Formaldehyde → 1-Ethyl-piperidine-4-carboxylic acid [6-(2-ethoxy-phenyl)-pyrimidin-4-yl]-amide

HRID 1020031Notes

Reaction equation

HRID 1020031 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[N:15]=[CH:14][N:13]=[C:12]([NH:16][C:17]([CH:19]2[CH2:24][CH2:23]N[CH2:21][CH2:20]2)=[O:18])[CH:11]=1)[CH3:2].[CH2:25]=O.[BH3-][C:28]#[N:29].[Na+]>>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[N:15]=[CH:14][N:13]=[C:12]([NH:16][C:17]([CH:19]2[CH2:24][CH2:23][N:29]([CH2:28][CH3:25])[CH2:21][CH2:20]2)=[O:18])[CH:11]=1)[CH3:2]

Participants

4

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 59508999Piperidine-4-carboxylic acid [6-(2-ethoxy-phenyl)-pyrimidin-4-yl]-amide

Product 1

HCID 595089481-Ethyl-piperidine-4-carboxylic acid [6-(2-ethoxy-phenyl)-pyrimidin-4-yl]-amideYield 66%

Procedure

To a stirred mixture of piperidine-4-carboxylic acid [6-(2-ethoxy-phenyl)-pyrimidin-4-yl]-amide (compound #1A) (0.28 g, 0.86 mmol) and 33% formalin solution (0.045 ml) in 10 ml of AcN:MeOH:H2O (2:1:1) at 0° C. was added NaCNBH3 (0.13 g, 2.1 mmol). The reaction mixture was stirred at room temperature for 30 minand extracted with ethyl acetate (3×20 ml). The organic layers were separated, combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by preparative HPLC (C-18, AcN:H2O with 0.05% TFA) to afford 1-ethyl-piperidine-4-carboxylic acid [6-(2-ethoxy-phenyl)-pyrimidin-4-yl]-amide (compound #2A) (0.195 g, 66%) as a white solid.

Workup

  1. extractionextracted with ethyl acetate (3×20 ml)
  2. customThe organic layers were separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by preparative HPLC (C-18, AcN:H2O with 0.05% TFA)

Sources & evidence

ORD record
ord-db0dcae422f445fba82f431aa0664225
Source dataset
uspto-grants-2014_05
Patent number
US08716296B2

Reaction notes

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