Trimethylacetamide → N-((6-methyl-5-((2-propionamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide

HRID 626548Notes

Reaction equation

HRID 626548 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:33])[CH2:31][CH3:32])[CH:24]=2)=[CH:17][CH:16]=1>ClCCCl.C1COCC1>[CH3:21][C:19]1[N:20]=[C:15]([NH:14][C:9]([NH:5][C:3](=[O:4])[C:2]([CH3:7])([CH3:6])[CH3:1])=[O:10])[CH:16]=[CH:17][C:18]=1[O:22][C:23]1[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30](=[O:33])[CH2:31][CH3:32])[CH:24]=1

Participants

6

Reactant 3

HCID 12957TrimethylacetamideHCID 65578Oxalyl chlorideHCID 90409452N-(4-((6-amino-2-methylpyridin-3-yl)oxy)pyridin-2-yl)propionamide

Product 1

HCID 86275389N-((6-methyl-5-((2-propionamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamideYield 59.3%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2,2,2-trimethylacetamide (0.048 g, 0.477 mmol) in DCE (2 mL) was treated with oxalyl chloride (0.042 mL, 0.477 mmol), stirred at RT for 0.5 h, then heated at 75° C. for 1 h. The mixture was cooled to RT, added to a solution of Example A6 (0.10 g, 0.367 mmol) and TEA (0.1 mL, 0.744 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-((6-methyl-5-((2-propionamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (87 mg, 59%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.17 (s, 1H), 10.49 (s, 1H), 10.41 (br s, 1H), 8.17 (d, J=5.7 Hz, 1H), 7.90 (m, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.59 (d, J=2.4 Hz, 1H), 6.65 (dd, J=5.7, 2.4 Hz, 1H), 2.33 (q, J=7.5 Hz, 2H), 2.23 (s, 3H), 1.22 (s, 9H), 0.99 (t, J=7.5 Hz, 3H); MS (ESI) m/z: 400.2 (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-75d583189a8840bf9b2de59e766907d2
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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