1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-(3-((3,5-Dichloro-N-((4'-fluorobiphenyl-4-yl)methyl)-2-hydroxyphenylsulfonamido)methyl)benzyl)-N-Isobutyl-2-phenoxybenzamide

HRID 1889681Notes

Reaction equation

HRID 1889681 reaction equation
[Cl:1][C:2]1[C:3]([OH:40])=[C:4]([S:9]([N:12]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=3)=[CH:29][CH:28]=2)[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][NH:21][CH2:22][CH:23]([CH3:25])[CH3:24])[CH:15]=2)(=[O:11])=[O:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1.CCN(C(C)C)C(C)C.[O:50]([C:57]1[CH:65]=[CH:64][CH:63]=[CH:62][C:58]=1[C:59]([OH:61])=O)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.CCN=C=NCCCN(C)C>C(#N)C.C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([OH:40])=[C:4]([S:9]([N:12]([CH2:13][C:14]2[CH:15]=[C:16]([CH:17]=[CH:18][CH:19]=2)[CH2:20][N:21]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:59](=[O:61])[C:58]2[CH:62]=[CH:63][CH:64]=[CH:65][C:57]=2[O:50][C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH2:26][C:27]2[CH:28]=[CH:29][C:30]([C:33]3[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=3)=[CH:31][CH:32]=2)(=[O:11])=[O:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 752372-Phenoxybenzoic acidHCID 81531DiisopropylethylamineHCID 585313773,5-Dichloro-N-((4'-fluorobiphenyl-4-yl)methyl)-2-hydroxy-N-(3-((isobutyl amino)methyl)benzyl)benzene sulfonamide

Product 1

HCID 58531485N-(3-((3,5-Dichloro-N-((4'-fluorobiphenyl-4-yl)methyl)-2-hydroxyphenylsulfonamido)methyl)benzyl)-N-Isobutyl-2-phenoxybenzamideYield 50%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

3,5-Dichloro-N-((4′-fluorobiphenyl-4-yl)methyl)-2-hydroxy-N-(3-((isobutyl amino)methyl)benzyl)benzene sulfonamide (0.04 g, 0.066 mmol, 1 eq) was dissolved in acetonitrile. DIPEA (0.034 mL, 0.198 mmol, 3 eq) was added to the solution followed by 2-phenoxy benzoic acid (0.014 g, 0.066 mmol, 1 eq), EDCI (0.018 g, 0.099 mmol, 1.5 eq) and HOIST (0.013 g, 0.099 mmol, 1.5 eq). The reaction mixture was stirred at ambient temperature for 12 h and concentrated to remove all the volatiles. The residue obtained was dissolved in ethyl acetate and the organic layer was washed with water. The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by preparative HPLC to afford the title compound (0.025 g, 50%). 1H NMR (400 MHz, DMSO-d6) δ 0.64-0.65 (d, 3H), 0.74-0.78 (t, 3H), 1.74 (s, 1H), 1.9 (t, 1H), 3.6 (t, 1H), 3.8 (t, 1H), 4.2 (m, 2H), 4.41-4.45 (m, 4H), 6.86-6.93 (m, 3H), 6.92-6.99 (m, 3H), 7.00-7.13 (m, 7H), 7.14-7.26 (m, 3H), 7.28-7.39 (m, 5H), 7.44-7.47 (d, 1H), 7.54-7.61 (m, 3H), 7.73-7.74 (d, 1H), 7.83-7.84 (d, 1H). MS (ESI): 798.7 (M+H)+.

Workup

  1. concentrationconcentrated
  2. customto remove all the volatiles
  3. customThe residue obtained
  4. washthe organic layer was washed with water
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-36126c2498684a8e8dd9082f13fb7c76
Source dataset
uspto-grants-2013_08
Patent number
US08501992B2

Reaction notes

Loading…