Pyridine → HCID 90403317, compound

HRID 1049352Notes

Reaction equation

HRID 1049352 reaction equation
[CH3:1][C:2]([CH3:7])([CH3:6])[C:3]([NH2:5])=[O:4].C(Cl)(=O)[C:9](Cl)=[O:10].[F:14][C:15]([F:37])([F:36])[C:16]1[N:21]=[CH:20][C:19]([C:22]2[CH:27]=[C:26]([O:28][C:29]3[CH:30]=[CH:31][C:32]([NH2:35])=[N:33][CH:34]=3)[CH:25]=[CH:24][N:23]=2)=[CH:18][CH:17]=1.N1C=CC=CC=1>ClCCCl.O1CCOCC1>[F:37][C:15]([F:14])([F:36])[C:16]1[N:21]=[CH:20][C:19]([C:22]2[CH:27]=[C:26]([O:28][C:29]3[CH:30]=[CH:31][C:32]([NH:35][C:9]([NH:5][C:3](=[O:4])[C:2]([CH3:7])([CH3:6])[CH3:1])=[O:10])=[N:33][CH:34]=3)[CH:25]=[CH:24][N:23]=2)=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 12957TrimethylacetamideHCID 65578Oxalyl chlorideHCID 90403388HCID 90403388, compound

Product 1

HCID 90403317HCID 90403317, compoundYield 65.3%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 2,2,2-trimethylacetamide (0.029 g, 0.284 mmol) in DCE (2 mL) was treated with oxalyl chloride (0.025 mL, 0.284 mmol), stirred at RT for 5 min, then heated at 80° C. for 0.5 h. The mixture was cooled to RT, added to a mixture of 5-((6′-(trifluoromethyl)-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-amine (0.063 g, 0.190 mmol) and pyridine (0.123 mL, 1.517 mmol) in dioxane (4 mL) and stirred at RT for 3 h. The mixture was treated with satd. NaHCO3, extracted with EtOAc (3×) and the combined organics were dried over Na2SO4 and concentrated to dryness. The material was treated with MeCN and the solid collected via filtration to afford N-((5-((6′-(trifluoromethyl)-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (57 mg, 65%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.24 (s, 1H); 10.47 (s, 1H); 9.41 (s, 1H); 8.67-8.66 (m, 2H), 8.31-8.30 (m, 1H), 8.11 (d, J=9.0 Hz, 1H); 8.00 (d, J=8.3 Hz, 1H); 7.84 (d, J=2.4 Hz, 1H); 7.79 (dd, J=9.0, 2.9 Hz, 1H); 7.01 (dd, J=5.7, 2.4 Hz, 1H); 1.21 (s, 9H); MS (ESI) m/z: 460.2 (M+H+).

Workup

  1. temperatureheated at 80° C. for 0.5 h
  2. temperatureThe mixture was cooled to RT
  3. stirringstirred at RT for 3 h
  4. additionThe mixture was treated with satd
  5. extractionNaHCO3, extracted with EtOAc (3×)
  6. dry with materialthe combined organics were dried over Na2SO4
  7. concentrationconcentrated to dryness
  8. additionThe material was treated with MeCN
  9. filtrationthe solid collected via filtration

Sources & evidence

ORD record
ord-ea85e677e81541f79ca052669f914a82
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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