Pyridine → Tert-butyl (4-((2-methyl-6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)carbamate

HRID 626571Notes

Reaction equation

HRID 626571 reaction equation
[CH3:1][C:2]([CH3:7])([CH3:6])[C:3]([NH2:5])=[O:4].C(Cl)(=O)[C:9](Cl)=[O:10].[NH2:14][C:15]1[N:20]=[C:19]([CH3:21])[C:18]([O:22][C:23]2[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH:24]=2)=[CH:17][CH:16]=1.N1C=CC=CC=1>ClCCCl.C1COCC1>[CH3:21][C:19]1[C:18]([O:22][C:23]2[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:35])[CH3:34])[CH:24]=2)=[CH:17][CH:16]=[C:15]([NH:14][C:9]([NH:5][C:3](=[O:4])[C:2]([CH3:7])([CH3:6])[CH3:1])=[O:10])[N:20]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 12957TrimethylacetamideHCID 65578Oxalyl chlorideHCID 131735226Tert-butyl (4-((6-amino-2-methylpyridin-3-yl)oxy)pyridin-2-yl)carbamate

Product 1

HCID 131735227Tert-butyl (4-((2-methyl-6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)carbamateYield 65.5%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 2,2,2-trimethylacetamide (0.192 g, 1.897 mmol) in DCE (5 mL) was treated with oxalyl chloride (0.160 mL, 1.897 mmol), stirred at RT for 10 min, then heated at 80° C. for 1 h. The mixture was cooled to RT, added to a solution of tert-butyl (4-((6-amino-2-methylpyridin-3-yl)oxy)pyridin-2-yl)carbamate (0.400 g, 1.264 mmol) and pyridine (0.112 mL, 1.391 mmol) in THF (10 mL) and stirred at RT overnight. The mixture was concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford tert-butyl (4-((2-methyl-6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)carbamate (367 mg, 65%). MS (ESI) m/z: 444.3 (M+H+).

Workup

  1. temperatureheated at 80° C. for 1 h
  2. temperatureThe mixture was cooled to RT
  3. stirringstirred at RT overnight
  4. concentrationThe mixture was concentrated to dryness
  5. custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-708fe40f984645778baa064719cf2e23
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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