聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯] → 6-[6-(Acetylamino)-3-pyridinyl]-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-indazole-4-carboxamide

HRID 85521

反应方程式

HRID 85521 反应方程式
Br[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.CC1(C)C(C)(C)OB([C:35]2[CH:36]=[CH:37][C:38]([NH:41][C:42](=[O:44])[CH3:43])=[N:39][CH:40]=2)O1.C(=O)(O)[O-].[Na+].O>COCCOC.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].C(Cl)Cl>[C:42]([NH:41][C:38]1[N:39]=[CH:40][C:35]([C:2]2[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]3[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=3[CH3:24])=[O:15])[C:5]3[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=3[CH:10]=2)=[CH:36][CH:37]=1)(=[O:44])[CH3:43]

参与物

7

反应物 4

HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]HCID 516892碳酸氢钠HCID 177502022-乙酰氨基吡啶-5-硼酸频哪醇酯HCID 545964906-bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamide

产物 1

HCID 682102886-[6-(Acetylamino)-3-pyridinyl]-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-indazole-4-carboxamide收率 80.2%

试剂、催化剂与溶剂 2

HCID 178418807HCID 178418807，化合物催化剂HCID 18180031Water 1,2-dimethoxyethane溶剂

反应条件

温度
120 °C

实验过程

In a 25 mL sealable tube under nitrogen were combined 6-bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-indazole-4-carboxamide (110 mg, 0.24 mmol), N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl]acetamide (104 mg, 0.4 mmol) in DME/water (3 mL:1 mL). PdCl2(dppf)-CH2Cl2 (10.76 mg, 0.013 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (66.4 mg, 0.79 mmol) was added, the vessel was sealed, and the insoluble mixture was heated in a microwave at 120° C. for min. Water was added and the solids that precipitated were filtered off. DCM was added to the solids and it was purified by SiO2 chromatography (eluent: gradient 100% DCM to 80:20:2 DCM/MeOH/NH4OH). Fractions were evaporated. EtOAc was added, it was sonicated and the solids that precipitated were filtered, washed with hexanes and dried to afford the title compound (91 mg, 72%) as a light beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.54 (s, 1H) 10.65 (s, 1H) 8.84 (d, J=2.27 Hz, 1H) 8.64 (t, J=4.93 Hz, 1H) 8.39 (s, 1H) 8.25-8.30 (m, 1H) 8.15-8.24 (m, 2H) 7.89-7.93 (m, 1H) 5.89 (s, 1H) 5.18 (quin, J=6.63 Hz, 1H) 4.40 (d, J=4.80 Hz, 2H) 2.22 (s, 3H) 2.13 (s, 3H) 2.12 (s, 3H) 1.51 (s, 3H) 1.50 (s, 3H). MS(ES) [M+H]+ 473.1.

后处理

  1. customIn a 25 mL sealable tube under nitrogen were combined
  2. customthe resulting mixture was degassed with nitrogen for 10 min
  3. customthe vessel was sealed
  4. customthe solids that precipitated
  5. filtrationwere filtered off
  6. additionDCM was added to the solids and it
  7. customwas purified by SiO2 chromatography (eluent: gradient 100% DCM to 80:20:2 DCM/MeOH/NH4OH)
  8. customFractions were evaporated
  9. additionEtOAc was added
  10. customit was sonicated
  11. customthe solids that precipitated
  12. filtrationwere filtered
  13. washwashed with hexanes
  14. customdried

来源与证据

ORD记录
ord-6ca45feba0804128be7d1fa1c414a9ed
来源数据集
uspto-grants-2014_09
专利号
US08846935B2

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