1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 66899251, compound

HRID 19350Notes

Reaction equation

HRID 19350 reaction equation
[Cl:1][C:2]1[CH:24]=[CH:23][CH:22]=[CH:21][C:3]=1[O:4][C:5]1[CH2:9][N:8]([CH:10]([CH2:14][CH2:15][C:16]([CH3:19])([CH3:18])[CH3:17])[C:11]([OH:13])=O)[C:7](=[O:20])[CH:6]=1.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[CH3:46][C:47]1([CH3:59])[O:51][C@H:50]([CH2:52][N:53]2[CH:57]=[CH:56][C:55]([NH2:58])=[N:54]2)[CH2:49][O:48]1>ClCCl>[CH3:46][C:47]1([CH3:59])[O:51][C@H:50]([CH2:52][N:53]2[CH:57]=[CH:56][C:55]([NH:58][C:11](=[O:13])[CH:10]([N:8]3[CH2:9][C:5]([O:4][C:3]4[CH:21]=[CH:22][CH:23]=[CH:24][C:2]=4[Cl:1])=[CH:6][C:7]3=[O:20])[CH2:14][CH2:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[N:54]2)[CH2:49][O:48]1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 59344941(R)-1-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amineHCID 668953032-[4-(2-Chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5-dimethyl-hexanoic acid

Product 1

HCID 66899251HCID 66899251, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

In a round bottom flask under argon was placed 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5-dimethyl-hexanoic acid (32 mg, 0.091 mmol) in dichloromethane (3 mL). To this mixture was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (20 μL, 0.10 mmol) and 1-hydoxybenzotriazole (13 mg, 0.096 mmol) and stirred at 25° C. for 2 h. After this time period, 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 21 mg, 0.109 mmol) was added and stirred for 16 h at 25° C. After this time, the mixture was diluted with dichloromethane (10 mL) and washed with a 1N aqueous hydrochloric acid solution (10 mL), water (10 mL) and a saturated aqueous sodium bicarbonate solution (10 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by AnaLogix IntelliFlash flash chromatography (4 g column, 30% ethyl acetate/hexanes to 100% ethyl acetate/hexanes) afforded 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5-dimethyl-hexanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (14 mg, 29%) as a colorless oil.

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. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by AnaLogix IntelliFlash flash chromatography (4 g column, 30% ethyl acetate/hexanes to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-bedd9d690b5940938fd6adf98919bae8
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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