Pyridine → N-(2-((3,5-dimethylisoxazol-4-yl)methyl)-2H-tetrazol-5-yl)-3-methoxybenzamide

HRID 1686318Notes

Reaction equation

HRID 1686318 reaction equation
[CH3:1][C:2]1[C:6]([CH2:7][N:8]2[N:12]=[N:11][C:10]([NH2:13])=[N:9]2)=[C:5]([CH3:14])[O:4][N:3]=1.[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=1)[C:20](Cl)=[O:21].N1C=CC=CC=1>C(#N)C.ClCCl>[CH3:1][C:2]1[C:6]([CH2:7][N:8]2[N:12]=[N:11][C:10]([NH:13][C:20](=[O:21])[C:19]3[CH:23]=[CH:24][CH:25]=[C:17]([O:16][CH3:15])[CH:18]=3)=[N:9]2)=[C:5]([CH3:14])[O:4][N:3]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 74374m-Anisoyl chlorideHCID 574224592-((3,5-dimethylisoxazol-4-yl)methyl)-2H-tetrazol-5-amine

Product 1

HCID 57422458N-(2-((3,5-dimethylisoxazol-4-yl)methyl)-2H-tetrazol-5-yl)-3-methoxybenzamideYield 35%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

2-((3,5-dimethylisoxazol-4-yl)methyl)-2H-tetrazol-5-amine (Example 10-39a) (102 mg, 0.528 mmol), 3-methoxybenzoyl chloride (0.065 mL, 0.528 mmol) and pyridine (0.043 mL, 0.528 mmol) in acetonitrile (3 mL) were stirred at 100° C. for one hour. The reaction was diluted with dichloromethane (30 mL) and washed with brine (30 mL). The organics were dried over sodium sulfate, concentrated and purified by reverse phase HPLC (Solvent system: acetonitrile/water 10% to 100% gradient), 25 minute run) affording N-(2-((3,5-dimethylisoxazol-4-yl)methyl)-2H-tetrazol-5-yl)-3-methoxybenzamide as a white crystalline solid (60 mg, 35% yield) MS M+H calculated 329.1. found 329. 1H NMR (400 MHz, DMSO-d6): δ 2.02 (s, 3H), 2.46 (s, 3H), 3.81 (s, 3H), 5.78 (s, 2H), 7.16 (m, 1H), 7.42 (t, J=8 Hz, 2H), 7.54 (m, 1H), 11.3 (s, 1H). The compound had an IC50 on hT2R8 bitter receptor of 1.87 μM.

Workup

  1. washwashed with brine (30 mL)
  2. dry with materialThe organics were dried over sodium sulfate
  3. concentrationconcentrated
  4. custompurified by reverse phase HPLC (Solvent system: acetonitrile/water 10% to 100% gradient), 25 minute

Sources & evidence

ORD record
ord-6f34410c32e64dba9af29c44eac00371
Source dataset
uspto-grants-2012_04
Patent number
US08148544B2

Reaction notes

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