Water → HCID 86270080, compound

HRID 1049375Notes

Reaction equation

HRID 1049375 reaction equation
[CH3:1][C:2]([CH3:7])([CH3:6])[C:3]([NH2:5])=[O:4].C(Cl)(=O)[C:9](Cl)=[O:10].[CH3:14][C:15]1[N:20]=[C:19]([NH2:21])[CH:18]=[CH:17][C:16]=1[O:22][C:23]1[CH:28]=[CH:27][N:26]=[C:25]([C:29]2[S:33][CH:32]=[N:31][CH:30]=2)[CH:24]=1.O>ClCCCl.C1COCC1>[CH3:14][C:15]1[N:20]=[C:19]([NH:21][C:9]([NH:5][C:3](=[O:4])[C:2]([CH3:7])([CH3:6])[CH3:1])=[O:10])[CH:18]=[CH:17][C:16]=1[O:22][C:23]1[CH:28]=[CH:27][N:26]=[C:25]([C:29]2[S:33][CH:32]=[N:31][CH:30]=2)[CH:24]=1

Participants

7

Reactant 4

HCID 962WaterHCID 12957TrimethylacetamideHCID 65578Oxalyl chlorideHCID 90403023HCID 90403023, compound

Product 1

HCID 86270080HCID 86270080, compoundYield 84.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2,2,2-trimethylacetamide (0.071 g, 0.703 mmol) in DCE (3 mL) was treated with oxalyl chloride (0.062 mL, 0.703 mmol), stirred at RT for 1 h, then heated at 75° C. for 2 h. The mixture was cooled to RT, treated with a solution of 6-methyl-5-((2-(thiazol-5-yl)pyridin-4-yl)oxy)pyridin-2-amine (0.1 g, 0.352 mmol) and TEA (0.146 mL, 1.055 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/EtOAc) to afford N-((6-methyl-5-((2-(thiazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (122 mg, 84%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.17 (s, 1H), 10.45 (br s, 1H), 9.13 (s, 1H), 8.61 (s, 1H), 8.42 (d, J=5.8 Hz, 1H), 7.92 (s, 1H), 7.66-7.65 (m, 2H), 6.75 (dd, J=5.8, 2.4 Hz, 1H), 2.27 (s, 3H), 1.21 (s, 9H); MS (ESI) m/z: 412.2 (M+H+).

Workup

  1. temperatureheated at 75° C. for 2 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/EtOAc)

Sources & evidence

ORD record
ord-6549ca91a347441699b25f0619bec7da
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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