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Sodium Carbonate → 5-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(2-methoxypyridin-4-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595545
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HRID 595545 반응식
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]2[O:10][C:11]3[CH:21]=[C:20]([N:22]([CH3:27])[S:23]([CH3:26])(=[O:25])=[O:24])[C:19](B4OC(C)(C)C(C)(C)O4)=[CH:18][C:12]=3[C:13]=2[C:14]([NH:16][CH3:17])=[O:15])[CH:6]=[CH:5][N:4]=1.Cl[C:38]1[CH:39]=[CH:40][C:41]2[O:54][CH2:53][N:44]3[C:45]4[CH:46]=[CH:47][CH:48]=[C:49]([F:52])[C:50]=4[CH:51]=[C:43]3[C:42]=2[N:55]=1.C([O-])([O-])=O.[Na+].[Na+].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:52][C:49]1[C:50]2[CH:51]=[C:43]3[C:42]4[N:55]=[C:38]([C:19]5[C:20]([N:22]([CH3:27])[S:23]([CH3:26])(=[O:24])=[O:25])=[CH:21][C:11]6[O:10][C:9]([C:7]7[CH:6]=[CH:5][N:4]=[C:3]([O:2][CH3:1])[CH:8]=7)=[C:13]([C:14]([NH:16][CH3:17])=[O:15])[C:12]=6[CH:18]=5)[CH:39]=[CH:40][C:41]=4[O:54][CH2:53][N:44]3[C:45]=2[CH:46]=[CH:47][CH:48]=1
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 4

HCID 10340Sodium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 867283052-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indoleHCID 903335752-(2-methoxypyridin-4-yl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide

생성물 1

HCID 77845113
5-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(2-methoxypyridin-4-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide
수율 48%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

To a degassed solution of 2-(2-methoxypyridin-4-yl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (60 mg, 0.12 mmol), 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (35 mg, 0.13 mmol) and Na2CO3 (25 mg, 0.23 mmol) in dioxane (1.5 mL) and H2O (0.1 mL) was added Pd2(dba)3 (3 mg) and X-Phos (3 mg) under N2. Then the mixture was stirred at 100° C. for 2 hours. The reaction mixture was cooled to RT and filtered. The filtrate was washed with H2O and dried over Na2SO4. After concentrated, the residue was purified by prep-HPLC to give the product of 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(2-methoxypyridin-4-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (35 mg, yield: 48%). 1H-NMR (CDCl3, 400 MHz) δ 8.29 (s, 1H), 8.28 (s, 1H), 7.98 (s, 1H), 7.69 (s, 2H), 7.40˜7.49 (m, 1H), 7.30 (s, 1H), 7.19˜7.24 (m, 2H), 7.10˜7.18 (m, 1H), 6.82˜6.87 (m, 1H), 6.11 (s, 1H), 5.99 (s, 2H), 3.99 (s, 3H), 3.36 (s, 3H), 3.04 (d, J=4.8 Hz, 3H), 2.75 (s, 3H). MS (M+H)+: 628.

후처리

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

출처 및 근거

ORD 기록
ord-14be6b013d1c4309a353505d669e338c
출처 데이터셋
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09242998B2

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