4-Fluorophenylboronic acid → N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(4-fluorophenyl)-1-isopropyl-3-methyl-1H-indazole-4-carboxamide

HRID 85489노트

반응식

HRID 85489 반응식
Br[C:2]1[CH:3]=[C:4]([C:15]([NH:17][CH2:18][C:19]2[C:20](=[O:27])[NH:21][C:22]([CH3:26])=[CH:23][C:24]=2[CH3:25])=[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.[F:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=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>[CH3:25][C:24]1[CH:23]=[C:22]([CH3:26])[NH:21][C:20](=[O:27])[C:19]=1[CH2:18][NH:17][C:15]([C:4]1[C:5]2[C:6]([CH3:14])=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=[C:2]([C:32]2[CH:33]=[CH:34][C:29]([F:28])=[CH:30][CH:31]=2)[CH:3]=1)=[O:16]

참가 물질

6

반응물 3

HCID 2856454-Fluorophenylboronic acidHCID 516892Sodium BicarbonateHCID 545962226-bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indazole-4-carboxamide

생성물 1

HCID 54596301N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(4-fluorophenyl)-1-isopropyl-3-methyl-1H-indazole-4-carboxamide수율 77.9%

시약·촉매·용매 2

HCID 178418807HCID 178418807, 화합물촉매HCID 218864351,4-Dioxane--water (1/1)용매

반응 조건

온도
100 °C

실험 절차

In a 25 mL sealable tube under nitrogen were combined 6-bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-indazole-4-carboxamide (90 mg, 0.21 mmol), (4-fluorophenyl)boronic acid (43.8 mg, 0.31 mmol) in dioxane/water (3 mL:1 mL). PdCl2(dppf)-CH2Cl2 adduct (5.11 mg, 0.006 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (52.6 mg, 0.63 mmol) was added, the vessel was sealed, and the insoluble mixture was heated in a microwave at 100° C. for 20 min. The mixture was evaporated, DCM/MeOH (1:1) was added, the contents pre-absorbed on silica gel and 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 mixture was sonicated, and the solids that precipitated were filtered and dried to afford the title compound as a white solid (73 mg, 77%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.50 (s, 1H) 8.46 (t, J=5.05 Hz, 1H) 7.94 (d, J=1.26 Hz, 1H) 7.83-7.88 (m, 2H) 7.31-7.36 (m, 3H) 5.88 (s, 1H) 5.06 (quin, J=6.63 Hz, 1H) 4.38 (s, 1H) 4.36 (s, 1H) 2.43 (s, 3H) 2.24 (s, 3H) 2.12 (s, 3H) 1.47 (s, 3H) 1.45 (s, 3H). LC-MS (ES) m/z=446.9

후처리

  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/MeOH (1:1) was added
  6. customthe contents pre-absorbed on silica gel
  7. custompurified by SiO2 chromatography (eluent: gradient 0 to 80:20:2 DCM/MeOH/NH4OH)
  8. customThe mixture was sonicated
  9. customthe solids that precipitated
  10. filtrationwere filtered
  11. customdried

출처 및 근거

ORD 기록
ord-b5679d85014a4ad8a1bbca57885935ae
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846935B2

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