1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-[4-(4-Ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoyl]piperazine-2,6-dione

HRID 389988Notes

Reaction equation

HRID 389988 reaction equation
C(N(CC)C(C)C)(C)C.Cl.[NH:11]1[C:16](=[O:17])[CH2:15][NH:14][CH2:13][C:12]1=[O:18].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[CH2:40]([C:42]1[C:58]([F:59])=[CH:57][C:45]([O:46][C:47]2[CH:55]=[CH:54][C:50]([C:51](O)=[O:52])=[CH:49][C:48]=2[F:56])=[C:44]([O:60][CH3:61])[CH:43]=1)[CH3:41].[Cl-].[NH4+]>ClCCl>[CH2:40]([C:42]1[C:58]([F:59])=[CH:57][C:45]([O:46][C:47]2[CH:55]=[CH:54][C:50]([C:51]([N:14]3[CH2:15][C:16](=[O:17])[NH:11][C:12](=[O:18])[CH2:13]3)=[O:52])=[CH:49][C:48]=2[F:56])=[C:44]([O:60][CH3:61])[CH:43]=1)[CH3:41]

Participants

8

Reactant 6

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 12476478Piperazine-2,6-dione hydrochlorideHCID 671160464-(4-Ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoic acid

Product 1

HCID 671160884-[4-(4-Ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoyl]piperazine-2,6-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N-Diisopropylethylamine (0.29 mL, 1.7 mmol), piperazine-2,6-dione hydrochloride (88 mg, 0.58 mmol), EDCI (112 mg, 0.58 mmol) and HOBt (79 mg, 0.58 mmol) were successively added to a solution of 4-(4-ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoic acid (which may be prepared in accordance with the experimental described in Example 4, step 4; 150 mg, 0.48 mmol) in dichloromethane (1.6 mL). The reaction mixture was stirred at room temperature overnight then diluted by addition of dichloromethane (20 mL) and a saturated solution of ammonium chloride (20 mL). After separation, the aqueous layer was extracted with dichloromethane (2×20 mL). The combined organic phases were washed with a saturated solution of sodium hydrogen carbonate (20 mL), dried over sodium sulfate, filtered and concentrated under vacuum. The residue was purified by chromatography on silica gel, using dichloromethane/methanol (95:5 to 90:10) as eluent. The title product was obtained as a beige solid (130 mg, 66%).

Workup

  1. custommay be prepared in accordance with the
  2. customAfter separation
  3. extractionthe aqueous layer was extracted with dichloromethane (2×20 mL)
  4. washThe combined organic phases were washed with a saturated solution of sodium hydrogen carbonate (20 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-4477632d22db455b89031aeb19ce8f64
Source dataset
uspto-grants-2013_02
Patent number
US08383621B2

Reaction notes

Loading…