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

HRID 1020033Notes

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][NH:22][CH2:21][CH2:20]2)=[O:18])[CH:11]=1)[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH:32]([CH3:34])[CH3:33]>CN(C=O)C>[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:22]([CH:32]([CH3:34])[CH3:33])[CH2:21][CH2:20]2)=[O:18])[CH:11]=1)[CH3:2]

Participants

Conditions

Temperature: 60 °C

Procedure

To a stirred solution of piperidine-4-carboxylic acid [6-(2-ethoxy-phenyl)-pyrimidin-4-yl]-amide (compound #1A) (0.35 g, 1.0 mmol) and potassium carbonate (0.17 g, 1.2 mmol) in DMF (4 ml) was added 2-bromopropane (0.10 ml, 1.07 mmol) at room temperature. The reaction mixture was heated at 60° C. for one hour. The progress of the reaction was monitored by TLC. The reaction mixture was poured onto ice water and extracted with ethyl acetate (3×100 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) and lyophilized to afford 1-isopropyl-piperidine-4-carboxylic acid [6-(2-ethoxy-phenyl)-pyrimidin-4-yl]-amide (compound #4A) (0.2 g, 51%) as a white solid.

Workup

additionThe reaction mixture was poured onto ice water
extractionextracted with ethyl acetate (3×100 ml)
customThe organic layers were separated
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe crude product was purified by preparative HPLC (C-18, AcN:H2O with 0.05% TFA)

Sources & evidence

ORD record: ord-ea747d8ed2bc4a5682d4524055d92619
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08716296B2

Reaction notes

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