Potassium Phosphate, Tribasic → 5-(10-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595660노트

반응식

HRID 595660 반응식
Cl[C:2]1[CH:11]=[CH:10][C:9]2[CH2:8][CH2:7][N:6]3[C:12]4[CH:13]=[CH:14][C:15]([F:19])=[CH:16][C:17]=4[CH:18]=[C:5]3[C:4]=2[N:3]=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[O:28][C:29]3[CH:39]=[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])[C:37](B4OC(C)(C)C(C)(C)O4)=[CH:36][C:30]=3[C:31]=2[C:32]([NH:34][CH3:35])=[O:33])=[CH:23][CH:22]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:19][C:15]1[CH:14]=[CH:13][C:12]2[N:6]3[CH2:7][CH2:8][C:9]4[CH:10]=[CH:11][C:2]([C:37]5[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])=[CH:39][C:29]6[O:28][C:27]([C:24]7[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=7)=[C:31]([C:32]([NH:34][CH3:35])=[O:33])[C:30]=6[CH:36]=5)=[N:3][C:4]=4[C:5]3=[CH:18][C:17]=2[CH:16]=1

참가 물질

7

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 903334282-Chloro-10-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine

생성물 1

HCID 778456665-(10-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide수율 61.5%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

To a degassed solution of 2-chloro-10-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (50 mg, 0.18 mmol) and 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (80 mg, 0.16 mmol) in 1,4-dioxane (5 mL), Pd2(dba)3 (10 mg), X-Phos (10 mg) and K3PO4 (100 mg, 0.38 mmol) were added under N2. After heated to 100° C. for 1 hour, the reaction mixture was cooled to RT, filtered and washed with EtOAc. The filtrate was washed with H2O, brine, dried over Na2SO4. After concentrated, the residue was purified by prep-HPLC to give the product (60 mg, yield: 61.5%). 1H-NMR (CDCl3, 400 MHz) δ 7.99 (s, 1H), 7.92˜7.98 (m, 2H), 7.65˜7.67 (m, 2H), 7.43 (d, J=7.6 Hz, 1H), 7.28˜7.32 (m, 2H), 7.15˜7.24 (m, 3H), 6.98˜7.03 (m, 1H), 6.05 (br s, 1H), 4.31 (t, J=6.4 Hz, 2H), 3.36 (s, 3H), 3.30 (t, J=6.4 Hz, 2H), 2.97 (d, J=4.8 Hz, 3H), 2.68 (s, 3H). MS (M+H)+: 613.

후처리

  1. temperaturethe reaction mixture was cooled to RT
  2. filtrationfiltered
  3. washwashed with EtOAc
  4. washThe filtrate was washed with H2O, brine
  5. dry with materialdried over Na2SO4
  6. concentrationAfter concentrated
  7. customthe residue was purified by prep-HPLC

출처 및 근거

ORD 기록
ord-88338c357b75435b93df5d67baca4d9f
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09243002B2

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