1,4-Dioxane → 1-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(4-((dimethylamino)methyl)phenyl)-1H-indazole-4-carboxamide

HRID 85466

反応式

HRID 85466 の反応式
Br[C:2]1[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]2[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=2[CH3:26])=[O:17])[C:5]2[CH:6]=[N:7][N:8]([CH:11]3[CH2:15][CH2:14][CH2:13][CH2:12]3)[C:9]=2[CH:10]=1.[CH3:29][N:30]([CH3:47])[CH2:31][C:32]1[CH:37]=[CH:36][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][CH:33]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>CCOC(C)=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.O>[CH:11]1([N:8]2[C:9]3[CH:10]=[C:2]([C:35]4[CH:36]=[CH:37][C:32]([CH2:31][N:30]([CH3:47])[CH3:29])=[CH:33][CH:34]=4)[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]4[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=4[CH3:26])=[O:17])[C:5]=3[CH:6]=[N:7]2)[CH2:15][CH2:14][CH2:13][CH2:12]1

参加物

8

反応物 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 34604594-((N,N-Dimethylamino)methyl)phenylboronic acid pinacol esterHCID 545970746-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-1H-indazole-4-carboxamide

生成物 1

HCID 545972301-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(4-((dimethylamino)methyl)phenyl)-1H-indazole-4-carboxamide

試薬・触媒・溶媒 3

HCID 178418807HCID 178418807、化合物触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

To a sealed tube were added 6-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (0.10 g, 0.226 mmol), N,N-dimethyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanamine (0.081 g, 0.271 mmol), and potassium phosphate (tribasic) (0.192 g, 0.902 mmol) followed by 1,4-Dioxane (2.0 mL) and water (0.5 mL). The suspension was stirred with degassing under N2 for 10 min, followed by addition of PdCl2(dppf)-CH2Cl2 adduct (0.018 g, 0.023 mmol). The reaction vessel was sealed and stirred with heating at 100° C. (heat block) for 2 h. The contents were allowed to stir with cooling to RT overnight. The mixture was diluted with EtOAc followed by addition of silica gel. The mixture was concentrated in vacuo and the obtained solid purified by silica gel chromatography (dry loaded, eluent: 8-95% gradient of chloroform (containing 10% 2M Ammonia in Methanol) and DCM. The collected product was concentrated from DCM/MTBE and then dried in vacuum oven for 16 h. The title compound was collected as an off-white solid (45 mg, 39%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.65-1.76 (m, 2H), 1.83-1.94 (m, 2H), 1.97-2.07 (m, 2H), 2.09-2.19 (m, 11H), 2.21 (s, 3H), 3.44 (s, 2H), 4.39 (d, J=4.80 Hz, 2H), 5.34 (quin, J=7.14 Hz, 1H), 5.88 (s, 1H), 7.41 (m, J=8.34 Hz, 2H), 7.81 (m, J=8.08 Hz, 2H), 7.87 (d, J=1.01 Hz, 1H), 8.12 (s, 1H), 8.36 (s, 1H), 8.65 (t, J=4.93 Hz, 1H), 11.53 (s, 1H); LC-MS (ES) m/z=498.3 [M+H]+

後処理

  1. customwith degassing under N2 for 10 min
  2. customThe reaction vessel was sealed
  3. stirringstirred
  4. temperature(heat block) for 2 h
  5. stirringto stir
  6. temperaturewith cooling to RT overnight
  7. additionfollowed by addition of silica gel
  8. concentrationThe mixture was concentrated in vacuo
  9. customthe obtained solid purified by silica gel chromatography (
  10. customdry
  11. concentrationThe collected product was concentrated from DCM/MTBE
  12. customdried in vacuum oven for 16 h
  13. customThe title compound was collected as an off-white solid (45 mg, 39%)

出典と根拠

ORDレコード
ord-aae989e2c4064cfc954da92eec1f1922
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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