Phthalimide → HCID 178508461, compound

HRID 422603Notes

Reaction equation

HRID 422603 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C@H:27]3[CH2:32][CH2:31][C@H:30]([CH2:33]O)[CH2:29][CH2:28]3)=[N:9][C:10]=2[C:11]2[CH:20]=[C:19]3[C:14]([CH:15]=[CH:16][C:17]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:5]=[CH:6][N:7]=1.[C:35]1(=[O:45])[NH:39][C:38](=[O:40])[C:37]2=[CH:41][CH:42]=[CH:43][CH:44]=[C:36]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C@H:27]3[CH2:32][CH2:31][C@H:30]([CH2:33][N:39]4[C:35](=[O:45])[C:36]5[C:37](=[CH:41][CH:42]=[CH:43][CH:44]=5)[C:38]4=[O:40])[CH2:29][CH2:28]3)=[N:9][C:10]=2[C:11]2[CH:20]=[C:19]3[C:14]([CH:15]=[CH:16][C:17]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:5]=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776Triphenylphosphine2×HCID 5363146Diisopropyl azodicarboxylateHCID 178508462HCID 178508462, compound

Product 1

HCID 178508461HCID 178508461, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

trans-{4-[8-Amino-1-(2-phenylquinolin-7-yl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexyl}-methanol (290 mg, 0.47 mmol), phthalimide (82 mg, 0.56 mmol), and resin-bound triphenylphosphine (PS-Ph3P [Argonaut, 2.16 mmol/g]) (324 mg) were dissolved in 2.5 mL of THF, evacuated, placed under nitrogen atmosphere and charged with DIAD (0.11 mL, 0.56 mmol). After stirring for 16 h, the resin was filtered, washed with CH2Cl2 (5×) and concentrated to an orange-colored oil. The crude material was purified by silica gel column chromatography [Jones Flashmaster, 10 g/70 mL cartridge, eluting with 1% MeOH/CH2Cl2 to 2%˜7N NH3 in MeOH/CH2Cl2] to afford the desired product as a yellow solid; 1H NMR (CDCl3, 400 MHz) δ 1.17-1.29 (m, 2H), 1.60-1.61 (m, 1H), 1.87-2.07 (m, 4H), 2.12-2.23 (m, 2H), 2.92-3.02 (m, 1H), 3.64 (d, 2H, J=6.8 Hz), 5.25 (s, 2H), 7.11 (d, 1H, J=5.6 Hz), 7.24-7.26 (m, 1H), 7.45-7.49 (m, 1H), 7.52-7.56 (m, 2H), 7.72-7.75 (m, 2H), 7.86-7.95 (m, 5H), 8.17-8.20 (m, 2H), 8.25 (d, 1H, J=8.8 Hz), 8.38-8.39 (m, 1H); MS (ES+): m/z 579.0 [MH+]; HPLC: tR=2.9 min (Micromass Platform II, nonpolar—5 min).

Workup

  1. customevacuated
  2. filtrationthe resin was filtered
  3. washwashed with CH2Cl2 (5×)
  4. concentrationconcentrated to an orange-colored oil
  5. customThe crude material was purified by silica gel column chromatography [Jones Flashmaster, 10 g/70 mL cartridge, eluting with 1% MeOH/CH2Cl2 to 2%˜7N NH3 in MeOH/CH2Cl2]

Sources & evidence

ORD record
ord-e9ee84d645cb496d95a72491cd979c1a
Source dataset
uspto-grants-2012_01
Patent number
US08101613B2

Reaction notes

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