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

HRID 518480노트

반응식

HRID 518480 반응식
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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

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

반응 조건

온도
70 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-67071b2386a248eba5b3cf6b3802b01f
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115114B2

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