Pyridine → Methyl 5-[[2-fluoro-5-(trifluoromethyl)benzoyl]amino]pyridine-2-carboxylate

HRID 515070Notes

Reaction equation

HRID 515070 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][C:3]=1[C:4](Cl)=[O:5].[NH2:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]([O:24][CH3:25])=[O:23])=[N:20][CH:21]=1.N1C=CC=CC=1>ClCCl>[F:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][C:3]=1[C:4]([NH:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]([O:24][CH3:25])=[O:23])=[N:20][CH:21]=1)=[O:5]

Participants

5

Reactant 3

HCID 1049PyridineHCID 27348802-Fluoro-5-(trifluoromethyl)benzoyl ChlorideHCID 12457877Methyl 5-aminopyridine-2-carboxylate

Product 1

HCID 90315083Methyl 5-[[2-fluoro-5-(trifluoromethyl)benzoyl]amino]pyridine-2-carboxylateYield 76.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 2-fluoro-5-(trifluoromethyl)benzoyl chloride (2.98 mL, 19.72 mmol) in dichloromethane (22.3 mL) was added drop-wise to a mixture of methyl 5-aminopyridine-2-carboxylate (3.0 g, 19.72 mmol), pyridine (4.80 mL, 59.16 mmol) and dichloromethane (89.4 mL) at 0° C. The mixture was removed from the ice bath after 1.5 hours and was stirred at room temperature for 0.5 hours. The mixture was poured into 1N HCl (50 mL) and dichloromethane (50 mL). The layers were separated and the organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The product was slurried in hexanes to remove impurities. The solid was isolated by filtration rinsing with hexanes to yield methyl 5-[[2-fluoro-5-(trifluoromethyl)benzoyl]amino]pyridine-2-carboxylate (5.16 g, 76%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.18 (s, 1H), 8.95 (d, J=2.5 Hz, 1H), 8.38 (dd, J=8.6, 2.5 Hz, 1H), 8.16 (dd, J=6.1, 2.4 Hz, 1H), 8.13 (d, J=8.6 Hz, 1H), 8.09-7.98 (m, 1H), 7.67 (t, J=9.2 Hz, 1H), 3.88 (s, 3H) ppm. ESI-MS m/z calc. 342.06, found 343.2 (M+1)+; Retention time: 1.54 minutes (3 minutes run).

Workup

  1. customThe mixture was removed from the ice bath after 1.5 hours
  2. additionThe mixture was poured into 1N HCl (50 mL) and dichloromethane (50 mL)
  3. customThe layers were separated
  4. dry with materialthe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto remove impurities
  8. customThe solid was isolated by filtration
  9. washrinsing with hexanes

Sources & evidence

ORD record
ord-ed82d03a8d0b4725978084df124642c9
Source dataset
uspto-grants-2015_08
Patent number
US09108903B2

Reaction notes

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