Hydrochloric Acid → HCID 67097058, compound

HRID 2078645

Reaction equation

HRID 2078645 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:30][C@@H:31]([C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([Cl:39])[CH:34]=1)[OH:32])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23](O)=[O:24])=[C:19]([S:26][CH:27]([CH3:29])[CH3:28])[CH:18]=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:40]([O:43][CH2:44][CH2:45][CH2:46][S:47]([NH2:50])(=[O:49])=[O:48])(=[O:42])[CH3:41].C1CCN2C(=NCCC2)CC1.Cl>O1CCCC1.C(OCC)(=O)C>[C:40]([O:43][CH2:44][CH2:45][CH2:46][S:47]([NH:50][C:23]([C:20]1[CH:21]=[CH:22][C:17]([C:14]2[CH:13]=[CH:12][C:11]([CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:30][C@@H:31]([C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([Cl:39])[CH:34]=3)[OH:32])=[CH:16][CH:15]=2)=[CH:18][C:19]=1[S:26][CH:27]([CH3:29])[CH3:28])=[O:24])(=[O:48])=[O:49])(=[O:42])[CH3:41]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 106074883-(Aminosulfonyl)propyl acetateHCID 67097872HCID 67097872, compound

Product 1

HCID 67097058HCID 67097058, compoundYield 37.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4′-[2-[(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]-3-(isopropylthio)-4-biphenylcarboxylic acid (150 mg) in tetrahydrofuran (1.5 ml) was added N,N′-carbonyldiimidazole (64 mg) and stirred at room temperature for 30 minutes. To the mixture were added 3-(aminosulfonyl)propyl acetate (67 mg) and 1,8-diazabicyclo[5.4.0]-7-undecene (55 μl) and stirred at room temperature, and then stirred at 50° C. for 3 hours. The reaction mixture was poured into 0.1N hydrochloric acid and ethyl acetate and the organic layer was separated. The organic layer was washed with water and brine, dried over magnesium sulfate and concentrated in vacuo to give 3-[[[[4′-[2-[(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]-3-(isopropylthio)-4-biphenylyl]carbonyl]amino]sulfonyl]propyl acetate (72 mg). To a solution of the product (72 mg) in methanol (2.0 ml) and tetrahydrofuran (2.0 ml) was added sodium hydroxide aqueous solution (1N, 532 μl) and stirred at room temperature for 10 minutes. To the mixture was added hydrochloric acid aqueous solution (1N, 532 μl) and diluted with ethyl acetate. The solution was poured into water and ethyl acetate and the organic layer was separated. The organic layer was washed with water and brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified with silica gel column chromatography to give tert-butyl [(2R)-2-(3-chlorophenyl)-2-hydroxyethyl][2-[4′-[[[(3-hydroxypropyl)sulfonyl]amino]carbonyl]-3′-(isopropylthio)-4-biphenylyl]-ethyl]carbamate (49 mg).

Workup

  1. stirringstirred at room temperature
  2. stirringstirred at 50° C. for 3 hours
  3. customthe organic layer was separated
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-306a576d3f0140aaa444b506c1665954
Source dataset
uspto-grants-2011_04
Patent number
US07928264B2

Linked notes

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