Triethylamine → n-(3-Tert-butyl-1-((tetrahydro-2h-pyran-2-yl)methyl)-1h-pyrazol-5-yl)-2-methoxy-5-(trifluoromethyl)benzamide

HRID 717251

Reaction equation

HRID 717251 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH2:10])[N:7]([CH2:11][CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:18][O:19][C:20]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][C:21]=1[C:22](O)=[O:23].ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.Cl.C(N(CC)CC)C>O1CCCC1>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:22](=[O:23])[C:21]2[CH:25]=[C:26]([C:29]([F:31])([F:32])[F:30])[CH:27]=[CH:28][C:20]=2[O:19][CH3:18])[N:7]([CH2:11][CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 135859092-Methoxy-5-(trifluoromethyl)benzoic acidHCID 675445333-Tert-butyl-1-((tetrahydro-2h-pyran-2-yl)methyl)-1h-pyrazol-5-amine

Product 1

HCID 66698366n-(3-Tert-butyl-1-((tetrahydro-2h-pyran-2-yl)methyl)-1h-pyrazol-5-yl)-2-methoxy-5-(trifluoromethyl)benzamideYield 14.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of Example 63C (0.73 g, 3.1 mmol) in tetrahydrofuran (20 mL) were added 2-methoxy-5-(trifluoromethyl)benzoic acid (0.68 g, 3.1 mmol, JRD Fluorochemicals), 1-hydroxybenzotriazole (0.47 g, 3.1 mmol, Aldrich), N-(3-dimethylaminopropyl)-N-ethylcarbodimide hydrochloride (0.59 g, 3.1 mmol) and triethylamine (1.3 mL, 9.2 mmol). After stirring at 60° C. for 16 h, the reaction mixture was cooled and quenched with saturated NaHCO3 (20 mL). The aqueous layer was extracted with ethyl acetate (3×20 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-50% ethyl acetate in hexanes) to provide 0.2 g of the title compound. MS (ESI+) m/z 440 (M+H)+.

Workup

  1. temperaturethe reaction mixture was cooled
  2. customquenched with saturated NaHCO3 (20 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×20 mL)
  4. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-9d742e8729d247f3812f57f724b2ed27
Source dataset
uspto-grants-2015_11
Patent number
US09193713B2

Linked notes

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