تفاعل #52118

ord-86d0fc491dd246a7b4b9138f00311982

معادلة التفاعل

CCN(C(C)C)C(C)C
DIPEA
C[C@@]1(Cc2ccc(C#N)cc2)C(=O)N(c2cc(Cl)cc(Cl)c2)c2ncc(S(=O)(=O)N3CCC[C@H]3C(=O)O)n21
(S)-1-[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-α]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid
O=C(O)C(F)(F)F
trifluoroacetic acid
CN(C)C(On1nnc2ccccc21)=[N+](C)C.F[B-](F)(F)F
TBTU
C[C@@]1(Cc2ccc(C#N)cc2)C(=O)N(c2cc(Cl)cc(Cl)c2)c2ncc(S(=O)(=O)N3CCC[C@H]3C(=O)NC[C@H]3CCC(=O)O3)n21
title compound
C[C@@]1(Cc2ccc(C#N)cc2)C(=O)N(c2cc(Cl)cc(Cl)c2)c2ncc(S(=O)(=O)N3CCC[C@H]3C(=O)NC[C@H]3CCC(=O)O3)n21
(S)-1-[(R)5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-α]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid ((R)-5-oxo-tetrahydro-furan-2-ylmethyl)amide

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    غسيلwashed with water (x3), 1N HCl, and saturated NaHCO3
  2. 2
    تجفيفThe organic phase was dried over Na2SO4
  3. 3
    تركيزconcentrated
  4. 4
    workup.DISSOLUTIONThe resulting residue was dissolved in CH2Cl2
  5. 5
    workup.STIRRINGThe reaction mixture was stirred at room temperature for 3 h
  6. 6
    غسيلwashed with saturated NaHCO3 and water
  7. 7
    تجفيفThe organic phase was dried over Na2SO4
  8. 8
    تركيزconcentrated
  9. 9
    أخرىThe resulting residue was purified by silica gel preparative thin layer chromatography

الإجراء التجريبي

To a solution of (S)-1-[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-α]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (see Example 5) (0.1 g, 0.174 mmol) in anhydrous DMF was added the above mixture of amines (0.030 g), followed by TBTU (0.084 g, 0.261 mmol) followed by DIPEA (0.075 mL, 0.435 mmol). The reaction mixture was stirred at room temperature for 30 min. The reaction mixture was then diluted with EtOAc and washed with water (x3), 1N HCl, and saturated NaHCO3. The organic phase was dried over Na2SO4 and concentrated. The resulting residue was dissolved in CH2Cl2 and trifluoroacetic acid (1 eq) was added to the solution. The reaction mixture was stirred at room temperature for 3 h and washed with saturated NaHCO3 and water. The organic phase was dried over Na2SO4 and concentrated. The resulting residue was purified by silica gel preparative thin layer chromatography using CH2Cl2—MeOH (95:5) as an eluent to afford 0.063 g of the title compound as a white foam (M+1,671.1).

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US06852748B1uspto-grants-2005_02