Sodium Bicarbonate → 1-isopropyl-3-methyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-6-(2-(4-methylpiperazin-1-yl)pyridin-4-yl)-1H-indazole-4-carboxamide

HRID 85485ノート

反応式

HRID 85485 の反応式
Br[C:2]1[CH:3]=[C:4]([C:15]([NH:17][CH2:18][C:19]2[C:20](=[O:29])[NH:21][C:22]([CH3:28])=[CH:23][C:24]=2[CH2:25][CH2:26][CH3:27])=[O:16])[C:5]2[C:6]([CH3:14])=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.[CH3:30][N:31]1[CH2:36][CH2:35][N:34]([C:37]2[CH:42]=[C:41](B3OC(C)(C)C(C)(C)O3)[CH:40]=[CH:39][N:38]=2)[CH2:33][CH2:32]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].C(Cl)Cl>[CH:11]([N:8]1[C:9]2[CH:10]=[C:2]([C:41]3[CH:40]=[CH:39][N:38]=[C:37]([N:34]4[CH2:33][CH2:32][N:31]([CH3:30])[CH2:36][CH2:35]4)[CH:42]=3)[CH:3]=[C:4]([C:15]([NH:17][CH2:18][C:19]3[C:20](=[O:29])[NH:21][C:22]([CH3:28])=[CH:23][C:24]=3[CH2:25][CH2:26][CH3:27])=[O:16])[C:5]=2[C:6]([CH3:14])=[N:7]1)([CH3:13])[CH3:12]

参加物

6

反応物 3

HCID 516892Sodium BicarbonateHCID 27695372-(4-Methylpiperazin-1-yl)pyridine-4-boronic acid, pinacol esterHCID 545962236-bromo-1-isopropyl-3-methyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide

生成物 1

HCID 545962981-isopropyl-3-methyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-6-(2-(4-methylpiperazin-1-yl)pyridin-4-yl)-1H-indazole-4-carboxamide収率 32.2%

試薬・触媒・溶媒 2

HCID 178418807HCID 178418807、化合物触媒HCID 218864351,4-Dioxane--water (1/1)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-3-methyl-1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (85 mg, 0.19 mmol), 1-methyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl]piperazine (72.9 mg, 0.24 mmol) in dioxane/water (3 mL:1 mL). PdCl2(dppf)-CH2Cl2 adduct (7.6 mg, 0.0093 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (46.6 mg, 0.55 mmol) was added, the vessel was sealed, and the insoluble mixture was heated in a microwave at 110° C. for 20 min. The mixture was evaporated, DCM was added and the contents purified by SiO2 chromatography (eluent: gradient 0 to 80:20:2 DCM/MeOH/NH4OH). The collected product was suspended in EtOAc along with some hexanes. The contents were sonicated and solids that precipitated were filtered. Acetonitrile was added, the solids were triturated, and again filtered. The collected solid was then suspended in DMF along with some water and then allowed to sit at room temperature overnight. Solids that precipitated were filtered, washed with DCM, and dried to afford the title compound as a light grey solid (34 mg, 32%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.50 (s, 1H) 8.45 (t, J=4.93 Hz, 1H) 8.19 (d, J=5.31 Hz, 1H) 8.06-8.09 (m, 1H) 7.40 (s, 1H) 7.17 (s, 1H) 7.08 (d, J=5.05 Hz, 1H) 5.91 (s, 1H) 5.11 (quin, J=6.57 Hz, 1H) 4.39 (br. s., 1H) 4.38 (br. s., 1H) 3.55-3.62 (m, 4H) 2.53-2.57 (m, 2H) 2.41-2.46 (m, 7H) 2.24 (s, 3H) 2.13 (s, 3H) 1.53-1.61 (m, 2H) 1.47 (s, 3H) 1.46 (s, 3H) 0.93 (t, J=7.33 Hz, 3H); LC-MS (ES) m/z=459.2

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 vessel was sealed
  4. customThe mixture was evaporated
  5. additionDCM was added
  6. customthe contents purified by SiO2 chromatography (eluent: gradient 0 to 80:20:2 DCM/MeOH/NH4OH)
  7. customThe contents were sonicated
  8. customsolids that precipitated
  9. filtrationwere filtered
  10. additionAcetonitrile was added
  11. customthe solids were triturated
  12. filtrationagain filtered
  13. customSolids that precipitated
  14. filtrationwere filtered
  15. washwashed with DCM
  16. customdried

出典と根拠

ORDレコード
ord-b77d48f8482446cb8ec63edeb906045b
出典データセット
uspto-grants-2014_09
特許番号
US08846935B2

反応ノート

読み込み中…