N-methyl-2-pyrrolidone → 4'-Methyl-5-(5-methyl-tetrazol-1-yl)-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide

HRID 77779

Reaction equation

HRID 77779 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([N:14]3[C:18]([CH3:19])=[N:17][N:16]=[N:15]3)[CH:11]=[C:10]([C:20]([OH:22])=O)[CH:9]=2)=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.[CH3:33][O:34][CH2:35][CH:36]([NH2:38])[CH3:37].CN1C(=O)CCC1.CCN=C=NCCCN(C)C>C(Cl)Cl.CN(C=O)C>[CH3:33][O:34][CH2:35][CH:36]([NH:38][C:20]([C:10]1[CH:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=2)[CH:13]=[C:12]([N:14]2[C:18]([CH3:19])=[N:17][N:16]=[N:15]2)[CH:11]=1)=[O:22])[CH3:37]

Participants

8

Reactant 5

HCID 13387N-methyl-2-pyrrolidoneHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 123458MethoxyisopropylamineHCID 578509354'-Methyl-5-(5-methyl-tetrazol-1-yl)-biphenyl-3-carboxylic acid

Product 1

HCID 578512554'-Methyl-5-(5-methyl-tetrazol-1-yl)-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amideYield 90%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 4′-methyl-5-(5-methyl-tetrazol-1-yl)-biphenyl-3-carboxylic acid (0.3402 mmol, 100 mg), HOBt (0.6804 mmol, 91.9 mg), 2-methoxy-1-methyl-ethylamine (0.4083 mmol, 43 μL) and NMP (1.0206 mmol, 112 μL) in CH2Cl2 (1 mL) and DMF (0.5 mL) was added EDCI (0.6804 mmol, 130.4 mg) at room temperature, and the mixture was stirred at room temperature for 18 hours. The mixture was extracted with ethyl acetate and the organic layer was washed with 2N aqueous NaOH, 1 N aqueous HCl, brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified by Flash column chromatography, eluting with n-hexane:ethyl acetate (4:1) to give 4′-methyl-5-(5-methyl-tetrazol-1-yl)-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide (white powder, 90% yield). MS (M+H)=366.

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. washthe organic layer was washed with 2N aqueous NaOH, 1 N aqueous HCl, brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by Flash column chromatography
  7. washeluting with n-hexane:ethyl acetate (4:1)

Sources & evidence

ORD record
ord-33b87137c5644306b8efb80d7344d64c
Source dataset
uspto-grants-2014_09
Patent number
US08841336B2

Linked notes

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