Ammonium Chloride → 3-(4-Methoxy-quinolin-2-ylamino)-2-methyl-propionamide

HRID 2415133Notes

Reaction equation

HRID 2415133 reaction equation
[Cl-].[NH4+:2].C[Al](C)C.C[O:8][C:9](=O)[CH:10]([CH3:25])[CH2:11][NH:12][C:13]1[CH:22]=[C:21]([O:23][CH3:24])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]=1>C(Cl)Cl.C1(C)C=CC=CC=1>[CH3:24][O:23][C:21]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]=[C:13]([NH:12][CH2:11][CH:10]([CH3:25])[C:9]([NH2:2])=[O:8])[CH:22]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 16682925TrimethylaluminumHCID 698371313-(4-Methoxy-quinolin-2-ylamino)-2-methyl-propionic acid methyl ester

Product 1

HCID 226407303-(4-Methoxy-quinolin-2-ylamino)-2-methyl-propionamideYield 48%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Procedure

A slurry of ammonium chloride (0.38 g, 7.11 mmol) in dry methylene chloride (20 mL) at 0° C. was treated with trimethylaluminum (1 eq, 7.11 mmol, 3.6 mL of a 2M solution in toluene). The mixture was allowed to warm to room temperature over a period of two hours, at which time a solution of 3-(4-methoxy-quinolin-2-ylamino)-2-methyl-propionic acid methyl ester (0.33 eq, 2.37 mmol, 0.65 g) in dry methylene chloride (5 mL) was added. The solution stirred at room temperature for two hours, then was quenched slowly by addition of concentrated HCl (1 mL). After stirring for an additional 30 minutes, the mixture was diluted with 10% NaOH (30 mL) and brine (20 mL) and extracted into methylene chloride. The organic extracts were dried over Na2SO4, filtered and concentrated to an oil. Purification via column chromatography on silica (95:5 methylene chloride/methanolic ammonia) provided the product (0.29 g, 48%) as a white solid. [M+H]+ 260.

Workup

  1. additionwas added
  2. customwas quenched slowly by addition of concentrated HCl (1 mL)
  3. stirringAfter stirring for an additional 30 minutes
  4. additionthe mixture was diluted with 10% NaOH (30 mL) and brine (20 mL)
  5. extractionextracted into methylene chloride
  6. dry with materialThe organic extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to an oil
  9. customPurification via column chromatography on silica (95:5 methylene chloride/methanolic ammonia)

Sources & evidence

ORD record
ord-400a4decbdeb4e878363679ae45d5039
Source dataset
uspto-grants-2004_11
Patent number
US06818655B2

Reaction notes

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