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

HRID 422587Notes

Reaction equation

HRID 422587 reaction equation
[NH3:1].C(=O)=O.[CH3:5][C:6]([CH3:8])=O.Cl[C:10]1[C:11]2[N:12]([C:16]([CH:29]3[CH2:32][CH2:31][CH2:30]3)=[N:17][C:18]=2[C:19]2[CH:28]=[C:27]3[C:22]([CH:23]=[CH:24][CH:25]=[N:26]3)=[CH:21][CH:20]=2)[CH:13]=[CH:14][N:15]=1.N.[CH3:34][CH:35](O)[CH3:36]>>[CH:29]1([CH:16]2[N:12]3[CH:13]=[CH:14][N:15]=[C:10]([NH2:1])[C:11]3=[C:18]([C:19]3[CH:28]=[C:27]4[C:22]([CH:23]=[CH:24][C:25]([C:6]5[CH:8]=[CH:36][CH:35]=[CH:34][CH:5]=5)=[N:26]4)=[CH:21][CH:20]=3)[NH:17]2)[CH2:32][CH2:31][CH2:30]1

Participants

5

Reactant 4

HCID 222AmmoniaHCID 183319422-Propanol, reaction products with ammonia, distn. residuesHCID 18522661Acetone cardiceHCID 576808877-(8-Chloro-3-cyclobutylimidazo[1,5-a]pyrazin-1-yl)-quinoline

Product 1

HCID 666761323-Cyclobutyl-1-(2-phenylquinolin-7-yl)-2H-imidazo[1,5-a]pyrazin-8-ylamine

Conditions

Temperature
110 °C

Procedure

Gaseous NH3 is condensed into a cooled (dry ice/acetone) solution of 7-(8-chloro-3-cyclobutylimidazo[1,5-a]pyrazin-1-yl)-quinoline (160.0 mg, 0.389 mmol) in 2M NH3/iPrOH (4 mL) in a pressure tube until the volume is doubled, then the tube is sealed and heated to 110° C. (bath temp.) for 15 h. The solvents are evaporated, and the crude material is chromatographed on silica gel [Jones Flashmaster, 10 g/70 mL cartridge, eluting with CH2Cl2 (1-7)→1% MeOH in CH2Cl2 (8-23)→2% MEOH in CH2Cl2 (24-46)] to obtain the title compound as yellow solid; 1H NMR (CDCl3, 400 MHz) δ 2.01-2.12 (m, 1H), 2.13-2.27 (m, 1H), 2.47-2.58 (m, 2H), 2.62-2.73 (m, 2H), 3.85 (quint, J=8.0 Hz, 1H), 6.00 (brs, 2H), 7.04 (d, J=5.4 Hz, 1H), 7.15 (d, J=5.4 Hz, 1H), 7.46-7.51 (m, 1H), 7.52-7.58 (m, 2H), 7.91 (dd, J=1.6, 8.4 Hz, 1H), 7.94 (d, J=8.4 Hz, 1H), 7.97 (d, J=8.0 Hz, 1H), 8.18-8.22 (m, 2H), 8.28 (d, J=8.4 Hz, 1H), 8.42 (d, J=0.8 Hz, 1H). 13C NMR (CDCl3, 100.6 MHz, DEPT135): δ=18.89 (−), 26.92 (2C, +), 31.50 (+), 106.62 (+), 114.32 (Cquart), 119.26 (+), 126.55 (Cquart), 127.56 (3C, +), 128.06 (+), 128.15 (+), 128.83 (2C, +), 129.44 (+), 129.67 (+), 134.56 (Cquart), 136.42 (Cquart), 136.53 (+), 139.44 (Cquart), 144.40 (Cquart), 148.18 (Cquart), 151.62 (Cquart), 157.94 (Cquart). MS (ES+): m/z 392.0 (100) [MH+]. HPLC: tR=1.7 min (MicromassZQ, nonpolar—5 min).

Workup

  1. customcondensed into
  2. customthe tube is sealed
  3. customThe solvents are evaporated
  4. customthe crude material is chromatographed on silica gel [Jones Flashmaster, 10 g/70 mL cartridge, eluting with CH2Cl2 (1-7)→1% MeOH in CH2Cl2 (8-23)→2% MEOH in CH2Cl2 (24-46)]

Sources & evidence

ORD record
ord-251179564c864484930be53aee5b6868
Source dataset
uspto-grants-2012_01
Patent number
US08101613B2

Reaction notes

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