Acetic Acid → HCID 178522006, compound

HRID 1376212Notes

Reaction equation

C(OC(NC1CCCC(C(O)=O)C1)=O)C1C=CC=CC=1.C1C=CC2N(O)N=NC=2C=1.NC1C(=O)N(CC2C=CC=CC=2)C=CC=1N.CCN=C=NCCCN(C)C.[CH2:58]([O:65][C:66](=[O:92])[NH:67][CH:68]1[CH2:73][CH2:72][CH2:71][CH:70]([C:74](=O)[NH:75][C:76]2[C:77](=[O:90])[N:78]([CH2:83][C:84]3[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=3)[CH:79]=[CH:80][C:81]=2[NH2:82])[CH2:69]1)[C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1.C(O)(=O)C>CN(C=O)C.O>[CH2:58]([O:65][C:66](=[O:92])[NH:67][CH:68]1[CH2:73][CH2:72][CH2:71][CH:70]([C:74]2[NH:75][C:76]3[C:77](=[O:90])[N:78]([CH2:83][C:84]4[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=4)[CH:79]=[CH:80][C:81]=3[N:82]=2)[CH2:69]1)[C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1

Participants

Conditions

Temperature: 0 °C

Procedure

3-Benzyloxycarbonylamino-cyclohexanecarboxylic acid (0.52 g, 1.86 mmol), TEA (0.41 g, 4.09 mmol), and HOBt (0.50 g, 3.72 mmol) were added sequentially to a solution of 3,4-diamino-1-benzyl-1H-pyridin-2-one (0.40 g, 1.86 mmol) in DMF (15 mL) at room temp. After the solution was cooled to 0° C., EDCI (0.71 g, 3.72 mmol) was added and the resulting solution was allowed to stir, with warming to room temp, for 17 h. The reaction mixture was diluted with water (10 mL) extracted with CH2Cl2, dried with MgSO4, and concentrated. The crude [3-(4-amino-1-benzyl-2-oxo-1,2-dihydro-pyridin-3-ylcarbamoyl)-cyclohexyl]-carbamic acid benzyl ester (0.57 g, 1.20 mmol) was dissolved in glacial acetic acid (7.21 g, 120.1 mmol), and heated at 120° C. for 2 days. After cooling to room temperature, the solvent was evaporated under reduced pressure and the cyclized product was purified by flash chromatography, eluting with 3% MeOH in CH2Cl2 to give [3-(5-benzyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl)-cyclohexyl]-carbamic acid benzyl ester (0.25 g, 30% for 2 steps). 1H-NMR (DMSO): δ 7.46 (m, 1H), 7.25–7.38 (m, 10H), 6.57 (m, 1H), 5.20 (s, 2H), 5.01 (s, 2H), 3.41 (m, 1H), 2.89 (m, 1H), 2.13 (m, 1H), 1.80 (m, 3H), 1.42 (m, 2H), 1.21 (m, 2H). MS: calculated for C27H28N4O3+H 457.2; found: 457.5.

Workup

temperaturewith warming to room temp, for 17 h
extractionextracted with CH2Cl2
dry with materialdried with MgSO4
concentrationconcentrated
temperatureheated at 120° C. for 2 days
temperatureAfter cooling to room temperature
customthe solvent was evaporated under reduced pressure
customthe cyclized product was purified by flash chromatography
washeluting with 3% MeOH in CH2Cl2

Sources & evidence

ORD record: ord-3e17d94edc6340edb23e5eb0a6603a5f
Source dataset: uspto-grants-2007_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07169926B1

Reaction notes

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