N-methyl-2-pyrrolidone → 1-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-piperidine-4-carboxylic acid methyl ester

HRID 216269

Reaction equation

HRID 216269 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[C:15](Cl)[N:14]=[C:13]([O:18][CH3:19])[N:12]=2)[CH2:7][CH2:6]1)=[O:4].[Cl:20][C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=1[CH2:28][CH2:29][NH2:30].C(=O)(O)[O-].[Na+].CN1CCCC1=O>O>[CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[C:15]([NH:30][CH2:29][CH2:28][C:22]3[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:21]=3[Cl:20])[N:14]=[C:13]([O:18][CH3:19])[N:12]=2)[CH2:7][CH2:6]1)=[O:4]

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 1429382,4-Dichlorophenethylamine2×HCID 516892Sodium BicarbonateHCID 866157151-(6-Chloro-2-methoxy-pyrimidin-4-yl)-piperidine-4-carboxylic acid methyl ester

Product 1

HCID 690694161-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-piperidine-4-carboxylic acid methyl esterYield 44.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

In a tube is combined 1-(6-chloro-2-methoxy-pyrimidin-4-yl)-piperidine-4-carboxylic acid methyl ester [103 mg, 0.36 mmol], 2-(2,4-dichloro-phenyl)-ethylamine (0.163 mL, 1.08 mmol), sodium bicarbonate (181 mg, 2.16 mmol) and N-methylpyrrolidinone (2 mL). The mixture is heated at 140° C. for 12 h. Additional 2-(2,4-dichloro-phenyl)-ethylamine (0.2 mL, 1.33 mmol) is added and heating at 140° C. is continued for another 12 h. The mixture is diluted with water (30 mL) and extracted twice with EtOAc (30 mL). The organic extracts are washed twice with water (40 mL) and once with brine (30 mL), combined, dried over magnesium sulfate, filtered and concentrated. The residue is subjected to chromatography on silica gel eluting with 40% ethyl acetate:heptane to afford 1-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-piperidine-4-carboxylic acid methyl ester [70 mg, 44%] as a solid.

Workup

  1. customIn a tube is combined
  2. temperatureheating at 140° C.
  3. extractionextracted twice with EtOAc (30 mL)
  4. washThe organic extracts are washed twice with water (40 mL) and once with brine (30 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-247c3aba7db44a629a0d1f8a468a55a0
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Linked notes

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