1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57874474, compound

HRID 1093864Notes

Reaction equation

HRID 1093864 reaction equation
CCN(C(C)C)C(C)C.[C:10]1([N:16]2[CH:20]=[C:19]([C:21]([NH:23][CH2:24][C:25]([OH:27])=O)=[O:22])[N:18]=[CH:17]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH:50]1[CH2:53][CH:52]([O:54][C:55]2[CH:56]=[C:57]([CH:60]=[CH:61][C:62]=2[CH3:63])[C:58]#[N:59])[CH2:51]1>CN(C=O)C>[C:58]([C:57]1[CH:60]=[CH:61][C:62]([CH3:63])=[C:55]([CH:56]=1)[O:54][CH:52]1[CH2:51][N:50]([C:25](=[O:27])[CH2:24][NH:23][C:21]([C:19]2[N:18]=[CH:17][N:16]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:20]=2)=[O:22])[CH2:53]1)#[N:59]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66591819[(1-phenyl-1H-imidazole-4-carbonyl)-amino]-acetic acidHCID 66592005HCID 66592005, compound

Product 1

HCID 57874474HCID 57874474, compoundYield 18.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (193.9 mg, 1.5 mmol) was added to a stirred solution of [(1-phenyl-1H-imidazole-4-carbonyl)-amino]-acetic acid (prepared from Intermediate 68 by means of Step 3 of the General Scheme) (92 mg, 0.37 mmol) in DMF (3 mL) followed by HOBt (53.2 mg, 0.39 mmol) and EDCI (75.5 mg, 0.39 mmol). After 2 minutes of stirring, 3-(azetidin-3-yloxy)-4-methyl-benzonitrile hydrochloride (prepared by the method used for the synthesis of Intermediate 71) (84 mg, 0.37 mmol) was added and the resulting mixture was stirred at ambient temperature overnight. Partitioning with cold water and ethyl acetate and concentration of the organic layer after drying over sodium sulfate afforded a residue which was purified by preparative HPLC to afford 29 mg (18.7% Yield) of 1-phenyl-1H-imidazole-4-carboxylic acid {2-[3-(5-cyano-2-methyl-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 416, 98.6%. 1H NMR (300 MHz, DMSO-d6): δ 8.38 (d, 1H), 8.28 (d, 1H), 8.12 (t, 1H), 7.7 (d, 2H), 7.5 (t, 2H), 7.38 (m, 3H), 7.16 (s, 1H), 5.2 (m, 1H), 4.7 (t, 1H), 4.4 (m, 1H), 4.2 (m, 1H), 3.8 (m, 3H).

Workup

  1. additionwas added
  2. stirringthe resulting mixture was stirred at ambient temperature overnight
  3. customPartitioning with cold water and ethyl acetate and concentration of the organic layer
  4. dry with materialafter drying over sodium sulfate
  5. customafforded a residue which
  6. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-d976858ba68344e9825362252bbfa79b
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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