Cesium carbonate → (R)-3-((S)-1-(4-(6-aminopyridin-3-yl)phenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one

HRID 406674Notes

Reaction equation

HRID 406674 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]2[CH2:15][CH2:14][C@@:13]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)([CH2:16][CH2:17][CH2:18][OH:19])[O:12][C:11]2=[O:27])[CH3:9])=[CH:4][CH:3]=1.[NH2:28][C:29]1[N:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=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>[NH2:28][C:29]1[N:34]=[CH:33][C:32]([C:2]2[CH:3]=[CH:4][C:5]([C@@H:8]([N:10]3[CH2:15][CH2:14][C@@:13]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)([CH2:16][CH2:17][CH2:18][OH:19])[O:12][C:11]3=[O:27])[CH3:9])=[CH:6][CH:7]=2)=[CH:31][CH:30]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 22396308(6-Aminopyridin-3-yl)boronic acidHCID 59532370(R)-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxy-propyl)-1,3-oxazinan-2-one

Product 1

HCID 59635760(R)-3-((S)-1-(4-(6-aminopyridin-3-yl)phenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of (R)-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one (520 mg, 1.2 mmol) and 6-aminopyridin-3-ylboronic acid (280 mg, 1.44 mmol), Pd(Ph3P)2Cl2 (100 mg), and aq Cs2CO3 solution (3 mL, 2M) in 1,4-dioxane (20 mL) was stirred and heated to reflux for 2 h. The organic phase was separated, and concentrated to give crude product, which was purified by preparative TLC to give (R)-3-((S)-1-(4-(6-aminopyridin-3-yl)phenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxy propyl)-1,3-oxazinan-2-one. (400 mg, 74%).

Workup

  1. temperatureheated
  2. temperatureto reflux for 2 h
  3. customThe organic phase was separated
  4. concentrationconcentrated
  5. customto give crude product, which
  6. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-7a5fc36b49e74d0d940640023f090c4b
Source dataset
uspto-grants-2014_06
Patent number
US08754076B2

Reaction notes

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