Pyridine → HCID 90403189, compound

HRID 1049350Notes

Reaction equation

HRID 1049350 reaction equation
[CH3:1][C:2]([CH3:7])([CH3:6])[C:3]([NH2:5])=[O:4].C(Cl)(=O)[C:9](Cl)=[O:10].[O:14]1[C:18]([C:19]2[CH:24]=[C:23]([O:25][C:26]3[CH:27]=[CH:28][C:29]([NH2:32])=[N:30][CH:31]=3)[CH:22]=[CH:21][N:20]=2)=[CH:17][N:16]=[CH:15]1.N1C=CC=CC=1>ClCCCl.O1CCOCC1>[O:14]1[C:18]([C:19]2[CH:24]=[C:23]([O:25][C:26]3[CH:27]=[CH:28][C:29]([NH:32][C:9]([NH:5][C:3](=[O:4])[C:2]([CH3:7])([CH3:6])[CH3:1])=[O:10])=[N:30][CH:31]=3)[CH:22]=[CH:21][N:20]=2)=[CH:17][N:16]=[CH:15]1

Participants

7

Reactant 4

HCID 1049PyridineHCID 12957TrimethylacetamideHCID 65578Oxalyl chlorideHCID 90403203HCID 90403203, compound

Product 1

HCID 90403189HCID 90403189, compoundYield 40.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 2,2,2-trimethylacetamide (0.044 g, 0.431 mmol) in DCE (2 mL) was treated with oxalyl chloride (0.038 mL, 0.431 mmol), stirred at RT for 5 min, then heated at 80° C. for 0.5 h. The mixture was cooled to RT, added to a mixture of 5-((2-(oxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-amine (0.073 g, 0.287 mmol) and pyridine (0.186 mL, 2.297 mmol) in dioxane (4 mL) and stirred at RT for 3 h. The mixture was treated with satd. NaHCO3, extracted with EtOAc (3×) and the combined organics were dried over Na2SO4 and concentrated to dryness. The material was treated with MeCN and the solid collected via filtration to afford N-((5-((2-(oxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (44 mg, 40%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.24 (s, 1H), 10.45 (s, 1H), 8.52 (d, J=5.7 Hz, 1H), 8.49 (s, 1H), 8.31 (d, J=2.9 Hz, 1H), 8.11 (d, J=9.0 Hz, 1H), 7.81-7.77 (m, 2H), 7.27 (d, J=2.5 Hz, 1H), 6.95 (dd, J=5.7, 2.5 Hz, 1H), 1.21 (s, 9H); MS (ESI) m/z: 382.2 (M+H+).

Workup

  1. temperatureheated at 80° C. for 0.5 h
  2. temperatureThe mixture was cooled to RT
  3. stirringstirred at RT for 3 h
  4. additionThe mixture was treated with satd
  5. extractionNaHCO3, extracted with EtOAc (3×)
  6. dry with materialthe combined organics were dried over Na2SO4
  7. concentrationconcentrated to dryness
  8. additionThe material was treated with MeCN
  9. filtrationthe solid collected via filtration

Sources & evidence

ORD record
ord-ecbc7028e7424f308808f79b9a118332
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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