yl)-imidazo[1,5-a]pyrazin-8-ylamine

Reagents, catalysts & solvents 1

HCID 183319422-Propanol, reaction products with ammonia, distn. residuesSolvent

Conditions

Temperature
110 °C

Procedure

Gaseous NH3 was condensed into a cooled (−78° C.) solution of 7-(3-tert-butyl-8-chloroimidazo[1,5-a]pyrazin-1-yl)-2-phenylquinoline (92.5 mg, 0.224 mmol) in NH3/i-PrOH (2M, 5 mL) in a pressure tube until the volume had doubled. The tube was sealed and heated to 110° C. for 21 h. After excess NH3 and i-PrOH were removed in vacuo, the residue was suspended between CH2Cl2 and water, the layers were separated, and the aqueous layer was extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with brine (3×25 mL), dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified by chromatography on silica gel [Jones Flashmaster, 5 g/25 mL cartridge, eluting with MeOH (7N NH3):CH2Cl2 1%→+2%], affording the title compound, as a fine yellow solid. 1H NMR (CDCl3, 400 MHz) δ 1.25 (s, 9H), 5.18 (s, —NH2), 7.08 (d, J=4.8 Hz, 1H), 7.45-7.51 (m, 1H), 7.51-7.57 (m, 3H), 7.90-7.97 (m, 3H), 8.17-8.22 (m, 2H), 8.27 (d, J=8.4 Hz, 1H), 8.42-8.44 (m, 1H); MS (ES+): m/z 394.1 (25) [MH+]; HPLC: tR=2.5 min (OpenLynx, polar 5 min).

Workup

  1. customcondensed into
  2. customThe tube was sealed
  3. customAfter excess NH3 and i-PrOH were removed in vacuo
  4. customthe layers were separated
  5. extractionthe aqueous layer was extracted with CH2Cl2 (3×15 mL)
  6. washThe combined organic layers were washed with brine (3×25 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude material was purified by chromatography on silica gel [Jones Flashmaster, 5 g/25 mL cartridge, eluting with MeOH (7N NH3):CH2Cl2 1%→+2%]

Sources & evidence

ORD record
ord-384ea2834fdb4d18adc1c5795170f726
Source dataset
uspto-grants-2014_02
Patent number
US08653268B2

Reaction notes

Loading…