HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

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

HRID 595576
Notes
Print preview

Reaction equation

HRID 595576 reaction equation
[N:1]1([C:6]2[O:7][C:8]3[CH:18]=[C:17]([N:19]([CH3:24])[S:20]([CH3:23])(=[O:22])=[O:21])[C:16](B4OC(C)(C)C(C)(C)O4)=[CH:15][C:9]=3[C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[CH:5]=[CH:4][N:3]=[CH:2]1.Cl[C:35]1[CH:36]=[CH:37][C:38]2[O:51][CH2:50][N:41]3[C:42]4[CH:43]=[CH:44][CH:45]=[C:46]([F:49])[C:47]=4[CH:48]=[C:40]3[C:39]=2[N:52]=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:49][C:46]1[C:47]2[CH:48]=[C:40]3[C:39]4[N:52]=[C:35]([C:16]5[C:17]([N:19]([CH3:24])[S:20]([CH3:23])(=[O:22])=[O:21])=[CH:18][C:8]6[O:7][C:6]([N:1]7[CH:5]=[CH:4][N:3]=[CH:2]7)=[C:10]([C:11]([NH:13][CH3:14])=[O:12])[C:9]=6[CH:15]=5)[CH:36]=[CH:37][C:38]=4[O:51][CH2:50][N:41]3[C:42]=2[CH:43]=[CH:44][CH:45]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 867283052-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indoleHCID 903336142-(1H-imidazol-1-yl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide

Product 1

HCID 77845758
5-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(1H-imidazol-1-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide
Yield 40%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 2-(1H-imidazol-1-yl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (60 mg, 0.13 mmol), 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (42 mg, 0.15 mmol) and K2CO3 (26 mg, 0.19 mmol) in 1,4-dioxane (1 mL) and water (0.01 mL) were added X-Phos (10 mg) and Pd2(dba)3 (10 mg) under nitrogen. The mixture was heated at 110° C. for 3 hours and filtered through the celite pad. The filtrate was extracted with EtOAc and the combined organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by prep-HPLC to give 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(1H-imidazol-1-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (30 mg, yield: 40%). 1H-NMR (400 MHz, CDCl3) δ 8.36 (s, 1H), 8.03 (s, 1H), 7.73 (s, 1H), 7.68 (s, 1H), 7.52 (s, 2H), 7.20˜7.25 (m, 3H), 7.12 (d, J=8.4 Hz, 1H), 6.84˜6.88 (m, 1H), 6.02 (s, 2H), 5.93 (d, J=4.8 Hz, 1H), 3.35 (s, 3H), 3.02 (d, J=4.8 Hz, 3H), 2.78 (s, 3H). MS (M+H)+: 587.

Workup

  1. filtrationfiltered through the celite pad
  2. extractionThe filtrate was extracted with EtOAc
  3. washthe combined organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by prep-HPLC

Sources & evidence

ORD record
ord-69ac8263a5044e4a93128946c6ef7a86
Source dataset
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09242998B2

Reaction notes

Loading…

On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes