Trimethylacetamide → N-(4-((2-methyl-6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)cyclopropanecarboxamide

HRID 626547Notes

Reaction equation

HRID 626547 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]([CH:32]3[CH2:34][CH2:33]3)=[O:31])[CH:24]=2)=[CH:17][CH:16]=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]([CH:32]3[CH2:34][CH2:33]3)=[O:31])[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

6

Reactant 3

HCID 12957TrimethylacetamideHCID 65578Oxalyl chlorideHCID 90409528N-(4-((6-amino-2-methylpyridin-3-yl)oxy)pyridin-2-yl)cyclopropanecarboxamide

Product 1

HCID 86272525N-(4-((2-methyl-6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)cyclopropanecarboxamideYield 39.4%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2,2,2-trimethylacetamide (0.046 g, 0.457 mmol) in DCE (2 mL) was treated with oxalyl chloride (0.040 mL, 0.457 mmol), stirred at RT for 0.5 h, then heated at 75° C. for 1 h. The mixture was cooled to RT, treated with a solution of Example A5 (0.10 g, 0.352 mmol) and TEA (0.098 mL, 0.703 mmol) in THF (2 mL) and stirred at RT for 1 h. The mixture was concentrated to dryness, the residue treated with EtOAc, the solid collected via filtration, washed with water and EtOAc and dried to afford N-(4-((2-methyl-6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)cyclopropanecarboxamide (57 mg, 39%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.16 (s, 1H), 10.86 (s, 1H), 10.41 (br s, 1H), 8.19 (d, J=5.6 Hz, 1H), 7.90 (m, 1H), 7.62 (d, J=8.9 Hz, 1H), 7.55 (m, 1H), 6.66 (m, 1H), 2.22 (s, 3H), 1.95 (m, 1H), 1.21 (s, 9H), 0.75 (d, J=5.9 Hz, 4H); MS (ESI) m/z: 412.2 (M+H+).

Workup

  1. temperatureheated at 75° C. for 1 h
  2. temperatureThe mixture was cooled to RT
  3. stirringstirred at RT for 1 h
  4. concentrationThe mixture was concentrated to dryness
  5. additionthe residue treated with EtOAc
  6. filtrationthe solid collected via filtration
  7. washwashed with water and EtOAc
  8. customdried

Sources & evidence

ORD record
ord-e8951fa3d9c94244913c83350275c793
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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