Diisopropylethylamine → 2-(4'-methyl-[1,1'-biphenyl]-4-yl)-2-oxoethyl 4-((N-(2-(tert-butoxy)-2-oxoethyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)methyl)benzoate

HRID 923574Notes

Reaction equation

HRID 923574 reaction equation
[C:1]([O:5][C:6](=[O:43])[CH2:7][N:8]([CH2:33][C:34]1[CH:42]=[CH:41][C:37]([C:38]([OH:40])=[O:39])=[CH:36][CH:35]=1)[C:9](=[O:32])[C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17](=[O:31])[CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=2[C:27]([F:30])([F:29])[F:28])=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].Br[CH2:45][C:46]([C:48]1[CH:53]=[CH:52][C:51]([C:54]2[CH:59]=[CH:58][C:57]([CH3:60])=[CH:56][CH:55]=2)=[CH:50][CH:49]=1)=[O:47].CCN(C(C)C)C(C)C>C(#N)C>[C:1]([O:5][C:6](=[O:43])[CH2:7][N:8]([CH2:33][C:34]1[CH:42]=[CH:41][C:37]([C:38]([O:40][CH2:45][C:46]([C:48]2[CH:53]=[CH:52][C:51]([C:54]3[CH:59]=[CH:58][C:57]([CH3:60])=[CH:56][CH:55]=3)=[CH:50][CH:49]=2)=[O:47])=[O:39])=[CH:36][CH:35]=1)[C:9](=[O:32])[C:10]1[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:31])[CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=2[C:27]([F:28])([F:29])[F:30])=[CH:14][CH:15]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 135319782-Bromo-4'(-p-tolyl)acetophenoneHCID 710768754-((N-(2-(tert-butoxy)-2-oxoethyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)methyl)benzoic acid

Product 1

HCID 711117682-(4'-methyl-[1,1'-biphenyl]-4-yl)-2-oxoethyl 4-((N-(2-(tert-butoxy)-2-oxoethyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)methyl)benzoateYield 91%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirring suspension of 4-((N-(2-(tert-butoxy)-2-oxoethyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)methyl)benzoic acid INT-37 (207 mg, 0.345 mmol) and 2-bromo-1-(4′-methyl-[1,1′-biphenyl]-4-yl)ethanone (100 mg, 0.345 mmol) in acetonitrile (4 mL) at 0° C. was added DIEA (70.0 μl, 0.379 mmol). The reaction mixture was allowed to slowly warm to room temperature and stirred for 16 h. The reaction mixture was poured onto citric acid (50 mL, 0.1 N aqueous solution) and extracted with EA (3×20 mL). The combined organic extracts were washed successively with NaHCO3 (20 mL), brine (20 mL) then dried over MgSO4 and concentrated. The crude product was purified by column chromatography (EA/isohexanes) to yield 254 mg (91%) of 2-(4′-methyl-[1,1′-biphenyl]-4-yl)-2-oxoethyl 4-((N-(2-(tert-butoxy)-2-oxoethyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)methyl)benzoate INT-38 as a white foam. LCMS-ESI (m/z) calculated for C46H43F3N2O8: 808; found 831 [M+Na]+, tR=3.10 min (Method 10).

Workup

  1. additionThe reaction mixture was poured onto citric acid (50 mL, 0.1 N aqueous solution)
  2. extractionextracted with EA (3×20 mL)
  3. washThe combined organic extracts were washed successively with NaHCO3 (20 mL), brine (20 mL)
  4. dry with materialthen dried over MgSO4
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography (EA/isohexanes)

Sources & evidence

ORD record
ord-177635f9acdb42369e30aa03212f8100
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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