Ethoxalyl chloride → Oxo-(4-{4-[6-(6-trifluoromethyl-pyridin-3-ylamino)-pyridin-3-yl]-phenyl}-piperidin-1-yl)-acetic acid ethyl ester

HRID 76050Notes

Reaction equation

HRID 76050 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:15]=[CH:16][C:17]([NH:20][C:21]4[CH:22]=[N:23][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:26]=4)=[N:18][CH:19]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.C(N(CC)C(C)C)(C)C.[CH2:40]([O:42][C:43](=[O:47])[C:44](Cl)=[O:45])[CH3:41]>C(Cl)Cl>[CH2:40]([O:42][C:43](=[O:47])[C:44](=[O:45])[N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:9]=[CH:10][C:11]([C:14]3[CH:19]=[N:18][C:17]([NH:20][C:21]4[CH:22]=[N:23][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:26]=4)=[CH:16][CH:15]=3)=[CH:12][CH:13]=2)[CH2:4][CH2:3]1)[CH3:41]

Participants

5

Reactant 3

HCID 20884Ethoxalyl chlorideHCID 81531DiisopropylethylamineHCID 66615908[5-(4-Piperidin-4-yl-phenyl)-pyridin-2-yl]-(6-trifluoromethyl-pyridin-3-yl)-amine hydrochloride

Product 1

HCID 66615852Oxo-(4-{4-[6-(6-trifluoromethyl-pyridin-3-ylamino)-pyridin-3-yl]-phenyl}-piperidin-1-yl)-acetic acid ethyl esterYield 99.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

[5-(4-Piperidin-4-yl-phenyl)-pyridin-2-yl]-(6-trifluoromethyl-pyridin-3-yl)-amine hydrochloride (200 mg, 0.46 mmol) was slurried in DCM (2 mL) and to it was added N,N-diisopropylethylamine (1.320 mL, 7.6 mmol). Chloro-oxo-acetic acid ethyl ester (0.076 mL, 0.69 mmol) was added dropwise, and the reaction was stirred for 18 hours. The reaction mixture was partitioned between EtOAc and water, washed with brine, dried with magnesium sulfate, filtered, and concentrated via rotary evaporation to obtain 229 mg of the title compound as a crude oil, which was taken to the next step without purification: MS (M+H)+499.2.

Workup

  1. customThe reaction mixture was partitioned between EtOAc and water
  2. washwashed with brine
  3. dry with materialdried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated via rotary evaporation

Sources & evidence

ORD record
ord-2fb03a62131246de88fa1fa3b14c31b5
Source dataset
uspto-grants-2014_09
Patent number
US08835451B2

Reaction notes

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