Phthalimide → HCID 59852832, compound

HRID 2373896Notes

Reaction equation

HRID 2373896 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C:25]3[CH:26]=[C:27]([CH2:31]O)[CH:28]=[CH:29][CH:30]=3)=[N:9][C:10]=2[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:12]=2)[CH:5]=[CH:6][N:7]=1.[C:33]1(=[O:43])[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:35](=[O:42])[NH:34]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=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:25]3[CH:26]=[C:27]([CH:28]=[CH:29][CH:30]=3)[CH2:31][N:34]3[C:35](=[O:42])[C:36]4[C:41](=[CH:40][CH:39]=[CH:38][CH:37]=4)[C:33]3=[O:43])=[N:9][C:10]=2[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:12]=2)[CH:5]=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 11293122HCID 11293122, compound

Product 1

HCID 59852832HCID 59852832, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution/suspension of {3-[8-amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-phenyl}-methanol (312 mg, 0.737 mmol), isoindole-1,3-dione (130 mg, 0.885 mmol), and PS-PPh3 (loading 2.12 mmol/g; 696 mg, 1.47 mmol) in anhydrous THF (15 mL), cooled to 0° C., DIAD (218 μL, 224 mg, 1.11 mmol) was added dropwise, under N2 atmosphere. After 10 min, the cooling bath was removed and the reaction mixture stirred at ambient temperature for 3d. The resin was filtered off on a glass frit (porosity M) and washed with large volumes of THF and then CH2Cl2. The filtrate was concentrated, adsorbed onto Hydromatrix, and the crude material (0.6843 g) was purified by chromatography on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with MeOH:CH2Cl2 0.5%→3%], yielding the title compound as a yellow solid. Sample contains ≈0.3 eq. of reduced DIAD by 1H NMR; 1H NMR (CDCl3, 400 MHz) δ 4.94 (s, 2H), 5.07 (s, 2H), 5.16 (s, 2H), 7.07 (ddd, J=8.4, 2.8, 1.2 Hz, 1H), 7.11 (d, J=5.2 Hz, 1H), 7.28-7.33 (m, 3H), 7.33-7.36 (m, 1H), 7.37-7.43 (m, 2H), 7.43-7.47 (m, 2H), 7.50 (t, J=7.6 Hz, 1H), 7.53-7.56 (m, 1H), 7.62 (d, J=5.2 Hz, 1H), 7.72 (dd, J=5.6, 2.8 Hz, 2H), 7.74-7.77 (m, 1H), 7.86 (dd, J=5.2, 3.2 Hz, 2H), 7.92 (s, 1H); MS (ES+): m/z 552.3 (100) [MH+].

Workup

  1. customthe cooling bath was removed
  2. filtrationThe resin was filtered off on a glass frit (porosity M)
  3. washwashed with large volumes of THF
  4. concentrationThe filtrate was concentrated
  5. customthe crude material (0.6843 g) was purified by chromatography on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with MeOH:CH2Cl2 0.5%→3%]

Sources & evidence

ORD record
ord-ad6b23facd88459b9efe92d338ebd59f
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

Loading…