2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → ethyl 5-(6-fluoro-2-methyl-3-((1-methyl-cyclopropyl)amino)quinoxalin-5-yl)-2-methyl-1H-pyrrole-3-carboxylate

HRID 1056289Notes

Reaction equation

HRID 1056289 reaction equation
CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[C:45]1[C:46]([F:61])=[CH:47][CH:48]=[C:49]2[C:54]=1[N:53]=[C:52]([NH:55][C:56]1([CH3:59])[CH2:58][CH2:57]1)[C:51]([CH3:60])=[N:50]2.[CH3:62][C:63]1[NH:64][C:65](B2OC(C)(C)C(C)(C)O2)=[CH:66][C:67]=1[C:68]([O:70][CH2:71][CH3:72])=[O:69]>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:61][C:46]1[C:45]([C:65]2[NH:64][C:63]([CH3:62])=[C:67]([C:68]([O:70][CH2:71][CH3:72])=[O:69])[CH:66]=2)=[C:54]2[C:49](=[CH:48][CH:47]=1)[N:50]=[C:51]([CH3:60])[C:52]([NH:55][C:56]1([CH3:59])[CH2:58][CH2:57]1)=[N:53]2

Participants

8

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 22031701Potassium phosphate, tribasic, monohydrateHCID 897820488-bromo-7-fluoro-3-methyl-N-(1-methylcyclopropyl)quinoxalin-2-amineHCID 89783953ethyl 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-3-carboxylate

Product 1

HCID 89782186ethyl 5-(6-fluoro-2-methyl-3-((1-methyl-cyclopropyl)amino)quinoxalin-5-yl)-2-methyl-1H-pyrrole-3-carboxylateYield 51.1%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of Xphos (Strem Chemicals, 0.169 g, 0.355 mmol), Pd2dba3 (Frontier Scientific, 0.162 g, 0.177 mmol), potassium phosphate tribasic monohydrate (Fluka, 2.450 g, 10.64 mmol), 8-bromo-7-fluoro-3-methyl-N-(1-methylcyclopropyl)quinoxalin-2-amine (610a) (0.880 g, 2.84 mmol), ethyl 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-3-carboxylate (417a) (0.99 g, 3.55 mmol) in dioxane (10.32 mL) and water (3.87 mL) was microwaved to 110° C. for 30 min. Reaction mixture was separated into two biphasic layers. The organic layer was loaded onto a silica gel samplet. Purification by biotage (0-100% EtOAc/hexanes) produced ethyl 5-(6-fluoro-2-methyl-3-((1-methylcyclopropyl)amino)quinoxalin-5-yl)-2-methyl-1H-pyrrole-3-carboxylate (417b) (0.555 g, 1.451 mmol, 41% yield). m/z (ESI, +ve) 383.1 (M+H).

Workup

  1. customwas microwaved to 110° C. for 30 min
  2. customReaction mixture
  3. customwas separated into two biphasic layers
  4. customPurification by biotage (0-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-89710dcbe486437b9ba7d8e1c0cfe44b
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

Loading…