Cesium carbonate → HCID 58109546, compound

HRID 1046198Notes

Reaction equation

HRID 1046198 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]2([CH2:32][CH2:33][CH2:34][OH:35])[O:13][C:12](=[O:14])[N:11]([C@H:15]([C:17]3[CH:22]=[CH:21][C:20](B4OC(C)(C)C(C)(C)O4)=[CH:19][CH:18]=3)[CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Br[C:37]1[CH:38]=[N:39][C:40]([CH3:43])=[N:41][CH:42]=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>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C@:8]2([CH2:32][CH2:33][CH2:34][OH:35])[O:13][C:12](=[O:14])[N:11]([C@H:15]([C:17]3[CH:18]=[CH:19][C:20]([C:37]4[CH:38]=[N:39][C:40]([CH3:43])=[N:41][CH:42]=4)=[CH:21][CH:22]=3)[CH3:16])[CH2:10][CH2:9]2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 143877445-Bromo-2-methylpyrimidineHCID 58109220(R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-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 58109546HCID 58109546, compoundYield 44.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one (61 mg, 0.13 mmol), 5-bromo-2-methylpyrimidine (18 mg, 0.11 mmol), PdCl2(PPh3)2 (6 mg, 10%) and aqueous solution of Cs2CO3 (2 mol/L, 0.13 mL) in 1,4-dioxane (1 mL) was heated to reflux overnight. The reaction was quenched with water. The organic layer was separated, dried and concentrated to give the residue, which was purified by column chromatography to give (R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-3-((S)-1-(4-(2-methylpyrimidin-5-yl)phenyl)ethyl)-1,3-oxazinan-2-one (22 mg, 39%). 1H NMR (CDCl3): 1.42 (m, 1H), 1.48 (d, 3H), 1.67 (m, 1H), 1.71-1.99 (m, 4H), 2.11-2.41 (m, 3H), 2.52 (s, 3H), 2.72 (m, 1H), 3.53 (m, 2H), 5.62 (m, 1H), 6.89-7.04 (m, 4H), 7.15-7.33 (m, 4H), 8.70 (s, 2H). LC-MS Method 2 tR=1.184, m/z=450; 1H NMR (CDCl3) 1.20 (d, 1H), 1.27-1.40 (m, 1H), 1.49 (d, 3H), 1.59-1.70 (m, 1H), 1.71-2.07 (m, 4H), 2.11-2.33 (m, 3H), 2.70 (s, 3H), 2.90 (m, 1H), 3.46-3.61 (t, 2H), 5.67 (m, 1H), 6.90-7.11 (m, 4H), 7.26 (m, 4H), 8.57-8.83 (s, 2H).

Workup

  1. temperatureto reflux overnight
  2. customThe reaction was quenched with water
  3. customThe organic layer was separated
  4. customdried
  5. concentrationconcentrated
  6. customto give the residue, which
  7. customwas purified by column chromatography

Sources & evidence

ORD record
ord-2333f57bb5ed4a6cba30f2a534ce402d
Source dataset
uspto-grants-2013_10
Patent number
US08569292B2

Reaction notes

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