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 595566Notes

Reaction equation

HRID 595566 reaction equation
[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

Participants

7

Reactant 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

Product 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-carboxamideYield 31.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-26203b2ac18c458dbb8490064ad3aa33
Source dataset
uspto-grants-2016_01
Patent number
US09242998B2

Reaction notes

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