Trimethylacetamide → HCID 86274907, compound

HRID 626588Notes

Reaction equation

HRID 626588 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]([C:28]([NH:30][CH:31]3[CH2:33][CH2:32]3)=[O:29])[CH:23]=2)=[CH:17][CH:16]=1.CCN(C(C)C)C(C)C>ClCCCl.O1CCOCC1.CCOC(C)=O>[CH:31]1([NH:30][C:28](=[O:29])[C:24]2[CH:23]=[C:22]([O:21][C:18]3[CH:19]=[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]=3)[CH:27]=[CH:26][N:25]=2)[CH2:32][CH2:33]1

Participants

8

Reactant 4

HCID 12957TrimethylacetamideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 90411099HCID 90411099, compound

Product 1

HCID 86274907HCID 86274907, compoundYield 67%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 2,2,2-trimethylacetamide (0.150 g, 1.480 mmol) in DCE (4 mL) was treated with oxalyl chloride (0.130 mL, 1.480 mmol), heated at 80° C. for 1 h, cooled to RT, added drop-wise to a solution of 4-((6-aminopyridin-3-yl)oxy)-N-cyclopropylpicolinamide (0.2 g, 0.740 mmol) and DIEA (0.646 mL, 3.70 mmol) in dioxane (4 mL) and stirred at RT for 20 h. The mixture was diluted with EtOAc, washed with satd. NaHCO3, water, then brine and the combined aqueous washes were back-extracted with EtOAc. The combined organics were dried over Na2SO4, concentrated to dryness and purified by silica gel chromatography (EtOAc/DCM) to afford N-cyclopropyl-4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)picolinamide (0.196 g, 67%). 1H NMR (400 MHz, DMSO-d6): δ 11.24 (s, 1H), 10.46 (s, 1H), 8.75 (d, J=5.1 Hz, 1H), 8.50 (d, J=5.6 Hz, 1H), 8.30 (d, J=2.9 Hz, 1H), 8.11 (d, J=9.0 Hz, 1H), 7.78 (dd, J=9.0, 2.9 Hz, 1H), 7.40 (d, J=2.6 Hz, 1H), 7.19 (dd, J=5.6, 2.6 Hz, 1H), 2.87-2.85 (m, 1H), 1.21 (s, 9H), 0.65 (d, J=8.0 Hz, 4H); MS (ESI) m/z: 398.2 (M+H+).

Workup

  1. temperaturecooled to RT
  2. washwashed with satd
  3. extractionNaHCO3, water, then brine and the combined aqueous washes were back-extracted with EtOAc
  4. dry with materialThe combined organics were dried over Na2SO4
  5. concentrationconcentrated to dryness
  6. custompurified by silica gel chromatography (EtOAc/DCM)

Sources & evidence

ORD record
ord-1fffef1dc21f40f9ab0f63e77650c682
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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