Water → HCID 90403487, compound

HRID 1049372Notes

Reaction equation

HRID 1049372 reaction equation
[CH3:1][C:2]([CH3:7])([CH3:6])[C:3]([NH2:5])=[O:4].C(Cl)(=O)[C:9](Cl)=[O:10].[S: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.O>ClCCCl.C1COCC1>[S: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 962WaterHCID 12957TrimethylacetamideHCID 65578Oxalyl chlorideHCID 90403026HCID 90403026, compound

Product 1

HCID 90403487HCID 90403487, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2,2,2-trimethylacetamide (0.090 g, 0.888 mmol) in DCE (3 mL) was treated with oxalyl chloride (0.078 mL, 0.888 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 5-((2-(thiazol-5-yl)pyridin-4-yl)oxy)pyridin-2-amine (0.12 g, 0.444 mmol) and TEA (0.186 mL, 1.332 mmol) in THF (5 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-((5-((2-(thiazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (67 mg, 38%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.23 (s, 1H), 10.44 (s, 1H), 9.13 (s, 1H), 8.61 (s, 1H), 8.44 (d, J=5.8 Hz, 1H), 8.29 (d, J=2.9 Hz, 1H), 8.10 (d, J=9.0 Hz, 1H), 7.77 (dd, J=9.0, 2.9 Hz, 1H), 7.70 (d, J=2.4 Hz, 1H), 6.86 (dd, J=5.8, 2.4 Hz, 1H), 1.21 (s, 9H); MS (ESI) m/z: 398.1 (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-40fffa7dfa0b4dcf8d501a9822eb40e7
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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