Ammonium Chloride → 2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzamide

HRID 1025877Notes

Reaction equation

HRID 1025877 reaction equation
COC(=O)C[NH:5][C:6](=[O:37])[C:7]1[CH:12]=[C:11]([Cl:13])[C:10]([O:14][C:15]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[C:21]([N:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[N:26]([CH:33]3[CH2:35][CH2:34]3)[CH2:25][CH2:24]2)=[O:22])=[CH:9][C:8]=1[Cl:36].[Cl-].[NH4+].ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC>CN(C)C=O>[Cl:36][C:8]1[CH:9]=[C:10]([O:14][C:15]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[C:21]([N:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[N:26]([CH:33]3[CH2:34][CH2:35]3)[CH2:25][CH2:24]2)=[O:22])[C:11]([Cl:13])=[CH:12][C:7]=1[C:6]([NH2:5])=[O:37]

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 53312194{2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzoylamino}-acetic acid methyl ester

Product 1

HCID 533112702,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzamideYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 0.10 g (0.21 mmol) 2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzoic acid (Example 29, intermediate) in 1 mL N,N-dimethylformamide were added 0.022 g (0.41 mmol) ammonium chloride, 0.028 g (0.21 mmol) 1-hydroxybenzotriazole, 0.07 mL N,N-diisopropylethylamine and 0.040 g (0.21 mmol) N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride. The resulting mixture was stirred at room temperature overnight, filtered over a syringe micro filter and purified on a preparative HPLC system (Phenomenex Gemini column) using a gradient of acetonitrile:water (containing 0.05% formic acid) (10:90 to 98:2) to afford 80 mg (80%) of the desired compound as a light brown solid. MS (ESI): m/z=483.098 [M+H]+.

Workup

  1. filtrationfiltered over a syringe
  2. filtrationmicro filter
  3. custompurified on a preparative HPLC system (Phenomenex Gemini column)

Sources & evidence

ORD record
ord-25e1297069a849c29e095a8800dacced
Source dataset
uspto-grants-2014_05
Patent number
US08729091B2

Reaction notes

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