Diisopropylethylamine → 3-{[3-(3-Fluoro-pyridin-4-yl)-5-methyl isoxazole-4-carbonyl]-amino}cyclo-hexanecarboxylic acid ethy ester

HRID 1823294Notes

Reaction equation

HRID 1823294 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][CH:8]([NH:12][C:13]([O:15]C)=O)[CH2:7]1)=[O:5])[CH3:2].I[Si](C)(C)C.[F:22][C:23]1[CH:24]=[N:25][CH:26]=[CH:27][C:28]=1[C:29]1[C:33](C(O)=O)=[C:32]([CH3:37])[O:31][N:30]=1.Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>ClCCl.CN(C)C=O>[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][CH:8]([NH:12][C:13]([C:33]2[C:29]([C:28]3[CH:27]=[CH:26][N:25]=[CH:24][C:23]=3[F:22])=[N:30][O:31][C:32]=2[CH3:37])=[O:15])[CH2:7]1)=[O:5])[CH3:2]

Participants

9

Reactant 6

HCID 81531DiisopropylethylamineHCID 85247Trimethylsilyl iodideHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22170132HCID 22170132, compoundHCID 69652660HCID 69652660, compound

Product 1

HCID 696527063-{[3-(3-Fluoro-pyridin-4-yl)-5-methyl isoxazole-4-carbonyl]-amino}cyclo-hexanecarboxylic acid ethy esterYield 86%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Dissolve 3-methoxycarbonylamino-cyclohexanecarboxylic acid ethyl ester (513 mg, 2.24 mmol) in dry dichloromethane (10 mL). Add iodotrimethylsilane (0.48 mL, 3.4 mmol) and stir the resulting mixture for 2.5 h at ambient temperature. Quench with methanol (5 mL) and concentrate in vacuo. Concentrate the resulting residue twice from diethyl ether and use the crude amine salt directly without purification. Combine this amine salt with 3-(3-fluoro-pyridin-4-yl)-5-methyl-isoxazole-4-carboxylic acid (500 mg, 2.24 mmol),1-[3-(dimethylamino)-propyl]-3-ethylcarbodiimide hydrochloride (430 mg, 2.24 mmol), 1-hydroxy-7-azabenzo-triazole (305 mg, 2.24 mmol), and N,N-diisopropylethyl amine (2.0 mL, 11.5 mmol) in N,N-dimethylformamide (15 mL) and stir overnight at ambient temperature. Concentrate the mixture in vacuo and take up in water and extract with dichloromethane. Dry the combined extracts over sodium sulfate and concentrate in vacuo. Elute the resulting residue over silica gel using methanol/dichloromethane which to give 720 mg (86%) of the desired amide as a white solid. MS(ES): (M+1)+ 376.2, 377.3 m/z.

Workup

  1. customQuench with methanol (5 mL)
  2. concentrationconcentrate in vacuo
  3. concentrationConcentrate the resulting residue twice from diethyl ether
  4. customdirectly without purification
  5. concentrationConcentrate the mixture in vacuo
  6. extractionextract with dichloromethane
  7. dry with materialDry the combined extracts over sodium sulfate
  8. concentrationconcentrate in vacuo
  9. washElute the resulting residue over silica gel

Sources & evidence

ORD record
ord-81216655681141349592eb2e72a189fa
Source dataset
uspto-grants-2006_05
Patent number
US07037921B2

Reaction notes

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