Pyridine → HCID 71575770, compound

HRID 1411146Notes

Reaction equation

HRID 1411146 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][N:7]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[C:6](=[O:17])[C:5]=1[C:18]([OH:20])=O)[CH3:2].O=S(Cl)Cl.[NH2:25][C:26]1[C:43]([F:44])=[CH:42][C:29]([O:30][C:31]2[CH:36]=[CH:35][N:34]=[C:33]([NH:37][C:38](=[O:41])[CH2:39][CH3:40])[CH:32]=2)=[C:28]([F:45])[CH:27]=1.N1C=CC=CC=1>C(Cl)Cl.O>[F:44][C:43]1[CH:42]=[C:29]([O:30][C:31]2[CH:36]=[CH:35][N:34]=[C:33]([NH:37][C:38](=[O:41])[CH2:39][CH3:40])[CH:32]=2)[C:28]([F:45])=[CH:27][C:26]=1[NH:25][C:18]([C:5]1[C:6](=[O:17])[N:7]([C:10]2[CH:11]=[CH:12][C:13]([F:16])=[CH:14][CH:15]=2)[CH:8]=[CH:9][C:4]=1[O:3][CH2:1][CH3:2])=[O:20]

Participants

7

Reactant 4

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 585350974-Ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acidHCID 86703359HCID 86703359, compound

Product 1

HCID 71575770HCID 71575770, compoundYield 82.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of Example B1, (5.2 g, 18.8 mmol) in SOCl2 (50 mL, 685 mmol) was heated at 60° C. for 2 h. The mixture was azeotroped with toluene and concentrated to dryness. The solid was dissolved in DCM (150 mL), cooled to 0° C. and treated with a solution of Example A3 (5 g, 17.1 mmol) and pyridine (0.14 mL, 1.74 mmol) in DCM (100 mL) over 20 min. The reaction mixture was stirred at 0° C. for 10 min and then warmed to RT for 2 h. Water (5 mL) was added and the mixture was concentrated in vacuo. The residue was triturated with water (200 mL) and the solids were collected by filtration, washed with water and dried under vacuum. The solids were dissolved in DCM (400 mL), washed with saturated NaHCO3 (2×100 mL) and brine (100 mL), dried over Na2SO4, and concentrated to dryness. The solids were triturated with hexanes/EtOAc (1:1), collected by filtration and dried under vacuum to give N-(2,5-difluoro-4-((2-propionamidopyridin-4-yl)oxy)phenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (7.5 g, 82.4% yield). 1H NMR (400 MHz, DMSO-d6): δ 11.22 (s, 1H), 10.52 (s, 1H), 8.33 (dd, J=12.6, 7.2 Hz, 1H), 8.18 (d, J=5.7 Hz, 1H), 7.92 (d, J=7.8 Hz, 1H), 7.68 (d, J=2.4 Hz, 1H), 7.50-7.48 (m, 3H), 7.36 (t, J=8.7 Hz, 2H), 6.72 (dd, J=5.7, 2.4 Hz, 1H), 6.55 (d, J=7.9 Hz, 1H), 4.28 (q, J=7.0 Hz, 2H), 2.33 (q, J=7.5 Hz, 2H), 1.34 (t, J=7.0 Hz, 3H), 0.99 (t, J=7.5 Hz, 3H); MS (ESI) m/z: 553.2 (M+H+).

Workup

  1. customThe mixture was azeotroped with toluene
  2. concentrationconcentrated to dryness
  3. dissolutionThe solid was dissolved in DCM (150 mL)
  4. temperaturewarmed to RT for 2 h
  5. concentrationthe mixture was concentrated in vacuo
  6. customThe residue was triturated with water (200 mL)
  7. filtrationthe solids were collected by filtration
  8. washwashed with water
  9. customdried under vacuum
  10. dissolutionThe solids were dissolved in DCM (400 mL)
  11. washwashed with saturated NaHCO3 (2×100 mL) and brine (100 mL)
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated to dryness
  14. customThe solids were triturated with hexanes/EtOAc (1:1)
  15. filtrationcollected by filtration
  16. customdried under vacuum

Sources & evidence

ORD record
ord-b6a519742bd442649b1ef70f0ebccb22
Source dataset
uspto-grants-2014_12
Patent number
US08921565B2

Reaction notes

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