Tetrahydrofuran → 5-chloro-1-phenyl-1H-pyrazole-4-carboxylic acid adamantan-2-ylamide

HRID 1710339Notes

Reaction equation

HRID 1710339 reaction equation
[Cl:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:13]([OH:15])=O.[CH:16](N(C(C)C)CC)([CH3:18])[CH3:17].Cl.CN(C)[CH2:28][CH2:29][CH2:30][N:31]=C=NCC.O1[CH2:41][CH2:40][CH2:39][CH2:38]1>ClCCl>[CH:29]12[CH2:28][CH:40]3[CH2:41][CH:16]([CH2:18][CH:38]([CH2:39]3)[CH:30]1[NH:31][C:13]([C:3]1[CH:4]=[N:5][N:6]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:2]=1[Cl:1])=[O:15])[CH2:17]2

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 71471255-chloro-1-phenyl-1H-pyrazole-4-carboxylic acid2×

Product 1

HCID 575502625-chloro-1-phenyl-1H-pyrazole-4-carboxylic acid adamantan-2-ylamideYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-chloro-1-phenyl-1H-pyrazole-4-carboxylic acid (Intermediate 2; 5.8 g, 26.1 mmol) in tetrahydrofuran (70 mL) was added 2-adamantamine hydrochloride (available from Aldrich; 6.0 g, 32.0 mmol, 1.2 equivalents) and diisopropylethylamine (5.7 mL, 32.7 mmol, 1.2 equivalents). 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC; 7.5 g, 39.1 mmol, 1.5 equivalents) was added portionwise with stirring. Following complete addition of the EDC, the reaction mixture was stirred at 70° C. for ˜2 hours (reaction progress monitored by TLC and LCMS). The reaction mixture was dissolved in dichloromethane (300 mL), washed with 1N hydrochloric acid (2×200 mL), and brine (200 mL), then dried over magnesium sulfate, filtered, evaporated, and purified by column chromatography (eluting with 20% ethyl acetate in heptane) to give 5-chloro-1-phenyl-1H-pyrazole-4-carboxylic acid adamantan-2-ylamide (4.2 g, 11.8 mmol, 45%), which HPLC analysis indicated was 90% pure. This material was used directly in the next step without further purification.

Workup

  1. stirringthe reaction mixture was stirred at 70° C. for ˜2 hours
  2. custom(reaction progress monitored by TLC and LCMS)
  3. washwashed with 1N hydrochloric acid (2×200 mL), and brine (200 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. custompurified by column chromatography (eluting with 20% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-3743a9b017c04d938a5093e059a61a77
Source dataset
uspto-grants-2010_09
Patent number
US07790711B2

Reaction notes

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