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

HRID 518480笔记

反应方程式

HRID 518480 反应方程式
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

参与物

6

反应物 3

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

产物 1

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

试剂、催化剂与溶剂 2

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

反应条件

温度
70 °C

实验过程

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.

后处理

  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

来源与证据

ORD记录
ord-67071b2386a248eba5b3cf6b3802b01f
来源数据集
uspto-grants-2015_08
专利号
US09115114B2

反应笔记

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