Pyridine → N-(5-(tert-Butyl)-3,3-dimethyl-2-oxo-2,3-dihydrobenzofuran-6-yl)-4-oxo-1,4-dihydroquinoline-3-carboxamide

HRID 2205455Notes

Reaction equation

HRID 2205455 reaction equation
[NH2:1][C:2]1[C:13]([C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:12][C:5]2[C:6]([CH3:11])([CH3:10])[C:7](=[O:9])[O:8][C:4]=2[CH:3]=1.[CH3:18][CH:19]1[O:23][CH2:22][CH2:21][CH2:20]1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[N:42]1[CH:47]=[CH:46][CH:45]=C[CH:43]=1.[C:48](=O)([O-])[O:49]CC1C=C([N+]([O-])=O)C(C(C)(C)C)=CC=1Br>O>[C:14]([C:13]1[C:2]([NH:1][C:48]([C:18]2[C:19](=[O:23])[C:20]3[C:47](=[CH:46][CH:45]=[CH:22][CH:21]=3)[NH:42][CH:43]=2)=[O:49])=[CH:3][C:4]2[O:8][C:7](=[O:9])[C:6]([CH3:11])([CH3:10])[C:5]=2[CH:12]=1)([CH3:17])([CH3:16])[CH3:15]

Participants

7

Reactant 5

HCID 1049PyridineHCID 73012-Methyltetrahydrofuran2×HCID 111923Propylphosphonic anhydrideHCID 595441486-Amino-5-(tert-butyl)-3,3-dimethylbenzofuran-2(3H)-oneHCID 66670712(2-Bromo-4-tert-butyl-5-nitro-phenyl)methyl carbonate

Product 1

HCID 59544159N-(5-(tert-Butyl)-3,3-dimethyl-2-oxo-2,3-dihydrobenzofuran-6-yl)-4-oxo-1,4-dihydroquinoline-3-carboxamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A reaction vessel was charged with compound 26 (2.926 g, 15.43 mmol), Compound 20 (4.32 g, 18.52 mmol), 2-MeTHF (35.99 mL), and subsequently 50% T3P in 2-MeTHF (13.36 g, 21.00 mmol). Pyridine (2.441 g, 2.496 mL, 30.86 mmol) was added and the suspension heated at 47.5° C.±5° C. for 18 h. After completion, the reaction was cooled to ambient temperature and 2-MeTHF (36) and water (30 ml) were added. The layers were split and the organic layer was washed with 10 wt % citric acid solution (30 ml), water (30 ml) and twice with NaHCO3 (20 ml). The organic layer was washed with brine (50 ml), separated and the solvent removed in vacuo. The crude product was dissolved in MTBE (100 ml) and hexane (200 ml) was added as an anti-solvent. A solid precipitated and the resulting slurry was stirred for two hours. The solid was collected by suction filtration and the cake was washed with hexane. The resulting product was dried in a vacuum oven at 55° C. with nitrogen bleed to give the title compound as a beige solid. 1H-NMR (400 MHZ, DMSO-d6) δ 12.96 (d J 6.4 Hz, 1H); 12.1 (s, 1H); 8.9 (d, J=6.4 Hz, 1H); 8.33 (d, J 8 Hz, 1H); 7.84-7.75 (m, 2H); 7.55-7.48 (m, 3H); 1.47 (s, 6H); 1.45 (s, 9H).

Workup

  1. temperaturethe suspension heated at 47.5° C.±5° C. for 18 h
  2. customThe layers were split
  3. washthe organic layer was washed with 10 wt % citric acid solution (30 ml), water (30 ml) and twice with NaHCO3 (20 ml)
  4. washThe organic layer was washed with brine (50 ml)
  5. customseparated
  6. customthe solvent removed in vacuo
  7. dissolutionThe crude product was dissolved in MTBE (100 ml)
  8. additionhexane (200 ml) was added as an anti-solvent
  9. customA solid precipitated
  10. filtrationThe solid was collected by suction filtration
  11. washthe cake was washed with hexane
  12. customThe resulting product was dried in a vacuum oven at 55° C. with nitrogen

Sources & evidence

ORD record
ord-0fc4aff6ee3649fda4fc393bf9512a3d
Source dataset
uspto-grants-2016_06
Patent number
US09371287B2

Reaction notes

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