1,1'-Carbonyldiimidazole → 3-[[[[4'-[[2-[(tert-butoxycarbonyl)-[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]amino]-3-isobutoxy-4-biphenylyl]carbonyl]amino]sulfonyl]propyl acetate

HRID 2078669Notes

Reaction equation

HRID 2078669 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:32][C@@H:33]([C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([Cl:41])[CH:36]=1)[OH:34])[CH2:9][CH2:10][NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][C:21]([C:24]([OH:26])=O)=[C:20]([O:27][CH2:28][CH:29]([CH3:31])[CH3:30])[CH:19]=2)=[CH:14][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.N1CCCN2CCCCCC=12.[C:65]([O:68][CH2:69][CH2:70][CH2:71][S:72]([NH2:75])(=[O:74])=[O:73])(=[O:67])[CH3:66]>CN(C)C=O>[C:65]([O:68][CH2:69][CH2:70][CH2:71][S:72]([NH:75][C:24]([C:21]1[CH:22]=[CH:23][C:18]([C:15]2[CH:14]=[CH:13][C:12]([NH:11][CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:32][C@@H:33]([C:35]3[CH:40]=[CH:39][CH:38]=[C:37]([Cl:41])[CH:36]=3)[OH:34])=[CH:17][CH:16]=2)=[CH:19][C:20]=1[O:27][CH2:28][CH:29]([CH3:30])[CH3:31])=[O:26])(=[O:73])=[O:74])(=[O:67])[CH3:66]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 106074883-(Aminosulfonyl)propyl acetateHCID 67097817HCID 67097817, compound

Product 1

HCID 670975243-[[[[4'-[[2-[(tert-butoxycarbonyl)-[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]amino]-3-isobutoxy-4-biphenylyl]carbonyl]amino]sulfonyl]propyl acetateYield 44.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 4′-[[2-[(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]amino]-3-isobutoxy-4-biphenylcarboxylic acid (60.0 mg) in N,N-dimethylformamide (0.450 ml) was added 1,1′-carbonylbis-1H-imidazole (18.3 mg) and the mixture was stirred at room temperature for 1.5 hours under nitrogen atmosphere. To the mixture were added 2,3,4,6,7,8,9,10-octahydropyrimido-[1,2-a]azepine (0.0185 ml) and a solution of 3-(aminosulfonyl)propyl acetate (22.4 mg) in N,N-dimethylformamide (0.300 ml) and the mixture was stirred at room temperature for 2 days. The reaction mixture was warmed to 120° C. and stirred at the same temperature for 2 hours. After cooling to room temperature, the reaction mixture was extracted with ethyl acetate, washed with water and brine and dried over magnesium sulfate. Filtration followed by evaporation gave the crude product which was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=1/3 to 1/1) to give 3-[[[[4′-[[2-[(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]amino]-3-isobutoxy-4-biphenylyl]carbonyl]amino]sulfonyl]propyl acetate (34.1 mg) as a yellow paste.

Workup

  1. temperatureThe reaction mixture was warmed to 120° C.
  2. stirringstirred at the same temperature for 2 hours
  3. temperatureAfter cooling to room temperature
  4. extractionthe reaction mixture was extracted with ethyl acetate
  5. washwashed with water and brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationFiltration
  8. customfollowed by evaporation
  9. customgave the crude product which
  10. customwas purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=1/3 to 1/1)

Sources & evidence

ORD record
ord-f1f6816d1790498d9849d7cf4023712a
Source dataset
uspto-grants-2011_04
Patent number
US07928264B2

Reaction notes

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