Trifluoroacetic acid → 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(2-(4'-methyl-[1,1'-biphenyl]-4-yl)oxazol-4-yl)benzyl)benzamido)acetic acid

HRID 923584Notes

Reaction equation

HRID 923584 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][CH:10]=[C:11]([C:13]3[CH:52]=[CH:51][C:16]([CH2:17][N:18]([CH2:43][C:44]([O:46]C(C)(C)C)=[O:45])[C:19](=[O:42])[C:20]4[CH:25]=[CH:24][C:23]([NH:26][C:27](=[O:41])[CH2:28][C:29]5[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][C:30]=5[C:37]([F:40])([F:39])[F:38])=[CH:22][CH:21]=4)=[CH:15][CH:14]=3)[N:12]=2)=[CH:4][CH:3]=1.[C:53](O)([C:55](F)(F)F)=O>C(Cl)Cl>[CH3:36][O:35][C:32]1[CH:33]=[CH:34][C:29]([CH2:28][C:27]([NH:26][C:23]2[CH:24]=[CH:25][C:20]([C:19]([N:18]([CH2:43][C:44]([OH:46])=[O:45])[CH2:17][C:16]3[CH:15]=[CH:14][C:13]([C:11]4[N:12]=[C:8]([C:5]5[CH:6]=[CH:7][C:2]([C:2]6[CH:7]=[CH:6][C:53]([CH3:55])=[CH:4][CH:3]=6)=[CH:3][CH:4]=5)[O:9][CH:10]=4)=[CH:52][CH:51]=3)=[O:42])=[CH:21][CH:22]=2)=[O:41])=[C:30]([C:37]([F:38])([F:40])[F:39])[CH:31]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71076598tert-butyl 2-(N-(4-(2-(4-bromophenyl)oxazol-4-yl)benzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetate

Product 1

HCID 710769122-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(2-(4'-methyl-[1,1'-biphenyl]-4-yl)oxazol-4-yl)benzyl)benzamido)acetic acidYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of tert-butyl 2-(N-(4-(2-(4-bromophenyl)oxazol-4-yl)benzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetate INT-45 (118 mg, 0.152 mmol) in THF (1 mL) and acetonitrile (1 mL) were added sodium carbonate (0.30 mL, 0.30 mmol, 1 M aqueous solution) and p-tolylboronic acid (25.0 mg, 0.18 mmol). The reaction mixture was de-gassed and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (5.50 mg, 7.60 μmol) was added. The reaction mixture was heated in a microwave at 130° C. for 30 min. The reaction mixture was diluted with DCM (4 mL) and NaHCO3 (10 mL), stirred for 15 min and split through a hydrophobic frit. The organics were evaporated and purified by column chromatography (EA/isohexanes) to yield tert-butyl 2-(N-(4-(2-(4-bromophenyl)oxazol-4-yl)benzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetate. To tert-butyl 2-(N-(4-(2-(4-bromophenyl)oxazol-4-yl)benzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetate in DCM (2 mL) was added TFA (2 mL) and the reaction mixture was stirred at room temperature for 30 min. The reaction mixture was evaporated and re-slurried from acetonitrile (4 mL) to afford 59 mg (53%) of 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(2-(4′-methyl-[1,1′-biphenyl]-4-yl)oxazol-4-yl)benzyl)benzamido)acetic acid 364 as a white solid. LCMS-ESI (m/z) calculated for C42H34F3N3O6: 733; found 734 [M+H]+, tR=9.36 min (Method 9). 1H NMR (400 MHz, DMSO) δ 12.76 (s, 1H), 10.34 (s, 1H), 8.75 (s, 1H), 8.13 (d, J=6.7 Hz, 2H), 7.90-7.85 (m, 4H), 7.70-7.59 (m, 4H), 7.50-7.42 (m, 2H), 7.41-7.31 (m, 5H), 7.25-7.16 (m, 2H), 4.70 (s, 1H), 4.62 (s, 1H), 4.02 (s, 1H), 3.92 (s, 1H), 3.86 (s, 2H), 3.83 (s, 3H), 2.37 (s, 3H).

Workup

  1. customThe reaction mixture was evaporated

Sources & evidence

ORD record
ord-c1697fb327664fbf8df4a060559c2d48
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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