Diisopropylethylamine → tert-butyl 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetate

HRID 923569Notes

Reaction equation

HRID 923569 reaction equation
[OH:1][NH:2][C:3]([C:5]1[CH:44]=[CH:43][C:8]([CH2:9][N:10]([CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[C:11](=[O:34])[C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:33])[CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][C:22]=3[C:29]([F:32])([F:31])[F:30])=[CH:14][CH:13]=2)=[CH:7][CH:6]=1)=[NH:4].CCN(C(C)C)C(C)C.[CH3:54][C:55]1[CH:60]=[CH:59][C:58]([C:61]2[CH:66]=[CH:65][C:64]([C:67](Cl)=O)=[CH:63][CH:62]=2)=[CH:57][CH:56]=1>O1CCOCC1.C([O-])(O)=O.[Na+]>[CH3:28][O:27][C:24]1[CH:25]=[CH:26][C:21]([CH2:20][C:19]([NH:18][C:15]2[CH:16]=[CH:17][C:12]([C:11]([N:10]([CH2:35][C:36]([O:38][C:39]([CH3:41])([CH3:40])[CH3:42])=[O:37])[CH2:9][C:8]3[CH:7]=[CH:6][C:5]([C:3]4[N:4]=[C:54]([C:55]5[CH:60]=[CH:59][C:58]([C:61]6[CH:66]=[CH:65][C:64]([CH3:67])=[CH:63][CH:62]=6)=[CH:57][CH:56]=5)[O:1][N:2]=4)=[CH:44][CH:43]=3)=[O:34])=[CH:13][CH:14]=2)=[O:33])=[C:22]([C:29]([F:31])([F:30])[F:32])[CH:23]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 140418444'-Methyl-[1,1'-biphenyl]-4-carbonyl chlorideHCID 178490478HCID 178490478, compound

Product 1

HCID 71112076tert-butyl 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetateYield 40%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

Prepared using General Procedure 20: To a stirring solution of tert-butyl 2-(N-(4-(N-hydroxycarbamimidoyl)benzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetate INT-33 (104 mg, 0.169 mmol) and DIEA (47.0 μL, 0.254 mmol) in dioxane (4 mL) was added 4′-methyl-[1,1′-biphenyl]-4-carbonyl chloride (39.0 mg, 0.169 mmol) in dioxane (1 mL). After stirring at room temperature for 30 min, the reaction mixture was heated to 120° C. for 2 h. The reaction mixture was allowed to cool to room temperature then diluted with NaHCO3 (20 mL) and extracted with DCM (3×20 mL). The combined organic extracts were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (EA/isohexanes) to yield 54 mg (40%) of tert-butyl 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetate INT-34. LCMS-ESI (m/z) calculated for C45H41F3N4O6: 791; no m/z observed, tR=1.70 min (Method 10).

Workup

  1. customPrepared
  2. temperaturethe reaction mixture was heated to 120° C. for 2 h
  3. temperatureto cool to room temperature
  4. extractionextracted with DCM (3×20 mL)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography (EA/isohexanes)

Sources & evidence

ORD record
ord-46050526db92495e89c4edcc7e7fc399
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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