Acetic Acid → HCID 178522006、化合物

HRID 1376212ノート

反応式

HRID 1376212 の反応式
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

参加物

9

反応物 6

HCID 176Acetic AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 219476293,4-diamino-1-benzyl-1H-pyridin-2-oneHCID 446300243-{[(Benzyloxy)carbonyl]amino}cyclohexane-1-carboxylic acidHCID 68546350[3-(4-Amino-1-benzyl-2-oxo-1,2-dihydro-pyridin-3-ylcarbamoyl)-cyclohexyl]-carbamic acid benzyl ester

生成物 1

HCID 178522006HCID 178522006、化合物収率 45.6%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-3e17d94edc6340edb23e5eb0a6603a5f
出典データセット
uspto-grants-2007_01
特許番号
US07169926B1

反応ノート

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