Triethylamine → HCID 59153165, compound

HRID 2355298Notes

Reaction equation

HRID 2355298 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:28]=[CH:27][C:7]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16](=[O:21])[CH2:17][CH:18]([CH3:20])[CH3:19])=[C:12]([OH:22])[C:11]=2[C:23]([F:26])([F:25])[F:24])=[CH:6][CH:5]=1.[CH3:29][N:30]1[CH:34]=[C:33]([C:35](O)=[O:36])[N:32]=[CH:31]1.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC>O1CCCC1.O>[OH:22][C:12]1[C:11]([C:23]([F:24])([F:25])[F:26])=[C:10]([CH:15]=[CH:14][C:13]=1[C:16](=[O:21])[CH2:17][CH:18]([CH3:20])[CH3:19])[O:9][CH2:8][C:7]1[CH:6]=[CH:5][C:4]([CH2:3][NH:2][C:35]([C:33]2[N:32]=[CH:31][N:30]([CH3:29])[CH:34]=2)=[O:36])=[CH:28][CH:27]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 5415091-methyl-1H-imidazole-4-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67177680HCID 67177680, compound

Product 1

HCID 59153165HCID 59153165, compoundYield 53.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Mix 1-[4-(4-aminomethyl-benzyloxy)-2-hydroxy-3-trifluoromethyl-phenyl]-3-methyl-butan-1-one hydrochloride (120 mg, 287.2 μmol), 1-methyl-1-H-imidazole-4-carboxylic acid (43.5 mg, 344.6 μmol), 1-hydroxybenzotriazole hydrate (52.8 mg, 344.6 μmol) in anhydrous tetrahydrofuran (4.5 mL). Add triethylamine (72.7 mg, 718 μmol, 100 μL) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (66.1 mg, 344.6 μmol) to the mixture. Stir the reaction mixture at room temperature overnight. Dilute the reaction mixture with water. Extract the mixture with ethyl acetate (3×). Combine the organic layers, wash with brine, dry over sodium sulfate, and concentrate under reduced pressure. Purify the crude residue by flash chromatography (silica gel) eluting with 5% methanol/ethyl acetate followed by reverse phase chromatography using 90/10 to 20/80 (water/0.1% trifluoroacetic acid)/acetonitrile to provide the product as a white solid (75 mg, 153 μmol, 53.4% yield). MS (m/z): 490 (M+1).

Workup

  1. extractionExtract the mixture with ethyl acetate (3×)
  2. washCombine the organic layers, wash with brine
  3. dry with materialdry over sodium sulfate
  4. concentrationconcentrate under reduced pressure
  5. customPurify the crude residue by flash chromatography (silica gel)
  6. washeluting with 5% methanol/ethyl acetate

Sources & evidence

ORD record
ord-2ef13e3830df41fea16e3aa92630bece
Source dataset
uspto-grants-2010_07
Patent number
US07754742B2

Reaction notes

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