Aniline → HCID 68928484, compound

HRID 2373925Notes

Reaction equation

HRID 2373925 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([C:8]([CH:25]3[CH2:30][CH2:29][CH:28]([CH2:31][O:32]S(C4C=CC(C)=CC=4)(=O)=O)[CH2:27][CH2:26]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.[NH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.CN(C=[O:54])C>CO>[CH:31]([OH:32])=[O:54].[CH2:18]([O:17][C:13]1[CH:12]=[C:11]([C:10]2[N:9]=[C:8]([CH:25]3[CH2:30][CH2:29][CH:28]([CH2:31][NH:43][C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)[CH2:27][CH2:26]3)[N:4]3[CH:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=23)[CH:16]=[CH:15][CH:14]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 6115AnilineHCID 6228DimethylformamideHCID 57777531HCID 57777531, compound

Product 1

HCID 68928484HCID 68928484, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of toluene-4-sulfonic acid 4-[8-amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexylmethyl ester (29 mg, 0.05 mmol) in DMF (0.5 ml) was added aniline (23 μl, 0.25 mmol). The reaction was irradiated in the microwave (200 W, 150° C., 10 m), then evaporated to dryness. The crude reaction product was dissolved in MeOH (2 ml) and added to a pre-wetted MCX cartridge (6 ml/500 mg). The cartridge was washed with MeOH (10 ml) and the product was then eluted using 1% NH3 in MeOH (15 ml). The product was further purified using mass-directed HPLC, to give 1-(3-benzyloxy-phenyl)-3-(4-phenylaminomethyl-cyclohexyl)-imidazo[1,5-a]pyrazin-8-ylamine formic acid salt (7.8 mg, 31%) as an off-white solid: 1H NMR (400 MHz, CD3OD) δ 8.25 (s, 1H), 7.60 (d, 1H, J=5.5 Hz), 7.48-7.41 (m, 3H), 7.36 (t, 2H, J=7.3 Hz), 7.33-7.27 (m, 1H), 7.25-7.22 (m, 1H), 7.18 (d, 1H, J=7.4 Hz), 7.13 (dd, 1H, J=5.5 Hz, 2.3 Hz), 7.08 (t, 2H, J=7.8 Hz), 6.97 (d, 1H, J=5.5 Hz), 6.63 (d, 2H, J=7.4 Hz), 6.58 (t, 1H, J=7.4 Hz), 5.16 (s, 2H), 3.12 (m, 1H), 3.00 (d, 2H, J=6.7 Hz), 2.06 (br. d, 4H, J=11.7 Hz), 1.88-1.70 (m, 3H), 1.30-1.22 (m, 2H), 3H not observed (NH2 and NH); MS (ES+) m/z 504.24 [MH+] at Rt 3.47 min.

Workup

  1. customThe reaction was irradiated in the microwave (200 W, 150° C., 10 m)
  2. customevaporated to dryness
  3. customThe crude reaction product
  4. additionadded to a pre-wetted MCX cartridge (6 ml/500 mg)
  5. washThe cartridge was washed with MeOH (10 ml)
  6. washthe product was then eluted
  7. customThe product was further purified

Sources & evidence

ORD record
ord-e03f19e0890b449a82d5b26c60ad5967
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

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