3-(Trifluoromethyl)aniline → HCID 21110127, compound

HRID 1766360Notes

Reaction equation

HRID 1766360 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8](=[O:13])[CH2:9][C:10]([O-:12])=O)[CH2:4][CH2:3]1.[Li+].[F:15][C:16]([F:25])([F:24])[C:17]1[CH:18]=[C:19]([CH:21]=[CH:22][CH:23]=1)[NH2:20].C(N(C(C)C)C(C)C)C.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O>[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([C:8](=[O:13])[CH2:9][C:10]([NH:20][C:19]2[CH:21]=[CH:22][CH:23]=[C:17]([C:16]([F:15])([F:24])[F:25])[CH:18]=2)=[O:12])[CH2:6][CH2:7]1

Participants

7

Reactant 5

HCID 73753-(Trifluoromethyl)anilineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 23693663HCID 23693663, compound

Product 1

HCID 21110127HCID 21110127, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of Example 47A (700 mg, 3.64 mmol), 3-trifluoromethylaniline (646 mg, 4.01 mmol), ethyldiisopropylamine (1036 mg, 8.01 mmol), 1-hydroxy-1H-benzotriazol hydrate (591 mg, 4.37 mmol), and 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide hydrochloride (908 mg, 4.74 mmol) in dimethyl formamide (30 ml) is stirred at room temperature overnight (18 h). The solvent is removed in vacuo and the residue is dissolved in 300 ml water/ethyl acetate. The phases are separated and the aqueous phase is extracted three times with ethyl acetate. The organic layers are combined, washed with brine, and the solvent is removed in vacuo. The crude product is purified by flash chromatography over silica gel with cyclohexane/ethyl acetate as eluent. The resulting product is further purified by preparative HPLC (acetonitrile/water 1:9 to 9:1 gradient) to afford a pale yellow solid.

Workup

  1. customThe solvent is removed in vacuo
  2. dissolutionthe residue is dissolved in 300 ml water/ethyl acetate
  3. customThe phases are separated
  4. extractionthe aqueous phase is extracted three times with ethyl acetate
  5. washwashed with brine
  6. customthe solvent is removed in vacuo
  7. customThe crude product is purified by flash chromatography over silica gel with cyclohexane/ethyl acetate as eluent
  8. customThe resulting product is further purified by preparative HPLC (acetonitrile/water 1:9 to 9:1 gradient)
  9. customto afford a pale yellow solid

Sources & evidence

ORD record
ord-ac0be46d5da0416480b6d00b58db79b3
Source dataset
uspto-grants-2007_06
Patent number
US07230017B2

Reaction notes

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