Triethylamine → N-(4-((2-chloropyridin-4-yl)oxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

HRID 1472616Notes

Reaction equation

HRID 1472616 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:15]([F:16])=[CH:14][C:12]([NH2:13])=[C:11]([F:17])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.CCN(CC)CC.[F:25][C:26]1[CH:31]=[CH:30][C:29]([N:32]2[CH:37]=[CH:36][CH:35]=[C:34]([C:38](Cl)=[O:39])[C:33]2=[O:41])=[CH:28][CH:27]=1>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:15]([F:16])=[CH:14][C:12]([NH:13][C:38]([C:34]3[C:33](=[O:41])[N:32]([C:29]4[CH:28]=[CH:27][C:26]([F:25])=[CH:31][CH:30]=4)[CH:37]=[CH:36][CH:35]=3)=[O:39])=[C:11]([F:17])[CH:10]=2)[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 596809561-(4-Fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carbonyl chlorideHCID 78358387Benzenamine, 4-[(2-chloro-4-pyridinyl)oxy]-2,5-difluoro-

Product 1

HCID 117700476N-(4-((2-chloropyridin-4-yl)oxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamideYield 38.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of Example A1 (0.147 g, 0.572 mmol) in THF (1 mL) was treated with Et3N (0.120 mL, 0.858 mmol) and a suspension of Example A3 (0.216 g, 0.858 mmol) in THF (2 mL). The mixture was layered with argon and stirred at RT overnight. The mixture was cooled to RT, the solid removed via filtration, rinsed with THF and the filtrate concentrated to dryness. The residue was triturated with MeCN, sonicated and the resulting solid collected via filtration and dried to afford N-(4-((2-chloropyridin-4-yl)oxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (104 mg, 38%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 12.51 (s, 1H), 8.71-8.61 (m, 2H), 8.38 (d, J=5.8 Hz, 1H), 8.23 (dd, J=6.6, 2.2 Hz, 1H), 7.69 (m, 3H), 7.49 (m, 2H), 7.25 (d, J=2.3 Hz, 1H), 7.13 (dd, J=5.8, 2.3 Hz, 1H), 6.82 (m, 1H).

Workup

  1. temperatureThe mixture was cooled to RT
  2. customthe solid removed via filtration
  3. washrinsed with THF
  4. concentrationthe filtrate concentrated to dryness
  5. customThe residue was triturated with MeCN
  6. customsonicated
  7. filtrationthe resulting solid collected via filtration
  8. customdried

Sources & evidence

ORD record
ord-da9e8f4d402e45e2bfde201ad0058eaf
Source dataset
uspto-grants-2015_04
Patent number
US09012635B2

Reaction notes

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