Trifluoroacetic acid → HCID 90403022, compound

HRID 1049362Notes

Reaction equation

HRID 1049362 reaction equation
[CH3:1][N:2]([C:10]1[N:15]=[CH:14][C:13]([C:16]2[CH:21]=[C:20]([O:22][C:23]3[CH:24]=[N:25][C:26]([NH:29][C:30]([NH:32][C:33](=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35])=[O:31])=[CH:27][CH:28]=3)[CH:19]=[CH:18][N:17]=2)=[CH:12][CH:11]=1)C(=O)OC(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:1][NH:2][C:10]1[N:15]=[CH:14][C:13]([C:16]2[CH:21]=[C:20]([O:22][C:23]3[CH:28]=[CH:27][C:26]([NH:29][C:30]([NH:32][C:33](=[O:38])[C:34]([CH3:36])([CH3:35])[CH3:37])=[O:31])=[N:25][CH:24]=3)[CH:19]=[CH:18][N:17]=2)=[CH:12][CH:11]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90403362HCID 90403362, compound

Product 1

HCID 90403022HCID 90403022, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl methyl(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)-[2,3′-bipyridin]-6′-yl)carbamate (0.1 g, 0.192 mmol) and TFA (0.148 mL, 1.921 mmol) in DCM (4 mL) was stirred at RT for 7 h, then concentrated to dryness. The residue was treated with satd. NaHCO3, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness. The material was treated with 30% EtOAc/Hex, sonicated and the resulting solid collected via filtration to afford N-((5-((6′-(methylamino)-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (61 mg, 76%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.21 (s, 1H), 10.42 (s, 1H), 8.69 (d, J=2.4 Hz, 1H), 8.44 (d, J=5.7 Hz, 1H), 8.27 (d, J=2.9 Hz, 1H), 8.09 (d, J=9.0 Hz, 1H), 8.02 (dd, J=8.8, 2.5 Hz, 1H), 7.75 (dd, J=9.0, 2.9 Hz, 1H), 7.39 (d, J=2.4 Hz, 1H), 6.83 (q, J=5.0 Hz, 1H), 6.73 (dd, J=5.7, 2.4 Hz, 1H), 6.48 (d, J=8.8 Hz, 1H), 2.80 (d, J=4.7 Hz, 3H), 1.21 (s, 9H); MS (ESI) m/z: 421.2 (M+H+).

Workup

  1. concentrationconcentrated to dryness
  2. additionThe residue was treated with satd
  3. extractionNaHCO3, extracted with EtOAc (2×)
  4. washthe combined organics were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to dryness
  7. additionThe material was treated with 30% EtOAc/Hex
  8. customsonicated
  9. filtrationthe resulting solid collected via filtration

Sources & evidence

ORD record
ord-57618a04f98c4c198c9c26209b10e1fd
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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