Ammonia → HCID 11471056, compound

HRID 2373875Notes

Reaction equation

HRID 2373875 reaction equation
[NH3:1].Cl[C:3]1[C:4]2[N:5]([C:9]([CH:18]3[CH2:21][CH2:20][CH2:19]3)=[N:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:7][N:8]=1>N.CC(O)C>[CH:18]1([C:9]2[N:5]3[CH:6]=[CH:7][N:8]=[C:3]([NH2:1])[C:4]3=[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:10]=2)[CH2:21][CH2:20][CH2:19]1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 59852761HCID 59852761, compound

Product 1

HCID 11471056HCID 11471056, compoundYield 70%

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 8-chloro-3-cyclobutyl-1-phenylimidazo[1,5-a]pyrazine (602.9 mg, 2.125 mmol) in NH3/i-PrOH (2M, 15 mL) in a pressure tube until the volume had doubled. The tube was sealed and heated to 110° C. for 2 d. After excess NH3/i-PrOH was removed in vacuo, the residue was extracted with CH2Cl2 (3×30 mL), and the combined organic layers were washed with brine (3×30 mL), dried over anhydrous MgSO4, filtered, and concentrated. The material obtained (670 mg) was recrystallized from EtOAc, granting 393.3 mg (70%, 1.488 mmol) of the title compound, as pale pink crystals. The mother liquor was reduced ca. 50% in vacuo and again recrystallized from EtOAc, affording an additional 38.4 mg (7%, 0.145 mmol) of the title compound, as pink crystals, >99% pure by HPLC; mp. 164-166° C.; 1H NMR (CDCl3, 400 MHz) δ 1.98-2.09 (m, 1H), 2.11-2.23 (m, 1H), 2.44-2.54 (m, 2H), 2.58-2.70 (m, 2H), 3.82 (quint, J=8.4 Hz, 1H), 5.02 (s, br, —NH2), 7.05 (d, J=4.8 Hz, 1H), 7.12 (d, J=5.2 Hz, 1H), 7.38-7.43 (m, 1H), 7.46-7.53 (m, 2H), 7.65-7.70 (m, 2H). 13C NMR (CDCl3, 100.6 MHz, DEPT135): δ 18.87 (−), 26.94 (2C, −), 31.48 (+), 106.61 (+), 113.93 (Cquart), 127.43 (+), 128.08 (+), 128.81 (2C, +), 129.67 (2C, +), 134.87 (Cquart), 135.32 (Cquart), 143.90 (Cquart), 151.75 (Cquart). MS (ES+): m/z 265.2 (100) [MH+].

Workup

  1. customcondensed into
  2. customThe tube was sealed
  3. customAfter excess NH3/i-PrOH was removed in vacuo
  4. extractionthe residue was extracted with CH2Cl2 (3×30 mL)
  5. washthe combined organic layers were washed with brine (3×30 mL)
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe material obtained (670 mg)
  10. customwas recrystallized from EtOAc

Sources & evidence

ORD record
ord-611702740de24d44be20c56d544fc70f
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

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