Triethylamine → Methyl 4-[({[5-chloro-2-(4-fluorophenoxy)pyridin-3-yl]carbonyl}amino)methyl]benzoate

HRID 1293176Notes

Reaction equation

HRID 1293176 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([O:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[C:6]([CH:10]=1)[C:7]([OH:9])=O.Cl.[NH2:20][CH2:21][C:22]1[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][CH:23]=1.C(N(CC)CC)C.F[B-](F)(F)F.BrC1C=CC=C[N+]=1CC>ClCCl>[Cl:1][C:2]1[CH:10]=[C:6]([C:7]([NH:20][CH2:21][C:22]2[CH:23]=[CH:24][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:30][CH:31]=2)=[O:9])[C:5]([O:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[N:4][CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2729253Methyl 4-(aminomethyl)benzoate hydrochlorideHCID 27363002-Bromo-1-ethylpyridinium tetrafluoroborateHCID 178328455-Chloro-2-(4-fluorophenoxy)nicotinic acid

Product 1

HCID 57572311Methyl 4-[({[5-chloro-2-(4-fluorophenoxy)pyridin-3-yl]carbonyl}amino)methyl]benzoateYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 5-chloro-2-(4-fluorophenoxy)nicotinic acid (150 mg, 0.56 mmol), methyl 4-(aminomethyl)benzoate hydrochloride (136 mg, 0.67 mmol), and triethylamine (0.31 mL, 2.24 mmol) in dichloromethane (8 mL) was added 2-bromo-1-ethylpyridinium tetrafluoroborate (230 mg, 0.84 mmol) at 0° C. The resulting mixture was warmed to room temperature and stirred for 16 h. The mixture was diluted with dichloromethane (50 mL) and washed with 1N hydrochloric acid (30 mL), saturated aqueous sodium hydrogen carbonate solution (30 mL), and brine (30 mL). The organic layer was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by flush column chromatography on silica gel eluting with hexane/ethyl acetate (2:1) to afford 155 mg (67%) of the title compounds as white solids: 1H-NMR (CDCl3) δ 8.59 (1H, dd, J=2.6, 0.9 Hz), 8.26–8.17 (1H, m), 8.13 (1H, dd, J=2.8, 0.9 Hz), 8.00 (2H, d, J=8.1 Hz), 7.41 (2H, d, J=8.1 Hz), 7.15–7.07 (4H, m), 4.76 (2H, d, J=5.9 Hz), 3.90 (3H, s); MS (ESI) m/z 415 (M+H)+, 413 (M−H)−.

Workup

  1. washwashed with 1N hydrochloric acid (30 mL), saturated aqueous sodium hydrogen carbonate solution (30 mL), and brine (30 mL)
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified
  5. customby flush column chromatography on silica gel eluting with hexane/ethyl acetate (2:1)

Sources & evidence

ORD record
ord-d9176198463e4f1dbfab689980615444
Source dataset
uspto-grants-2007_07
Patent number
US07238714B2

Reaction notes

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