Triethylamine → thiophene-3-carboxylic acid N'-[2-(5-fluoro-2'-ethyl-biphenyl-2-yloxy)-acetyl]-N'-isopropyl hydrazide

HRID 2250935Notes

Reaction equation

HRID 2250935 reaction equation
[CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[O:16][CH2:17][C:18]([OH:20])=O)[CH3:2].[CH:21]([NH:24][NH:25][C:26]([C:28]1[CH:32]=[CH:31][S:30][CH:29]=1)=[O:27])([CH3:23])[CH3:22].C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C>[F:15][C:13]1[CH:12]=[CH:11][C:10]([O:16][CH2:17][C:18]([N:24]([CH:21]([CH3:23])[CH3:22])[NH:25][C:26]([C:28]2[CH:32]=[CH:31][S:30][CH:29]=2)=[O:27])=[O:20])=[C:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[CH2:1][CH3:2])[CH:14]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 58689898(2'-Ethyl-5-fluoro-biphenyl-2-yloxy)-acetic acidHCID 59642162thiophene-3-carboxylic acid N'-isopropyl-hydrazide

Product 1

HCID 11597369thiophene-3-carboxylic acid N'-[2-(5-fluoro-2'-ethyl-biphenyl-2-yloxy)-acetyl]-N'-isopropyl hydrazideYield 73.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (2′-ethyl-5-fluoro-biphenyl-2-yloxy)-acetic acid (100 mg, 0.36 mmol), and tiophene-3-carboxylic acid-N′-isopropyl hydrazide (32 mg, 0.1268 mmol) in DMF (5 mL), was treated with triethylamine (0.152 ml, 1.09 mmol), HOBT (59 mg, 0.44 mmol), and EDCI (84 mg, 0.44 mmol) for 12 hours at room temperature. The reaction mixture was partitioned between 1N HCl and DCM. The organic layer was successively washed with 1N NaOH and brine, then dried over sodium sulfate, filtered, and concentrated. The crude was absorbed on silica and purified on a silica gel column with a 30-50% ethyl acetate/hexanes gradient to afford the product as a solid (41 mg, 26%). MS m/e 441.30 (M+H+)

Workup

  1. customThe reaction mixture was partitioned between 1N HCl and DCM
  2. washThe organic layer was successively washed with 1N NaOH and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude was absorbed on silica
  7. custompurified on a silica gel column with a 30-50% ethyl acetate/hexanes gradient

Sources & evidence

ORD record
ord-e8d5ac58243b49ea9fb0245f6946bc73
Source dataset
uspto-grants-2008_01
Patent number
US07317125B2

Reaction notes

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