Cesium carbonate → BI-135585

HRID 406695Notes

Reaction equation

HRID 406695 reaction equation
I[C:2]1[CH:7]=[CH:6][N:5]([CH3:8])[C:4](=[O:9])[CH:3]=1.[OH:10][C:11]([CH3:44])([CH3:43])[CH2:12][C@@:13]1([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[O:18][C:17](=[O:19])[N:16]([C@H:20]([C:22]2[CH:27]=[CH:26][C:25](B3OC(C)(C)C(C)(C)O3)=[CH:24][CH:23]=2)[CH3:21])[CH2:15][CH2:14]1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:10][C:11]([CH3:43])([CH3:44])[CH2:12][C@@:13]1([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[O:18][C:17](=[O:19])[N:16]([C@H:20]([C:22]2[CH:23]=[CH:24][C:25]([C:2]3[CH:7]=[CH:6][N:5]([CH3:8])[C:4](=[O:9])[CH:3]=3)=[CH:26][CH:27]=2)[CH3:21])[CH2:15][CH2:14]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 534080094-Iodo-1-methylpyridin-2(1H)-oneHCID 59532385(S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one

Product 1

HCID 44476893BI-135585Yield 28%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 4-iodo-1-methylpyridin-2(1H)-one (0.909 g, 3.76 mmol), (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one (1.5 g, 3.13 mmol), 2 M aq Cs2CO3 (3 mL, 6 mmol), and PdCl2(PPh3)2 (0.201 g, 0.282 mmol) in 1,4-dioxane (15 mL) was refluxed under N2 for 2 hours. The reaction mixture was filtered, and the filtrate was extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated to obtain the crude compound, which was purified by preparative HPLC and chiral HPLC to obtain (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one (399 mg, 28%). LC-MS and 1H NMR (CD3OD) were the same as those of product made by Method 1. The compound was recrystallized using below methods.

Workup

  1. temperaturewas refluxed under N2 for 2 hours
  2. filtrationThe reaction mixture was filtered
  3. extractionthe filtrate was extracted with EtOAc
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto obtain the crude compound, which
  8. customwas purified by preparative HPLC and chiral HPLC

Sources & evidence

ORD record
ord-bb56e96ca5e243b899fc37bf050289ee
Source dataset
uspto-grants-2014_06
Patent number
US08754076B2

Reaction notes

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