Trifluoroacetic acid → (2S)-2-{[(Z)-1-methyl-3-(4-methylphenyl)-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid

HRID 2300633Notes

Reaction equation

HRID 2300633 reaction equation
[NH2:1][C@@H:2]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][C:16]2[N:17]=[C:18]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[O:19][C:20]=2[CH3:21])=[CH:9][CH:8]=1)[C:3]([OH:5])=[O:4].C(O)(C(F)(F)F)=O.[CH3:35][C:36]1[CH:41]=[CH:40][C:39]([C:42](=[O:47])[CH2:43][C:44](=O)[CH3:45])=[CH:38][CH:37]=1>>[CH3:45]/[C:44](/[NH:1][C@@H:2]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][C:16]2[N:17]=[C:18]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[O:19][C:20]=2[CH3:21])=[CH:9][CH:8]=1)[C:3]([OH:5])=[O:4])=[CH:43]/[C:42]([C:39]1[CH:38]=[CH:37][C:36]([CH3:35])=[CH:41][CH:40]=1)=[O:47]

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 4326511-(4-Methylphenyl)butane-1,3-dioneHCID 18343040(2S)-2-amino-3-{4-[2-(5-methyl-2-phenyl-1,3oxazol-4-yl)ethoxy]phenyl}propanoic acid

Product 1

HCID 9828201(2S)-2-{[(Z)-1-methyl-3-(4-methylphenyl)-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid

Procedure

The title compound was prepared (as described above for the preparation of Example 2) from 790 mg (1.64 mmol) of Intermediate 45 (as the TFA salt) and 0.29 g (1.64 mmol) of Intermediate 27 (with 660 μL of DCA replacing Et3N) to yield crude product contaminated with DCA). A second silica gel chromatography column eluting with 8:1 DCM:MeOH gave 70 mg of Example 19 as a beige-colored solid: TLC (DCM/MeOH (4:1): Rf=0.58; 1H NMR (DMSO-d6, 400 MHz) δ11.43 (d, 1H, J=9.0), 7.96 (m, 2H), 7.74 (d, 2H, J=8.1), 7.54 (m, 3H), 7.24 (d, 2H, J=8.1), 7.18 (d, 2H, J=8.4), 6.87 (d, 2H, J=8.4), 5.57 (s, 1H), 4.21 (t, 2H, J=6.6), 4.08 (m, 1H), 3.23 (m, 2H), 2.95 (t, 2H, J=6.6), 2.80(dd, 1H, J=13.8, 9.0), 2.39 (s, 3H), 2.37 (s, 3H), 1.71 (s, 3H); low resolution MS (ES+)m/e 525.2 (MH+).

Workup

  1. customto yield crude product
  2. washA second silica gel chromatography column eluting with 8:1 DCM

Sources & evidence

ORD record
ord-e6a74a3031f84a76bf43a4e30d942659
Source dataset
uspto-grants-2002_12
Patent number
US06498174B1

Reaction notes

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