HCID 86704635, compound → HCID 86704634, compound

HRID 1508586Notes

Reaction equation

HRID 1508586 reaction equation
[N:1]1([C:5]2[N:10]=[C:9]([CH2:11][N:12]3[C@@H:16]([CH3:17])[C@@H:15]([C:18]4[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=4)[O:14][C:13]3=[O:32])[C:8]([C:33]3[C:34]([CH3:47])=[C:35](/[CH:41]=[CH:42]/[C:43]([O:45]C)=[O:44])[CH:36]=[CH:37][C:38]=3[O:39][CH3:40])=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1.[H][H]>CO.[Pd]>[N:1]1([C:5]2[N:10]=[C:9]([CH2:11][N:12]3[C@@H:16]([CH3:17])[C@@H:15]([C:18]4[CH:19]=[C:20]([C:28]([F:30])([F:29])[F:31])[CH:21]=[C:22]([C:24]([F:25])([F:27])[F:26])[CH:23]=4)[O:14][C:13]3=[O:32])[C:8]([C:33]3[C:34]([CH3:47])=[C:35]([CH2:41][CH2:42][C:43]([OH:45])=[O:44])[CH:36]=[CH:37][C:38]=3[O:39][CH3:40])=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 86704635HCID 86704635, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 86704634HCID 86704634, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of methyl (2E)-3-{3-[6-(azetidin-1-yl)-2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl]-4-methoxy-2-methylphenyl}prop-2-enoate (118 mg, 0.178 mmol) in methanol (2371 μl) was added palladium on carbon (10%) (59 mg, 0.178 mmol). This mixture was placed under a balloon of hydrogen gas and purged three times with vacuum, then allow to stir at 45° C. for 1.5 hours. LC/MS indicated complete conversion to desired product. The mixture was then diluted with filtered though a plug of Celite®. The residue was concentrated to furnish the desired product as a 53/47 mixture of atropisomers. To a solution of this mixture (98 mg, 0.147 mmol) in dioxane (1996 μl) and water (499 μl) was added lithium hydroxide (35.3 mg, 1.472 mmol). The reaction was stirred at room temp for 5 hours until complete. The mixture was then concentrated in vacuo and purified on reverse phase HPLC (C-18 column, 0-90% acetonitrile in water). The pure mixture of atropisomers was then separated on a Chiral SFC (Chiralcel AD-H column, 10% EtOH in CO2). To provide both atropisomers. Atropisomer A: Mass spectrum (ESI) 652.3 (M+1). 1H NMR (500 MHz, CDCl3) (atropisomers) δ 7.85 (s, 1H), 7.73 (s, 2H), 7.19 (d, J=8.4 Hz, 1H), 7.17 (d, J=8.4 Hz, 1H), 6.75 (d, J=8.4 Hz, 1H), 6.32 (d, J=8.4 Hz, 1H), 5.69 (d, J=8.7 Hz, 1H), 4.55 (m, 1H), 4.43 (d, J=15.8 Hz, 1H), 4.10 (m, 4H), 3.72 (m, 1H), 3.65 (s, 3H), 2.97 (m, 2H), 2.64 (t, J=7.6 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H), 2.00 (s, 3H), 0.71 (d, J=6.6 Hz, 3H). Atropisomer B: Mass spectrum (ESI) 652.3 (M+1). 1H NMR (500 MHz, CDCl3) (atropisomers) δ 7.84 (s, 1H), 7.68 (s, 2H), 7.20 (d, J=7.9 Hz, 1H), 7.16 (d, J=8.5 Hz, 1H), 6.77 (d, J=8.5 Hz, 1H), 6.32 (d, J=7.6 Hz, 1H), 5.51 (d, J=8.0 Hz, 1H), 4.62 (d, J=15.9 Hz, 1H), 4.22 (m, 1H), 4.09 (m, 4H), 3.73 (m, 1H), 2.95 (m, 2H), 2.64 (t, J=7.5 Hz, 2H), 2.43 (t, J=7.2 Hz, 2H), 2.02 (s, 3H), 0.68 (d, J=6.3 Hz, 3H).

Workup

  1. custompurged three times with vacuum
  2. additionThe mixture was then diluted
  3. filtrationwith filtered though a plug of Celite®
  4. concentrationThe residue was concentrated

Sources & evidence

ORD record
ord-3717418412c54d5ba89563472efd95e7
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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