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Nitrogen → 1-(2-Hydroxy-2-methylpropyl)-N-(4-(5-isoquinolinyl)-3-methylphenyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

HRID 2356353
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HRID 2356353 반응식
[CH:1]1[C:10]2[C:5](=[C:6](B(O)O)[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.Br[C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22]([C:24]2[C:25](=[O:41])[N:26]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[N:27]([CH2:30][C:31]([OH:34])([CH3:33])[CH3:32])[C:28]=2[CH3:29])=[O:23])=[CH:17][C:16]=1[CH3:42].C([O-])(O)=O.[Na+].N#N>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.O1CCOCC1>[OH:34][C:31]([CH3:33])([CH3:32])[CH2:30][N:27]1[C:28]([CH3:29])=[C:24]([C:22]([NH:21][C:18]2[CH:19]=[CH:20][C:15]([C:6]3[CH:7]=[CH:8][CH:9]=[C:10]4[C:5]=3[CH:4]=[CH:3][N:2]=[CH:1]4)=[C:16]([CH3:42])[CH:17]=2)=[O:23])[C:25](=[O:41])[N:26]1[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

HCID 947NitrogenHCID 516892Sodium BicarbonateHCID 599474Isoquinoline-5-boronic acidHCID 59383945N-(4-bromo-3-methylphenyl)-1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

생성물 1

HCID 249989631-(2-Hydroxy-2-methylpropyl)-N-(4-(5-isoquinolinyl)-3-methylphenyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

시약·촉매·용매 2

HCID 178418807HCID 178418807, 화합물촉매HCID 312751,4-Dioxane용매

실험 절차

A sealable tube was charged with PdCl2(dppf)-CH2Cl2 adduct (0.013 g, 0.016 mmol), isoquinolin-5-ylboronic acid (0.057 g, 0.33 mmol), N-(4-bromo-3-methylphenyl)-1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (0.150 g, 0.33 mmol) and 4 mL dioxane. To this mixture, NaHCO3 solution (0.49 ml, 0.98 mmol) was added and the reaction mixture blanket with N2. The vessel was sealed and heated at 80 C for 19 h. The mixture was allowed to cool to rt, filtered through a pad of celite using ethyl acetate as the eluent and the organic layer washed with water, brine, dried over Na2SO4, filtered and evaporated. The mixture was purified via flash chromatography using a mixture of MeOH in EtOAc as the eluent. The title compound was isolated as an off-white solid (80 mg). MS (ESI pos. ion) m/z=507 (MH+). Calc'd mass for C31H30FN4O3: 506.60. 1H NMR (400 MHz, dmso-d6) δ 10.86 (s, 1H), 9.39 (s, 1H), 8.45 (d, J=5.9 Hz, 1H), 8.17 (d, J=8.1 Hz, 1H), 7.74-7.80 (m, 1H), 7.56-7.85 (m, 5H), 7.44-7.50 (m, 1H), 7.37 (d, J=7.7 Hz, 2H), 7.25 (d, J=5.8 Hz, 1H), 7.17 (d, J=8.1 Hz, 1H), 3.31 (s, 2H), 2.82 (s, 3H), 1.95 (s, 3H), 0.98 (s, 6H).

후처리

  1. customThe vessel was sealed
  2. temperatureheated at 80 C for 19 h
  3. filtrationfiltered through a pad of celite
  4. washthe organic layer washed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe mixture was purified via flash chromatography
  9. additiona mixture of MeOH in EtOAc as the eluent

출처 및 근거

ORD 기록
ord-332db742bbcc4f4a93efc74d30daf657
출처 데이터셋
uspto-grants-2010_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07759344B2

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