1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 178462502, compound

HRID 2244807Notes

Reaction equation

HRID 2244807 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH:14]([C:18](O)=O)[CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.[NH2:31][C:32]1[C:33](=[O:41])[N:34]([CH2:39][CH3:40])[CH:35]=[CH:36][C:37]=1[NH2:38].CCN=C=NCCCN(C)C>CN(C=O)C.O>[CH2:1]([O:8][C:9](=[O:10])[NH:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH:14]([C:18]2[NH:31][C:32]3[C:33](=[O:41])[N:34]([CH2:39][CH3:40])[CH:35]=[CH:36][C:37]=3[N:38]=2)[CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 446300243-{[(Benzyloxy)carbonyl]amino}cyclohexane-1-carboxylic acidHCID 451166373,4-diamino-1-ethyl-1H-pyridin-2-one

Product 1

HCID 178462502HCID 178462502, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

In a 100 mL round bottom flask, 3-benzyloxycarbonylamino-cyclohexanecarboxylic acid (0.53 g, 1.96 mmol), TEA (0.44 g, 4.31 mmol), and HOBt (0.53 g, 3.92 mmol) were added sequentially to a solution of 3,4-diamino-1-ethyl-1H-pyridin-2-one (0.30 g, 1.96 mmol) in DMF (15 mL) at room temperature. The solution was then cooled to 0° C., EDCI (0.75 g, 3.92 mmol) was added, and the reaction mixture was allowed to stir, with warming to room temperature. After stirring for 17 h, the reaction mixture was diluted with water (10 mL) and extracted with CH2Cl2. The combined extracts were dried with MgSO4, and concentrated. The solid was rinsed with Et2O to give [3-(5-ethyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl)-cyclohexyl]-carbamic acid benzyl ester (0.68 g, 84% yield). The intermediate amide (0.43 g, 1.04 mmol) was dissolved in glacial acetic acid (6.26 g, 104.2 mmol) and heated at 120° C. for 2 days. After cooling to room temperature, the solvent was removed in vacuo and the crude product was purified by flash chromatography eluting with 3% MeOH in CH2Cl2 to give [3-(5-ethyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl)-cyclohexyl]-carbamic acid benzyl ester (0.22 g, 54% yield). 1H-NMR (DMSO): δ 7.35 (m, 6H), 6.53 (m, 1H), 5.01 (s, 2H), 3.99 (m, 2H), 3.43 (m, 1H), 2.86 (m, 1H), 2.07 (m, 1H), 1.83 (m, 3H), 1.42 (m, 3H), 1.20 (m, 3H), 1.17 (m, 1H). MS: calculated for C22H26N4O3+H 395.2; found: 395.4.

Workup

  1. temperaturewith warming to room temperature
  2. stirringAfter stirring for 17 h
  3. extractionextracted with CH2Cl2
  4. dry with materialThe combined extracts were dried with MgSO4
  5. concentrationconcentrated
  6. washThe solid was rinsed with Et2O

Sources & evidence

ORD record
ord-385a6b48f11e4ff0a56af2eb8a836b4c
Source dataset
uspto-grants-2010_03
Patent number
US07678909B1

Reaction notes

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