HCID 59852832, compound → HCID 11154395, compound

HRID 2373895Notes

Reaction equation

HRID 2373895 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C:25]3[CH:26]=[C:27]([CH:40]=[CH:41][CH:42]=3)[CH2:28][N:29]3C(=O)C4C(=CC=CC=4)C3=O)=[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(Cl)Cl>[NH2:29][CH2:28][C:27]1[CH:26]=[C:25]([C:8]2[N:4]3[CH:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]3=[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH:12]=3)[N:9]=2)[CH:42]=[CH:41][CH:40]=1

Participants

3

Reactant 1

HCID 59852832HCID 59852832, compound

Product 1

HCID 11154395HCID 11154395, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-{3-[8-amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]-benzyl}-isoindole-1,3-dione (328 mg, 0.594 mmol) in CH2Cl2 (4 mL), N2H4 (56 μL, 57 mg, 1.78 mmol) was added and the reaction was vortexed at rt for 17 h, under N2 atmosphere. Additional N2H4 (40 μL, 41 mg, 1.27 mmol) and CH2Cl2 (10 mL) were added and vortexing was continued for 3 d. The suspension was filtered, the solid was washed extensively with CH2Cl2, and the filtrate was concentrated in vacuo. The crude material (273 mg) was purified by chromatography on silica gel [Jones Flashmaster, 5 g/25 mL cartridge, eluting with MeOH (7N NH3):CH2Cl2 5%→10%], affording 107.4 mg (43%, 0.255 mmol) of the title compound, as a yellow solid, containing 0.18 eq. of DMF. Mixed fractions were also collected, giving an additional 67.4 mg (max. 16%, 0.159 mmol) of the title compound, as a yellow solid, containing 0.8 eq. of DMF; 1H NMR (CDCl3, 400 MHz) δ 1.88 (s, br, —NH2), 3.97 (s, 2H), 5.15 (s, 4H), 7.05-7.09 (m, 1H), 7.10 (d, J=4.8 Hz, 1H), 7.29-7.47 (m, 9H), 7.51 (t, J=7.8 Hz, 1H), 7.63 (d, J=5.2 Hz, 1H), 7.69 (d, J=7.6 Hz, 1H), 7.81 (s, 1H); MS (ES+): m/z 422.0 (14) [MH+].

Workup

  1. waitvortexing was continued for 3 d
  2. filtrationThe suspension was filtered
  3. washthe solid was washed extensively with CH2Cl2
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe crude material (273 mg) was purified by chromatography on silica gel [Jones Flashmaster, 5 g/25 mL cartridge, eluting with MeOH (7N NH3):CH2Cl2 5%→10%]

Sources & evidence

ORD record
ord-d34f48540c9c4632a742160ae9a98081
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

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