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

HRID 595566노트

반응식

HRID 595566 반응식
[F:1][C:2]1[CH:42]=[CH:41][C:5]([O:6][C:7]2[N:12]=[CH:11][C:10]([C:13]3[O:14][C:15]4[CH:25]=[C:24]([N:26]([CH3:31])[S:27]([CH3:30])(=[O:29])=[O:28])[C:23](B5OC(C)(C)C(C)(C)O5)=[CH:22][C:16]=4[C:17]=3[C:18]([NH:20][CH3:21])=[O:19])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.Cl[C:44]1[CH:45]=[CH:46][C:47]2[O:60][CH2:59][N:50]3[C:51]4[CH:52]=[CH:53][CH:54]=[C:55]([F:58])[C:56]=4[CH:57]=[C:49]3[C:48]=2[N:61]=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.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:58][C:55]1[C:56]2[CH:57]=[C:49]3[C:48]4[N:61]=[C:44]([C:23]5[C:24]([N:26]([CH3:31])[S:27]([CH3:30])(=[O:28])=[O:29])=[CH:25][C:15]6[O:14][C:13]([C:10]7[CH:11]=[N:12][C:7]([O:6][C:5]8[CH:41]=[CH:42][C:2]([F:1])=[CH:3][CH:4]=8)=[CH:8][CH:9]=7)=[C:17]([C:18]([NH:20][CH3:21])=[O:19])[C:16]=6[CH:22]=5)[CH:45]=[CH:46][C:47]=4[O:60][CH2:59][N:50]3[C:51]=2[CH:52]=[CH:53][CH:54]=1

참가 물질

7

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 903338672-(6-(4-fluorophenoxy)pyridin-3-yl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide

생성물 1

HCID 778456625-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(6-(4-fluorophenoxyl)pyridin-3-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide수율 31.4%

시약·촉매·용매 2

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

반응 조건

온도
100 °C

실험 절차

To a stirring mixture of 2-(6-(4-fluorophenoxy)pyridin-3-yl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (50 mg, 0.09 mmol), 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (28 mg, 0.10 mmol) and Na2CO3 (18 mg, 0.17 mmol) in dioxane (0.8 mL) was added X-Phos (5 mg) and Pd2(dba)3 (5 mg) under N2 protection. The mixture was stirred at a pre-heated oil-bath 100° C. for 3 h. The mixture was concentrated and the residue was extracted with EA. The residue was washed with H2O, brine and dried over Na2SO4. After concentrated, the crude product 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-(6-(4-fluorophenoxy)pyridin-3-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (20 mg, yield: 30%). 1H-NMR (CDCl3, 400 MHz) δ 8.70 (d, J=2.0 Hz, 1H), 8.31˜8.34 (m, 1H), 7.91 (s, 1H), 7.62 (s, 1H), 7.44 (s, 2H), 7.15 (s, 2H), 7.04˜7.10 (m, 5H), 6.98 (d, J=8.8 Hz, 1H), 6.76˜6.81 (m, 1H), 5.94 (s, 2H), 5.90 (d, J=8.8 Hz, 1H), 3.30 (s, 3H), 2.96 (d, J=4.8 Hz, 3H), 2.70 (s, 3H). MS (M+H)+: 708.

후처리

  1. concentrationThe mixture was concentrated
  2. extractionthe residue was extracted with EA
  3. washThe residue was washed with H2O, brine
  4. dry with materialdried over Na2SO4
  5. concentrationAfter concentrated
  6. customthe crude product was purified by prep-HPLC

출처 및 근거

ORD 기록
ord-26203b2ac18c458dbb8490064ad3aa33
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242998B2

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