Sodium Bicarbonate → 4-[5-(2,4-Difluorophenoxy)-2-methylsulfonylpyrimidin-4-yl]-6-methylfuro[2,3-c]pyridin-7-one

HRID 518480Notes

Reaction equation

HRID 518480 reaction equation
Cl[C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[F:16])=[CH:6][N:5]=[C:4]([S:17]([CH3:20])(=[O:19])=[O:18])[N:3]=1.Br[C:22]1[C:23]2[CH:32]=[C:31](F)[O:30][C:24]=2[C:25](=[O:29])[N:26]([CH3:28])[CH:27]=1.C([O-])(O)=O.[Na+]>O1CCOCC1.O.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]>[F:16][C:10]1[CH:11]=[C:12]([F:15])[CH:13]=[CH:14][C:9]=1[O:8][C:7]1[C:2]([C:22]2[C:23]3[CH:32]=[CH:31][O:30][C:24]=3[C:25](=[O:29])[N:26]([CH3:28])[CH:27]=2)=[N:3][C:4]([S:17]([CH3:20])(=[O:19])=[O:18])=[N:5][CH:6]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 1180215444-Chloro-5-(2,4-difluorophenoxy)-2-methylsulfonylpyrimidineHCID 1180224594-Bromo-2-fluoro-6-methylfuro[2,3-c]pyridin-7-one

Product 1

HCID 1180220064-[5-(2,4-Difluorophenoxy)-2-methylsulfonylpyrimidin-4-yl]-6-methylfuro[2,3-c]pyridin-7-oneYield 79.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4-chloro-5-(2,4-difluorophenoxy)-2-methylsulfonylpyrimidine (155 mg, 0.48 mmol), 4-bromo-2-fluoro-6-methylfuro[2,3-c]pyridin-7-one (120 mg, 0.44 mmol), NaHCO3 (92 mg, 1.1 mmol), Pd(dppf)Cl2 (32 mg, 10%) in dioxane/H2O (4 mL/200 uL) was bubbled with nitrogen for 7 min. The sealed vial was stirred at 70° C. for 8 h. LCMS analysis showed complete consumption of the limiting reagent. The reaction mixture was filtered through a short plug of celite; the celite plug was washed with DCM. The filtrate was concentrated in vacuo. The resulting residue was purified by silica gel column chromatography using a gradient of EtOAc (10 to 100%) in DCM to afford the title compound (151 mg, 79%) as a yellow solid. LCMS (M+H)+=434.

Workup

  1. customwas bubbled with nitrogen for 7 min
  2. customconsumption of the limiting reagent
  3. filtrationThe reaction mixture was filtered through a short plug of celite
  4. washthe celite plug was washed with DCM
  5. concentrationThe filtrate was concentrated in vacuo
  6. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-67071b2386a248eba5b3cf6b3802b01f
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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