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

HRID 626541Notes

Reaction equation

HRID 626541 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]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH:23]=2)=[CH:17][CH:16]=1.N1C=CC=CC=1>ClCCCl>[C:3]([NH:5][C:9](=[O:10])[NH:14][C:15]1[N:20]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:32])([CH3:34])[CH3:33])[CH:23]=2)=[CH:17][CH:16]=1)(=[O:4])[C:2]([CH3:7])([CH3:6])[CH3:1]

Participants

6

Reactant 4

HCID 1049PyridineHCID 12957TrimethylacetamideHCID 65578Oxalyl chlorideHCID 131735223Tert-butyl (4-((6-aminopyridin-3-yl)oxy)pyridin-2-yl)carbamate

Product 1

HCID 131735224Tert-butyl (4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)carbamateYield 70.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 2,2,2-trimethylacetamide (0.750 g, 7.42 mmol) in DCE (10 mL) was treated with oxalyl chloride (0.600 mL, 7.09 mmol), stirred at RT for 10 min, then heated at 80° C. for 1 h. The mixture was cooled to RT, partially concentrated, then added drop-wise to a solution of tert-butyl (4-((6-aminopyridin-3-yl)oxy)pyridin-2-yl)carbamate (1.6 g, 5.29 mmol) in pyridine (0.60 mL, 7.44 mmol) and stirred at RT for 45 min. The mixture was concentrated to dryness, treated with MeCN, sonicated and the solids collected via filtration. The filtrate was concentrated to dryness, suspended in MeCN, sonicated, the resulting solid collected via filtration and combined with the above-isolated solid to afford tert-butyl (4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)carbamate (1.6 g, 70%). MS (ESI) m/z: 430.2 (M+H+).

Workup

  1. temperatureheated at 80° C. for 1 h
  2. temperatureThe mixture was cooled to RT
  3. concentrationpartially concentrated
  4. stirringstirred at RT for 45 min
  5. concentrationThe mixture was concentrated to dryness
  6. additiontreated with MeCN
  7. customsonicated
  8. filtrationthe solids collected via filtration
  9. concentrationThe filtrate was concentrated to dryness
  10. customsonicated
  11. filtrationthe resulting solid collected via filtration

Sources & evidence

ORD record
ord-e16fc15582f3428ab8c5cdf9d109aa8a
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

Loading…