Dichloromethane → HCID 86728246, compound

HRID 1776840Notes

Reaction equation

HRID 1776840 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[O:19][CH2:18][N:8]3[C:9]4[CH:10]=[CH:11][CH:12]=[C:13]([CH:16]=[O:17])[C:14]=4[CH:15]=[C:7]3[C:6]=2[N:20]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[O:29][C:30]3[CH:40]=[C:39]([N:41]([CH3:46])[S:42]([CH3:45])(=[O:44])=[O:43])[C:38](B4OC(C)(C)C(C)(C)O4)=[CH:37][C:31]=3[C:32]=2[C:33]([NH:35][CH3:36])=[O:34])=[CH:24][CH:23]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.ClCCl>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].CO>[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[O:29][C:30]3[CH:40]=[C:39]([N:41]([CH3:46])[S:42]([CH3:45])(=[O:43])=[O:44])[C:38]([C:2]4[CH:3]=[CH:4][C:5]5[O:19][CH2:18][N:8]6[C:9]7[CH:10]=[CH:11][CH:12]=[C:13]([CH:16]=[O:17])[C:14]=7[CH:15]=[C:7]6[C:6]=5[N:20]=4)=[CH:37][C:31]=3[C:32]=2[C:33]([NH:35][CH3:36])=[O:34])=[CH:24][CH:23]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 86728244HCID 86728244, compound

Product 1

HCID 86728246HCID 86728246, compoundYield 80%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-chloro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole-11-carbaldehyde (31 mg, 0.11 mmol), 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (50 mg, 0.10 mmol) and K3PO4.3H2O (53 mg, 0.19 mmol) in 1,4-dioxane (1 mL) and water (0.2 mL) was added X-Phos (5 mg) and Pd2(dba)3 (5 mg) under nitrogen. The mixture was heated at 100° C. for 16 hours, and then filtered through the celite pad. The filtrate was extracted with EtOAc, then the combined organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuo to provide the 2-(4-fluorophenyl)-5-(11-formyl-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (50 mg, yield: 80%) by the prep-TLC (dichloromethane:MeOH=30:1). MS (M+H)+: 625.

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

Sources & evidence

ORD record
ord-70e1a1f68ae547ed94b4f5dd39c17f7b
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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