Ethyl Acetate → benzyl N-[4-[[[2-[2,6-difluoro-4-(2-methylpropylcarbamoyl)phenyl]-2-ethoxyacetyl]amino]methyl]benzenecarboximidoyl]carbamate

HRID 1247377Notes

Reaction equation

HRID 1247377 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8](=[O:14])[NH:9][CH2:10][CH:11]([CH3:13])[CH3:12])[CH:5]=[C:4]([F:15])[C:3]=1[CH:16]([O:20][CH2:21][CH3:22])[C:17]([OH:19])=O.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.CCOC(C)=O.Cl.Cl.[CH2:53]([O:60][C:61](=[O:73])[NH:62][C:63]([C:65]1[CH:70]=[CH:69][C:68]([CH2:71][NH2:72])=[CH:67][CH:66]=1)=[NH:64])[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1>CN(C=O)C>[CH2:53]([O:60][C:61](=[O:73])[NH:62][C:63]([C:65]1[CH:66]=[CH:67][C:68]([CH2:71][NH:72][C:17](=[O:19])[CH:16]([C:3]2[C:4]([F:15])=[CH:5][C:6]([C:8](=[O:14])[NH:9][CH2:10][CH:11]([CH3:12])[CH3:13])=[CH:7][C:2]=2[F:1])[O:20][CH2:21][CH3:22])=[CH:69][CH:70]=1)=[NH:64])[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 21905565(RS)-(2,6-difluoro-4-isobutylcarbamoyl-phenyl)-ethoxy-acetic acidHCID 141089245Carbamic acid, [[4-(aminomethyl)phenyl]iminomethyl]-, phenylmethyl ester, dihydrochloride

Product 1

HCID 140474502benzyl N-[4-[[[2-[2,6-difluoro-4-(2-methylpropylcarbamoyl)phenyl]-2-ethoxyacetyl]amino]methyl]benzenecarboximidoyl]carbamateYield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(RS)-(2,6-Difluoro-4-isobutylcarbamoyl-phenyl)-ethoxy-acetic acid (71 mg) was dissolved in DMF (3.5 ml) and [(4-aminomethyl-phenyl)-imino-methyl]-carbamic acid benzyl ester dihydrochloride [Prepared according to Ch. Lila, Ph. Gloanec, L. Cadet, Y. Hervé, J. Fournier, F. Leborgne, T. J. Verbeuren, G. De Nanteuil, Synthetic Communications 1998, 28, 23, 4419–4429] (88 mg), disopropylamine (114 mg) and 2-(1H-benzotriazole-1-yl) 1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) (80 mg) were subsequently added. After 30 min stirring at rt AcOEt (10 ml) was added and the organic layer was washed with 1 N HCl (2×10 ml), H2O (10 ml) and brine. The aqueous layers were extracted with more AcOEt (10 ml). After drying (MgSO4) the solvent was evaporated and the crude product was purified by HPLC to obtain 30 mg (23%) of (RS)-[(4-{[2-(2,6-difluoro-4-isobutylcarbamoyl-phenyl)-2-ethoxy-acetylamino]-methyl}-phenyl)-imino-methyl]-carbamic acid benzyl ester. White solid. MS 581.4 ([M+H]+).

Workup

  1. additionwas added
  2. washthe organic layer was washed with 1 N HCl (2×10 ml), H2O (10 ml) and brine
  3. extractionThe aqueous layers were extracted with more AcOEt (10 ml)
  4. dry with materialAfter drying (MgSO4) the solvent
  5. customwas evaporated
  6. customthe crude product was purified by HPLC

Sources & evidence

ORD record
ord-3ca91598f45c4f1db81581ee8fe6edbd
Source dataset
uspto-grants-2006_10
Patent number
US07129238B2

Reaction notes

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