Sodium Carbonate → (S)-4-(6-(5-fluoropyridin-3-yl)-2-(methylthio)pyrimidin-4-yl)-3-methylmorpholine

HRID 1771525Notes

Reaction equation

HRID 1771525 reaction equation
Cl[C:2]1[N:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][C@@H:11]2[CH3:16])[CH:3]=1.[F:17][C:18]1[CH:19]=[C:20](B2OC(C)(C)C(C)(C)O2)[CH:21]=[N:22][CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.CCO.C(Cl)Cl>[F:17][C:18]1[CH:19]=[C:20]([C:2]2[N:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]([N:10]3[CH2:15][CH2:14][O:13][CH2:12][C@@H:11]3[CH3:16])[CH:3]=2)[CH:21]=[N:22][CH:23]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 164142683-Fluoro-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 86691142(S)-4-(6-chloro-2-(methylthio)pyrimidin-4-yl)-3-methylmorpholine2×

Product 1

HCID 67382782(S)-4-(6-(5-fluoropyridin-3-yl)-2-(methylthio)pyrimidin-4-yl)-3-methylmorpholineYield 104%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 86587095Dimethoxyethane ethanol waterSolvent

Procedure

A mixture of (S)-4-(6-chloro-2-(methylthio)pyrimidin-4-yl)-3-methylmorpholine (intermediate 4) (850 mg, 3.0 mmol crude), 5-fluoropyridine-3-boronic acid pinacol ester (703 mg, 3.15 mmol), bis(diphenylphosphino)-ferrocenedichloropalladium(II):DCM complex (125 mg, 0.15 mmol) and sodium carbonate (954 mg, 9.0 mmol) in DME/H2O/EtOH (7:3:2, 12 mL) was heated in the microwave at 100° C. for 60 min. The mixture was then diluted with DCM (80 mL), washed with water (150 mL), the organic layer passed through a PTFE hydrophobic frit and the solvent removed in vacuo to yield a dark brown oil (1.0 g) used without future purification.

Workup

  1. washwashed with water (150 mL)
  2. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-e507247cc16f4ec4b76edb0b4195ba22
Source dataset
uspto-grants-2016_02
Patent number
US09249129B2

Reaction notes

Loading…