Potassium Iodide → tert-butyl 3-(2-(2-(2-(((6-((4-(piperidin-1-yl)-2-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)-phenyl)carbamoyl)pyridin-2-yl)methyl)(methyl)amino)ethoxy)ethoxy)ethoxy)propanoate

HRID 2409852Notes

Reaction equation

HRID 2409852 reaction equation
Cl[CH2:2][C:3]1[N:8]=[C:7]([C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[CH:14][C:13]=2[C:24](=[O:41])[NH:25][C:26]2[CH:30]=[CH:29][N:28]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=3)[N:27]=2)=[O:10])[CH:6]=[CH:5][CH:4]=1.[CH3:42][NH:43][CH2:44][CH2:45][O:46][CH2:47][CH2:48][O:49][CH2:50][CH2:51][O:52][CH2:53][CH2:54][C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56].[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[N:18]1([C:15]2[CH:16]=[CH:17][C:12]([NH:11][C:9]([C:7]3[N:8]=[C:3]([CH2:2][N:43]([CH3:42])[CH2:44][CH2:45][O:46][CH2:47][CH2:48][O:49][CH2:50][CH2:51][O:52][CH2:53][CH2:54][C:55]([O:57][C:58]([CH3:60])([CH3:59])[CH3:61])=[O:56])[CH:4]=[CH:5][CH:6]=3)=[O:10])=[C:13]([C:24](=[O:41])[NH:25][C:26]3[CH:30]=[CH:29][N:28]([C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=4)[N:27]=3)[CH:14]=2)[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 53662991Methylamino-PEG3-t-butyl esterHCID 665882706-(chloromethyl)-N-(4-(piperidin-1-yl)-2-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)phenyl)picolinamide

Product 1

HCID 66588149tert-butyl 3-(2-(2-(2-(((6-((4-(piperidin-1-yl)-2-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)-phenyl)carbamoyl)pyridin-2-yl)methyl)(methyl)amino)ethoxy)ethoxy)ethoxy)propanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Into a 50-mL round bottom flask, was placed a solution of 6-(chloromethyl)-N-(4-(piperidin-1-yl)-2-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)phenyl)picolinamide (170 mg, 0.29 mmol, 1.00 equiv) in N,N-dimethylformamide (5 mL), tert-butyl 3-(2-(2-(2-(methylamino)ethoxy)ethoxy)ethoxy)-propanoate (255 mg, 0.88 mmol, 3.00 equiv), potassium iodide (24.2 mg, 0.15 mmol, 0.50 equiv), and potassium carbonate (79.5 mg, 0.58 mmol, 1.97 equiv). The resulting solution was stirred for 2.5 h at 70° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting solution was diluted with 50 mL of water. The resulting solution was extracted with 3×50 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3×50 mL of brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. This resulted in

Workup

  1. customInto a 50-mL round bottom flask, was placed
  2. extractionThe resulting solution was extracted with 3×50 mL of ethyl acetate
  3. washThe resulting mixture was washed with 3×50 mL of brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThis resulted in

Sources & evidence

ORD record
ord-b950864171d8484d819b7ede8d7c4e34
Source dataset
uspto-grants-2014_08
Patent number
US08815910B2

Reaction notes

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