1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Methyl-2-{2-[4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-pentanoic acid benzyl ester

HRID 277194Notes

Reaction equation

HRID 277194 reaction equation
[C:1]1([CH3:21])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:20])[NH:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][C:17]([OH:19])=O)=[CH:12][CH:11]=1.[CH2:22]([O:29][C:30](=[O:37])[C@H:31]([CH2:33][CH:34]([CH3:36])C)[NH2:32])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[CH:38]1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C.O.C(N(CC)CC)C>[CH2:22]([O:29][C:30](=[O:37])[C:31]([CH3:38])([NH:32][C:17](=[O:19])[CH2:16][C:13]1[CH:12]=[CH:11][C:10]([NH:9][C:8]([NH:7][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[CH3:21])=[O:20])=[CH:15][CH:14]=1)[CH2:33][CH2:34][CH3:36])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 6451313Benzyl L-leucinateHCID 66052544-((((2-Methylphenyl)amino)carbonyl)amino)benzeneacetic acid

Product 1

HCID 69693211Methyl-2-{2-[4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-pentanoic acid benzyl esterYield 77.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a stirred solution of [4-(3-o-tolyl-ureido)-phenyl]-acetic acid (3.0 g), L-leucine benzyl ester (4.2 g), triethylamine (1.6 ml), and HOBT (1.6 g) in dry DMF (50 ml) at room temperature was added EDCI (2.4 g). After 16 h the mixture was poured into water (400 ml) and extracted with EtOAc (400 ml×2). The combined organics were washed with 5% citric acid (100 ml); saturated NaHCO3 (100 ml); water (100 ml), brine (100 ml); dried over MgSO4; filtered, and concentrated under reduced pressure to about 100 ml. The resulting suspension was filtered to give 4.0 g of the title compound as a white solid. MS [M+1]+488.2; 1H nmr (400 MHz, DMSO-d6) δ0.79 (d, J=6.4 Hz, 3H), 0.86 (d, J=6.4 Hz, 3H), 1.45-1.63 (m, 3H), 2.21 (s, 3H), 3.37 (s, 2H), 4.26-4.31 (m, 1H), 5.07 (s, 2H), 6.91 (t, 1H), 7.09-7.15 (m, 4H), 7.29-7.37 (m, 7H), 7.81 (d, 1H), 7.86 (s, 1H), 8.44 (d, 1H), 8.93 (s, 1H).

Workup

  1. extractionextracted with EtOAc (400 ml×2)
  2. washThe combined organics were washed with 5% citric acid (100 ml)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure to about 100 ml
  6. filtrationThe resulting suspension was filtered

Sources & evidence

ORD record
ord-e4148f90a0584aa9b756a5ddd1486a64
Source dataset
uspto-grants-2002_03
Patent number
US06355662B1

Reaction notes

Loading…