Triethylamine → N-(1-Adamantyl)-5-(2-[4-morpholinyl]ethoxy)-1-(4-isopropylphenyl)pyrazole-4-carboxamide

HRID 617228

Reaction equation

HRID 617228 reaction equation
[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:14]([O:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[C:13]([C:24](O)=[O:25])[CH:12]=[N:11]2)=[CH:6][CH:5]=1)([CH3:3])[CH3:2].ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.C(N(CC)CC)C.Cl.[C:56]12([NH2:66])[CH2:65][CH:60]3[CH2:61][CH:62]([CH2:64][CH:58]([CH2:59]3)[CH2:57]1)[CH2:63]2.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C(Cl)(Cl)Cl.C(OCC)(=O)C>[C:56]12([NH:66][C:24]([C:13]3[CH:12]=[N:11][N:10]([C:7]4[CH:8]=[CH:9][C:4]([CH:1]([CH3:2])[CH3:3])=[CH:5][CH:6]=4)[C:14]=3[O:15][CH2:16][CH2:17][N:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)=[O:25])[CH2:63][CH:62]3[CH2:61][CH:60]([CH2:59][CH:58]([CH2:64]3)[CH2:57]1)[CH2:65]2

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 64150Amantadine HydrochlorideHCID 757711-HydroxybenzotriazoleHCID 179194001-(4-Isopropylphenyl)-5-(2-[4-morpholinyl]ethoxy)pyrazole-4-carboxylic acid

Product 1

HCID 9826992N-(1-Adamantyl)-5-(2-[4-morpholinyl]ethoxy)-1-(4-isopropylphenyl)pyrazole-4-carboxamideYield 14.4%

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 1-(4-isopropylphenyl)-5-(2-[4-morpholinyl]ethoxy)pyrazole-4-carboxylic acid (43 mg, 0.12 mmol) in dimethylformamide (1 mL) under an argon atmosphere, was added 1-hydroxybenzotriazole (16 mg, 0.12 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (25 mg, 0.13 mmol), triethylamine (60 uL, 0.43 mmol) and 1-adamantanamine hydrochloride (25 mg, 0.13 mmol). The reaction mixture was stirred for 24 h at room temperature, heated to 70° C. for 2 h, and stirred for another 96 h at room temperature. The resulting mixture was treated with aqueous sodium carbonate, extracted with ethyl acetate, washed with water four times and dried over Na2SO4. The extract was concentrated in vacuo. This coupling was repeated on the same scale and the combined residue was purified by chromatography twice over silica gel eluting the first column with 2 to 3% methanol in chloroform, and the second with 30 to 40% ethyl acetate in chloroform to afford the title compound (7% yield, 8.5 mg) as a yellow powder, mp 132-134° C. MS (ES) m/e 493.4 [M+H]+.

Workup

  1. temperatureheated to 70° C. for 2 h
  2. stirringstirred for another 96 h at room temperature
  3. extractionextracted with ethyl acetate
  4. washwashed with water four times
  5. dry with materialdried over Na2SO4
  6. concentrationThe extract was concentrated in vacuo
  7. customthe combined residue was purified by chromatography twice over silica gel eluting the first column with 2 to 3% methanol in chloroform

Sources & evidence

ORD record
ord-ef57082c3f34480bb8176acc12378372
Source dataset
uspto-grants-1999_09
Patent number
US05948777

Linked notes

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