HCID 11568520, compound → HCID 178511292, compound

HRID 244121Notes

Reaction equation

HRID 244121 reaction equation
[N:1]([CH2:4][CH:5]1[CH2:8][CH:7]([C:9]2[N:13]3[CH:14]=[CH:15][N:16]=[C:17]([NH2:18])[C:12]3=[C:11]([C:19]3[CH:28]=[C:27]4[C:22]([CH:23]=[CH:24][C:25]([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)=[N:26]4)=[CH:21][CH:20]=3)[N:10]=2)[CH2:6]1)=[N+]=[N-]>C(O)C.[Pd].CC([O-])=O.CC([O-])=O.[Pb+2]>[NH2:1][CH2:4][C@@H:5]1[CH2:6][C@H:7]([C:9]2[N:13]3[CH:14]=[CH:15][N:16]=[C:17]([NH2:18])[C:12]3=[C:11]([C:19]3[CH:28]=[C:27]4[C:22]([CH:23]=[CH:24][C:25]([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)=[N:26]4)=[CH:21][CH:20]=3)[N:10]=2)[CH2:8]1

Participants

4

Reactant 1

HCID 11568520HCID 11568520, compound

Product 1

HCID 178511292HCID 178511292, compound

Reagents, catalysts & solvents 2

HCID 131709914Lindlars catalystCatalystHCID 702EthanolSolvent

Procedure

3-[3-(Azidomethyl)cyclobutyl]-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-8-amine (0.81 mmol, 360 mg) was dissolved in hot ethanol (15 mL) and charged with Lindlar catalyst (0.14 mmol, 362 mg). The reaction mixture was purged with N2, evacuated and filled with H2. The reaction mixture was stirred under H2 for 16 h. The suspension was filtered through celite and the solvent was removed under reduced pressure. Part of the crude material (200 mg out of 300 mg) was purified by silica gel flush chromatography (Jones Flashmaster, 5 g/70 mL cartridge) eluting with 3% MeOH (7 N NH3) in DCM. The final compound was recrystallized from EtOAc and hexane to generate the desired product as a light yellow solid; 1H NMR (400 MHz, CDCl3) δ 8.42-8.41 (m, 1H), 8.27 (dd, J=8.0 Hz, 0.4 Hz, 1H), 8.21-8.19 (m, 2H), 7.95-7.92 (m, 3H), 7.57-7.48 (m, 3H), 7.19 (d, J=4.0 Hz, 1H), 7.11 (d, J=4.0 Hz, 1H), 5.20 (b, 2H), 3.73-3.69 (m, 1H), 2.81 (d, J=7.2 Hz, 2H), 2.66-2.62 (m, 2H), 2.58-2.48 (m, 1H), 2.36-2.30 (m, 2H); MS (ES+): m/z 421.13 (40) [MH+]; HPLC: tR=1.69 min (OpenLynx, polar—5 min).

Workup

  1. customThe reaction mixture was purged with N2
  2. customevacuated
  3. additionfilled with H2
  4. filtrationThe suspension was filtered through celite
  5. customthe solvent was removed under reduced pressure
  6. customPart of the crude material (200 mg out of 300 mg) was purified by silica gel
  7. customflush chromatography (Jones Flashmaster, 5 g/70 mL cartridge)
  8. washeluting with 3% MeOH (7 N NH3) in DCM
  9. customThe final compound was recrystallized from EtOAc and hexane
  10. customHPLC: tR=1.69 min (OpenLynx, polar—5 min)

Sources & evidence

ORD record
ord-2b4c010326da4769ab19f8e54d81a4a1
Source dataset
uspto-grants-2014_02
Patent number
US08653268B2

Reaction notes

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