Cesium carbonate → HCID 58109473, compound

HRID 2046003Notes

Reaction equation

HRID 2046003 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.[Cl:36][C:37]1[CH:42]=[C:41](Cl)[N:40]=[CH:39][N:38]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:36][C:37]1[N:38]=[CH:39][N:40]=[C:41]([C:20]2[CH:21]=[CH:22][C:17]([C@@H:15]([N:11]3[CH2:10][CH2:9][C@@:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)([CH2:32][CH2:33][CH2:34][OH:35])[O:13][C:12]3=[O:14])[CH3:16])=[CH:18][CH:19]=2)[CH:42]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 709434,6-DichloropyrimidineHCID 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 58109473HCID 58109473, compoundYield 68.6%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture 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 (30 mg, 0.062 mmol), 4,6-dichloropyrimidine (12 mg, 0.081 mmol), and 2 M aqueous Cs2CO3 (1.0 mL) in dry THF (2 mL) was added Pd(dppf)Cl2 (6 mg, 0.00621 mmol) under N2 atmosphere. The mixture was heated to reflux for 2 hours. Then the solvent was evaporated, and the residue was purified by preparative TLC to afford (R)-3-((S)-1-(4-(6-chloropyrimidin-4-yl)phenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one (20 mg, yield 68%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 2 hours
  3. customThen the solvent was evaporated
  4. customthe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-3a89b7de42e24f3f82fa985e8e7345a4
Source dataset
uspto-grants-2013_11
Patent number
US08592410B2

Reaction notes

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