Water → N-((5-((2-(pyrimidin-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide

HRID 1049348Notes

Reaction equation

HRID 1049348 reaction equation
[CH3:1][C:2]([CH3:7])([CH3:6])[C:3]([NH2:5])=[O:4].C(Cl)(=O)[C:9](Cl)=[O:10].[N:14]1[CH:19]=[C:18]([C:20]2[CH:25]=[C:24]([O:26][C:27]3[CH:28]=[CH:29][C:30]([NH2:33])=[N:31][CH:32]=3)[CH:23]=[CH:22][N:21]=2)[CH:17]=[N:16][CH:15]=1.O>ClCCCl.C1COCC1>[N:14]1[CH:19]=[C:18]([C:20]2[CH:25]=[C:24]([O:26][C:27]3[CH:28]=[CH:29][C:30]([NH:33][C:9]([NH:5][C:3](=[O:4])[C:2]([CH3:7])([CH3:6])[CH3:1])=[O:10])=[N:31][CH:32]=3)[CH:23]=[CH:22][N:21]=2)[CH:17]=[N:16][CH:15]=1

Participants

7

Reactant 4

HCID 962WaterHCID 12957TrimethylacetamideHCID 65578Oxalyl chlorideHCID 904028755-((2-(Pyrimidin-5-yl)pyridin-4-yl)oxy)pyridin-2-amine

Product 1

HCID 90403186N-((5-((2-(pyrimidin-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamideYield 70%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2,2,2-trimethylacetamide (0.048 g, 0.475 mmol) in DCE (3 mL) was treated with oxalyl chloride (0.042 mL, 0.475 mmol), stirred at RT for 1 h, then heated at 75° C. for 1 h. The mixture was cooled to RT, treated with a solution 5-((2-(pyrimidin-5-yl)pyridin-4-yl)oxy)pyridin-2-amine (0.063 g, 0.237 mmol) and TEA (0.099 mL, 0.712 mmol) in THF (3 mL) and stirred at RT for 1 h. The mixture was treated with water, extracted with DCM (2×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford N-((5-((2-(pyrimidin-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (65 mg, 70%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.23 (s, 1H), 10.44 (s, 1H), 9.41 (s, 2H), 9.24 (s, 1H), 8.62 (d, J=5.7 Hz, 1H), 8.30 (d, J=2.9 Hz, 1H), 8.11 (d, J=9.0 Hz, 1H), 7.83 (d, J=2.4 Hz, 1H), 7.78 (dd, J=9.0, 2.9 Hz, 1H), 6.99 (dd, J=5.7, 2.4 Hz, 1H), 1.21 (s, 9H); MS (ESI) m/z: 393.2 (M+H+).

Workup

  1. temperatureheated at 75° C. for 1 h
  2. temperatureThe mixture was cooled to RT
  3. stirringstirred at RT for 1 h
  4. extractionextracted with DCM (2×)
  5. washthe combined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-7e27424989c044b68e86f52fa61d8dcf
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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