Cyclopropanecarbonyl chloride → [2'-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-4'-(6-ethoxy-pyridin-3-yl)-6-methoxy-biphenyl-3-yl]-acetic acid ethyl ester

HRID 1625668Notes

Reaction equation

HRID 1625668 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:34])[CH2:6][C:7]1[CH:8]=[C:9]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:22]=[N:23][C:24]([O:27][CH2:28][CH3:29])=[CH:25][CH:26]=3)=[CH:17][C:16]=2[CH2:30][NH:31][CH2:32][CH3:33])[C:10]([O:13][CH3:14])=[CH:11][CH:12]=1)[CH3:3].C(N(CC)C(C)C)(C)C.[CH:44]1([C:47](Cl)=[O:48])[CH2:46][CH2:45]1>ClCCl.O>[CH2:2]([O:4][C:5](=[O:34])[CH2:6][C:7]1[CH:8]=[C:9]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:22]=[N:23][C:24]([O:27][CH2:28][CH3:29])=[CH:25][CH:26]=3)=[CH:17][C:16]=2[CH2:30][N:31]([C:47]([CH:44]2[CH2:46][CH2:45]2)=[O:48])[CH2:32][CH3:33])[C:10]([O:13][CH3:14])=[CH:11][CH:12]=1)[CH3:3]

Participants

6

Reactant 3

HCID 77637Cyclopropanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 66958971[4'-(6-Ethoxy-pyridin-3-yl)-2'-ethylaminomethyl-6-methoxy-biphenyl-3-yl]-acetic acid ethyl ester hydrochloride

Product 1

HCID 58149167[2'-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-4'-(6-ethoxy-pyridin-3-yl)-6-methoxy-biphenyl-3-yl]-acetic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To [4′-(6-ethoxy-pyridin-3-yl)-2′-ethylaminomethyl-6-methoxy-biphenyl-3-yl]-acetic acid ethyl ester hydrochloride (0.357 g, 0.736 mmol) and N,N-diisopropylethylamine (0.75 mL, 4.3 mmol) in dichloromethane (4 mL) was added cyclopropanecarbonyl chloride (0.074 mL, 0.814 mmol), and the reaction was stirred at room temperature. Once no starting material was seen by analytical LCMS, the mixture was diluted with dichloromethane and water, and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated, and the residue was purified by silica gel chromatography (ethyl acetate in hexanes gradient) to give the title compound.

Workup

  1. extractionthe aqueous layer was extracted with dichloromethane
  2. dry with materialThe combined organic layers were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customthe residue was purified by silica gel chromatography (ethyl acetate in hexanes gradient)

Sources & evidence

ORD record
ord-22270dadad8d4bc799ae58bd40f6ed58
Source dataset
uspto-grants-2014_07
Patent number
US08785393B2

Reaction notes

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