1,2-Dichloroethane → HCID 66649123, compound

HRID 418332Notes

Reaction equation

HRID 418332 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[C:11]([CH2:15][CH2:16][C:17]([OH:19])=O)[CH:12]=[CH:13][CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:20]([C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][C:28]=1[O:29][CH3:30])[NH2:25])[CH3:21].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>O.CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][C:17](=[O:19])[NH:25][C:24]2[CH:26]=[CH:27][C:28]([O:29][CH3:30])=[C:22]([O:20][CH3:21])[CH:23]=2)[CH:10]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 227703,4-DimethoxyanilineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27609643-[3-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]propanoic Acid

Product 1

HCID 66649123HCID 66649123, compoundYield 110.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A reaction vial was charged with 3-(3-tert-butoxycarbonylamino-phenyl)-propionic acid (90 mg, 0.34 mmol), 3,4-dimethoxylaniline (90 mg, 0.59 mmol), EDC (100 mg, 0.64 mmol) and HOBt (100 mg, 0.74 mmol). DMF (2 mL) was added, followed by Hunig's base (0.3 mL, 1.72 mmol). The mixture was stirred at room temperature overnight, and then diluted with 10 mL water. The resulting mixture was extracted with 3×10 mL ethyl acetate. The organic layers were combined and washed with water and brine, dried with Na2SO4, and evaporated to give 150 mg crude {3-[2-(3,4-dimethoxy-phenylcarbamoyl)-ethyl]-phenyl}-carbamic acid tert-butyl ester which was used without purification. The ester intermediate was dissolved in dichloromethane (4 mL), and TFA (1 mL) was added. The resulting mixture was stirred at room temperature for 2 h, then concentrated to provide the product, 3-(3-amino-phenyl)-N-(3,4-dimethoxy-phenyl)-propionamide, as a TFA salt which was used without further purification (100 mg, 71% yield, 2 steps). This intermediate (100 mg, 0.33 mmol) was then combined with 3-(2-carboxy-ethyl)-piperidine-1-carboxylic acid tert-butyl ester (100 mg, 0.39 mmol), EDC (100 mg, 0.64 mmol) and HOBt (100 mg, 0.74 mmol) in a reaction vial. DMF (2 mL) was added, followed by Hunig's base (0.3 mL, 1.72 mmol). The mixture was stirred at room temperature overnight. The product was purified directly from the reaction mixture by preparative HPLC using an acetonitrile/water/formic acid gradient to afford the product, 3-(2-{3-[2-(3,4-dimethoxy-phenylcarbamoyl)-ethyl]-phenylcarbamoyl}-ethyl)-piperidine-1-carboxylic acid tert-butyl ester, as yellow oil (50 mg, 28% yield). This intermediate was then dissolved in dichloromethane (4 mL), and TFA (1 mL) was added. The resulting mixture was stirred at room temperature for 2 hours then concentrated to provide the title compound as a TFA salt (27 mg, 66% yield); MS, electrospray, 440 (M+H).

Workup

  1. customA reaction
  2. extractionThe resulting mixture was extracted with 3×10 mL ethyl acetate
  3. washwashed with water and brine
  4. dry with materialdried with Na2SO4
  5. customevaporated

Sources & evidence

ORD record
ord-6a9119e8c05149e0b9aae27eadc59658
Source dataset
uspto-grants-2012_01
Patent number
US08093266B2

Reaction notes

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