Triethylamine → 5-Fluoro-2-(4-fluorophenoxy)-N-[4-(2H-tetrazol-5-YL)benzyl]benzamide

HRID 1293229Notes

Reaction equation

HRID 1293229 reaction equation
[F:1][C:2]1[CH:3]=[CH: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.[N:20]1[NH:21][N:22]=[N:23][C:24]=1[C:25]1[CH:30]=[CH:29][C:28]([CH2:31][NH2:32])=[CH:27][CH:26]=1.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>ClCCl.CN(C)C=O>[F:1][C:2]1[CH:3]=[CH: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]([NH:32][CH2:31][C:28]1[CH:27]=[CH:26][C:25]([C:24]2[N:20]=[N:21][NH:22][N:23]=2)=[CH:30][CH:29]=1)=[O:9]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 23224690(4-(1H-1,2,3,4-tetrazol-5-yl)phenyl)methanamine hydrochlorideHCID 433133155-Fluoro-2-(4-fluorophenoxy)benzoic acid

Product 1

HCID 589053655-Fluoro-2-(4-fluorophenoxy)-N-[4-(2H-tetrazol-5-YL)benzyl]benzamideYield 73.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 5-fluoro-2-(4-fluorophenoxy)benzoic acid (120 mg, 0.48 mmol), 1-[4-(2H-tetrazol-5-yl)phenyl]methanamine hydrochloride (122 mg, 0.58 mmol), 1-hydroxy-1H-benztriazole monohydrate (110 mg, 0.72 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (138 mg, 0.72 mmol), and triethylamine (0.27 mL, 1.92 mmol) in dichloromethane (8 mL) and N,N-dimethylforamide (2 mL) was stirred at room temperature for 16 h. The mixture was diluted with dichloromethane (50 mL) and washed with 5% aqueous sodium dihydrogenphosphate solution (30 mL). The organic fraction 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/acetic acid (30:60:1) to afford 143 mg (73%) of the title compounds as white solids: 1H-NMR (DMSO-d6) δ 8.99 (1H, t, J=5.9 Hz), 7.91 (2H, d, J=8.2 Hz), 7.53–6.99 (8H, m), 4.50 (2H, d, J=5.9 Hz); MS (ESI) m/z 408 (M+H)+, 406 (M−H)−.

Workup

  1. washwashed with 5% aqueous sodium dihydrogenphosphate solution (30 mL)
  2. dry with materialThe organic fraction 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/acetic acid (30:60:1)

Sources & evidence

ORD record
ord-d58a8944d83f435aa4f6553dccd45b20
Source dataset
uspto-grants-2007_07
Patent number
US07238714B2

Reaction notes

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