Water → N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-6-[6-(methyloxy)-3-pyridinyl]-1H-indazole-4-carboxamide

HRID 85524

反応式

HRID 85524 の反応式
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.[CH3:27][O:28][C:29]1[N:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.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>[CH3:24][C:23]1[CH:22]=[C:21]([CH3:25])[NH:20][C:19](=[O:26])[C:18]=1[CH2:17][NH:16][C:14]([C:4]1[C:5]2[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=[C:2]([C:32]2[CH:33]=[N:34][C:29]([O:28][CH3:27])=[CH:30][CH:31]=2)[CH:3]=1)=[O:15]

参加物

7

反応物 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 545964906-bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamide

生成物 1

HCID 68210278N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-6-[6-(methyloxy)-3-pyridinyl]-1H-indazole-4-carboxamide収率 44.1%

試薬・触媒・溶媒 2

HCID 178418807HCID 178418807、化合物触媒HCID 18180031Water 1,2-dimethoxyethane溶媒

反応条件

温度
110 °C

実験手順

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 (120 mg, 0.29 mmol) and [6-(methyloxy)-3-pyridinyl]boronic acid (66 mg, 0.43 mmol) in DME/water (3 mL:1 mL). PdCl2(dppf)-CH2Cl2 (11.7 mg, 0.014 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (72.5 mg, 0.86 mmol) was added and the insoluble mixture was heated in a microwave at 110° C. for 20 min. Water was added and the solids that precipitated were filtered. DCM was added and it was purified by SiO2 chromatography (eluent: gradient 100% DCM to 80:20:2 DCM/MeOH/NH4OH). Fractions were evaporated. EtOAc was added along with some hexanes, it was sonicated and the solids that precipitated were filtered. DMF was added along with some water and the solids that precipitated were filtered and dried to afford the title compound (57 mg, 43%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.54 (s, 1H) 8.69 (d, J=2.27 Hz, 1H) 8.62 (t, J=4.80 Hz, 1H) 8.39 (s, 1H) 8.22 (dd, J=8.72, 2.65 Hz, 1H) 8.15 (s, 1H) 7.87 (s, 1H) 6.97 (d, J=8.59 Hz, 1H) 5.89 (s, 1H) 5.15 (dt, J=13.07, 6.47 Hz, 1H) 4.39 (d, J=4.80 Hz, 2H) 3.92 (s, 3H) 2.22 (s, 3H) 2.12 (s, 3H) 1.51 (s, 3H) 1.49 (s, 3H). MS(ES) [M+H]+ 446.1.

後処理

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

出典と根拠

ORDレコード
ord-0ecc8abb336b468fafa00f543dc1faba
出典データセット
uspto-grants-2014_09
特許番号
US08846935B2

関連ノート

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