1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57920122, compound

HRID 19366Notes

Reaction equation

HRID 19366 reaction equation
[CH:1]12[CH:7]([CH2:8][CH:9]([N:13]3[CH2:17][C:16]([O:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[Cl:25])=[CH:15][C:14]3=[O:26])[C:10](O)=[O:11])[CH:4]([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.[CH3:27]N(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.Cl.[OH:49][C@@H:50]([CH2:80]O)[CH2:51][N:52]1[CH:56]=[CH:55][C:54]([NH:57]C(=O)[C@@H](N2CC(OC3C=CC=C(Cl)C=3Cl)=CC2=O)CC(C)C)=[N:53]1>ClCCl>[CH:1]12[CH:7]([CH2:8][CH:9]([N:13]3[CH2:17][C:16]([O:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[Cl:25])=[CH:15][C:14]3=[O:26])[C:10]([NH:57][C:54]3[CH:55]=[CH:56][N:52]([CH2:51][C:50]([OH:49])([CH3:80])[CH3:27])[N:53]=3)=[O:11])[CH:4]([CH2:5][CH2:6]1)[CH2:3][CH2:2]2

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 668951463-Bicyclo[2.2.1]hept-7-yl-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acidHCID 66899094HMS5552 HCl

Product 1

HCID 57920122HCID 57920122, compoundYield 61.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

In a round bottom flask under argon was placed 3-bicyclo[2.2.1]hept-7-yl-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acid (32 mg, 0.085 mmol) in dichloromethane (5 mL). To this mixture was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (16 μL, 0.094 mmol) and 1-hydoxybenzotriazole (12 mg, 0.089 mmol) and stirred at 25° C. for 2 h. After this time, 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared as in US20080021032, Example 80, 16 mg, 0.102 mmol) was added and stirred for 16 h at 25° C. The reaction was diluted with dichloromethane (10 mL) and washed with a 1N aqueous hydrochloric acid solution (10 mL), water (10 mL), a saturated aqueous sodium bicarbonate solution (10 mL), dried over magnesium sulfate and concentrated in vacuo. Purification by AnaLogix IntelliFlash flash chromatography (4 g column, 20% ethyl acetate/hexanes to 80% ethyl acetate/hexanes) afforded 3-bicyclo[2.2.1]hept-7-yl-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide (27 mg, 61%) as yellow foam: HR-ES-MS m/z calculated for C27H33N4O4Cl [M+H]+ 513.2263, observed 513.2263; 1H NMR (300 MHz, CDCl3) δ ppm 1.15 (s, 6H), 1.15-1.31 (m, 4H), 1.43-1.59 (m, 3H), 1.65 (d, J=8.5 Hz, 2H), 1.70-1.87 (m, 1H), 1.90-2.09 (m, 3H), 2.80 (br. s., 1H), 3.93 (s, 2H), 4.16 (d, J=18.1 Hz, 1H), 4.32 (d, J=18.1 Hz, 1H), 4.76 (t, J=7.7 Hz, 1H), 4.89 (s, 1H), 6.70 (s, 1H), 7.17-7.25 (m, 1H), 7.27-7.37 (m, 3H), 7.48 (d, J=8.2 Hz, 1H), 8.74 (br. s., 1H).

Workup

  1. customIn a round bottom flask under argon was placed
  2. stirringstirred for 16 h at 25° C
  3. washwashed with a 1N aqueous hydrochloric acid solution (10 mL), water (10 mL)
  4. dry with materiala saturated aqueous sodium bicarbonate solution (10 mL), dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification by AnaLogix IntelliFlash flash chromatography (4 g column, 20% ethyl acetate/hexanes to 80% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-d0bf0aa40c0241caaa7bc2e3fb02a0f2
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

Loading…