Ammonia → HCID 11293122, compound

HRID 2373893Notes

Reaction equation

HRID 2373893 reaction equation
[NH3:1].[CH2:2]([O:9][C:10]1[CH:11]=[C:12]([C:16]2[N:17]=[C:18]([C:26]3[CH:27]=[C:28]([CH2:32][OH:33])[CH:29]=[CH:30][CH:31]=3)[N:19]3[CH:24]=[CH:23][N:22]=[C:21](Cl)[C:20]=23)[CH:13]=[CH:14][CH:15]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1>N.CC(O)C>[NH2:1][C:21]1[C:20]2[N:19]([C:18]([C:26]3[CH:27]=[C:28]([CH2:32][OH:33])[CH:29]=[CH:30][CH:31]=3)=[N:17][C:16]=2[C:12]2[CH:13]=[CH:14][CH:15]=[C:10]([O:9][CH2:2][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)[CH:11]=2)[CH:24]=[CH:23][N:22]=1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 59852782HCID 59852782, compound

Product 1

HCID 11293122HCID 11293122, compoundYield 89%

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 {3-[1-(3-benzyloxyphenyl)-8-chloroimidazo[1,5-a]pyrazin-3-yl]-phenyl}-methanol (366 mg, 0.829 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 19 h. After excess NH3/i-PrOH was removed in vacuo, the residue was suspended between CH2Cl2 and water, the layers were separated, and the aqueous layer was extracted with CH2Cl2 (3×30 mL). The combined organic layers were washed with brine (3×30 mL), dried over anhydrous MgSO4, and filtered. The crude material was purified by filtration through a plug of silica gel, eluting with 5% MeOH:CH2Cl2 (400 mL), concentrated in vacuo, giving 311.5 mg (89%, 0.737 mmol) of the title compound, as a yellow solid; 1H NMR (CDCl3, 400 MHz) δ 4.80 (s, 2H), 5.09 (s, —NH2), 5.16 (s, 2H), 7.05-7.09 (m, 1H), 7.11 (d, J=4.8 Hz, 1H), 7.29-7.37 (m, 3H), 7.37-7.48 (m, 5H), 7.47-7.51 (m, 1H), 7.54 (t, J=7.8 Hz, 1H), 7.63 (d, J=4.8 Hz, 1H), 7.73-7.78 (m, 1H), 7.86 (s, 1H); MS (ES+): m/z 423.0 (100) [MH+].

Workup

  1. customcondensed into
  2. customThe tube was sealed
  3. customAfter excess NH3/i-PrOH was removed in vacuo
  4. customthe layers were separated
  5. extractionthe aqueous layer was extracted with CH2Cl2 (3×30 mL)
  6. washThe combined organic layers were washed with brine (3×30 mL)
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. filtrationThe crude material was purified by filtration through a plug of silica gel
  10. washeluting with 5% MeOH
  11. concentrationCH2Cl2 (400 mL), concentrated in vacuo

Sources & evidence

ORD record
ord-9f6049e015b3466abc0acd8d9f99781e
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

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