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

HRID 2300629Notes

Reaction equation

HRID 2300629 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].[F:28][C:29]1[C:34]([F:35])=[C:33]([F:36])[CH:32]=[CH:31][C:30]=1[C:37](=[O:41])[C:38]#[C:39][CH3:40].CCN(C(C)C)C(C)C>CO>[CH3:40]/[C:39](/[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:38]/[C:37](=[O:41])[C:30]1[CH:31]=[CH:32][C:33]([F:36])=[C:34]([F:35])[C:29]=1[F:28]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 18343040(2S)-2-amino-3-{4-[2-(5-methyl-2-phenyl-1,3oxazol-4-yl)ethoxy]phenyl}propanoic acidHCID 183763691-(2,3,4-Trifluorophenyl)-2-butyn-1-one

Product 1

HCID 9829368(2S)-2-{[(Z)-1-methyl-3-oxo-3-(2,3,4-trifluorophenyl)-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acidYield 58.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 680 mg (1.85 mmol) of Intermediate 45, 367 mg (1.85 mmol) of Intermediate 36, and 0.67 mL (3.7 mmol) of DIEA in 15 mL of MeOH was refluxed overnight (14 h). The solvent was evaporated under reduced pressure and the residue purified directly by silica gel chromatography. Elution with 5%-20% MeOH in CH2Cl2 gave 612 mg (58% yield) of the title compound as a solid: TLC (DCM/MeOH, 4/1): Rf=0.50; 1H NMR (DMSO-d6, 300 MHz) δ11.35 (d, 1H, J=9.0), 7.87 (m, 2H), 7.48 (m, 4H), 7.3 (q, 1H, J=5.4), 7.10 (d, 2H, J=8.7), 6.78 (d, 2H, J=8.7), 5.25 (s, 1H), 4.18 (m, 3H), 3.19 (m, 2H), 2.86 (t, 2H, J=6.3), 2.74 (dd, 1H, J=13.8, 9.0), 2.32 (s, 3H), 1.64 (s, 3H); low resolution MS (ES+)m/e 564.9 (MH+);

Workup

  1. temperaturewas refluxed overnight (14 h)
  2. customThe solvent was evaporated under reduced pressure
  3. customthe residue purified directly by silica gel chromatography
  4. washElution with 5%-20% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-36108459aaa447098e70f83819ffecfc
Source dataset
uspto-grants-2002_12
Patent number
US06498174B1

Reaction notes

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