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Sodium Bicarbonate → 1-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-6-(2-methylpyrimidin-5-yl)-1H-indazole-4-carboxamide

HRID 1476394
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HRID 1476394 반응식
Br[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:28])[NH:20][C:21]([CH3:27])=[CH:22][C:23]=2[CH2:24][CH2:25][CH3:26])=[O:15])[C:5]2[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.[CH3:29][C:30]1[N:35]=[CH:34][C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][N:31]=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:33]3[CH:32]=[N:31][C:30]([CH3:29])=[N:35][CH:34]=3)[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]3[C:19](=[O:28])[NH:20][C:21]([CH3:27])=[CH:22][C:23]=3[CH2:24][CH2:25][CH3:26])=[O:15])[C:5]=2[CH:6]=[N:7]1)([CH3:13])[CH3:12]
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참가 물질

6

반응물 3

HCID 516892Sodium BicarbonateHCID 457872822-Methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidineHCID 674653266-bromo-1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide

생성물 1

HCID 545966921-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-6-(2-methylpyrimidin-5-yl)-1H-indazole-4-carboxamide수율 42%

시약·촉매·용매 2

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

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온도
110 °C

실험 절차

In a 25 mL sealable tube under nitrogen were combined 6-bromo-1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (100 mg, 0.23 mmol), 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (64.2 mg, 0.29 mmol) in dioxane/water (3 mL:1 mL). PdCl2(dppf)-CH2Cl2 adduct (9.2 mg, 0.011 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (56.6 mg, 0.67 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/MeOH (1:1) was added, and 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 acetonitrile along with a few drops of EtOH and some hexanes. The contents were sonicated, and solids that precipitated were filtered and dried to afford the title compound as an off-white solid (44 mg, 42%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.55 (s, 1H) 9.21 (s, 2H) 8.63 (t, J=4.80 Hz, 1H) 8.43 (s, 1H) 8.32 (s, 1H) 7.94-7.96 (m, 1H) 5.92 (s, 1H) 5.17 (quin, J=6.63 Hz, 1H) 4.43 (br. s., 1H) 4.42 (br. s., 1H) 2.69 (s, 3H) 2.52-2.56 (m, 2H) 2.14 (s, 3H) 1.49-1.55 (m, 8H) 0.88 (t, J=7.33 Hz, 3H); LC-MS (ES) m/z=459.2

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 contents were sonicated
  9. customsolids that precipitated
  10. filtrationwere filtered
  11. customdried

출처 및 근거

ORD 기록
ord-d64977c73935455f8355078d64ddca6e
출처 데이터셋
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09018382B2

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