Potassium Carbonate → 5-(11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-N-methyl-2-(4-methyl-2-oxopyridin-1 (2H)-yl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595662노트

반응식

HRID 595662 반응식
[CH3:1][NH:2][C:3]([C:5]1[C:9]2[CH:10]=[C:11](B3OC(C)(C)C(C)(C)O3)[C:12]([N:14]([CH3:19])[S:15]([CH3:18])(=[O:17])=[O:16])=[CH:13][C:8]=2[O:7][C:6]=1[N:29]1[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][C:30]1=[O:36])=[O:4].Cl[C:38]1[CH:47]=[CH:46][C:45]2[CH2:44][CH2:43][N:42]3[C:48]4[CH:49]=[CH:50][CH:51]=[C:52]([F:55])[C:53]=4[CH:54]=[C:41]3[C:40]=2[N:39]=1.C([O-])([O-])=O.[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.O.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:55][C:52]1[C:53]2[CH:54]=[C:41]3[C:40]4[N:39]=[C:38]([C:11]5[C:12]([N:14]([CH3:19])[S:15]([CH3:18])(=[O:16])=[O:17])=[CH:13][C:8]6[O:7][C:6]([N:29]7[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][C:30]7=[O:36])=[C:5]([C:3]([NH:2][CH3:1])=[O:4])[C:9]=6[CH:10]=5)[CH:47]=[CH:46][C:45]=4[CH2:44][CH2:43][N:42]3[C:48]=2[CH:49]=[CH:50][CH:51]=1

참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 90333625N-methyl-2-(4-methyl-2-oxopyridin-1 (2H)-yl)-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 903336312-Chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine

생성물 1

HCID 778451105-(11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-N-methyl-2-(4-methyl-2-oxopyridin-1 (2H)-yl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide수율 25.2%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 218864351,4-Dioxane--water (1/1)용매

반응 조건

온도
80 °C

실험 절차

To a mixture of N-methyl-2-(4-methyl-2-oxopyridin-1 (2H)-yl)-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (100 mg, 0.19 mmol), 2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (63 mg, 0.23 mmol) and K2CO3 (54 mg, 0.39 mmol) in 1,4-dioxane/H2O (3 mL/0.1 mL) were added X-Phos (10 mg) and Pd2(dba)3 (10 mg) under N2. The reaction mixture was stirred at 80° C. for 5 hours and concentrated in vacuo to remove 1,4-dioxane. The reaction mixture was extracted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by prep-HPLC to give the product (30 mg, yield: 24%). 1H-NMR (CDCl3, 400 MHz) δ 8.17 (s, 1H), 7.83˜7.85 (m, 1H), 7.66˜7.68 (m, 2H), 7.44 (d, J=8.0 Hz, 1H), 7.26˜7.18 (m, 2H), 7.14˜7.18 (m, 2H), 6.77˜6.81 (m, 1H), 6.53 (s, 1H), 6.29 (d, J=8.0 Hz, 1H), 4.34 (t, J=6.4 Hz, 2H), 3.40 (s, 3H), 3.31 (t, J=6.4 Hz, 2H), 2.90 (d, J=4.8 Hz, 3H), 2.61 (s, 3H), 2.32 (s, 3H). MS (M+H)+: 626.

후처리

  1. concentrationconcentrated in vacuo
  2. customto remove 1,4-dioxane
  3. extractionThe reaction mixture was extracted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by prep-HPLC

출처 및 근거

ORD 기록
ord-520e1d8559d34964bfa4b0d0d5b4c4e5
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09243002B2

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