Potassium Phosphate, Tribasic → HCID 89783629, compound

HRID 1056315Notes

Reaction equation

HRID 1056315 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:12][C:13]([CH3:16])([CH3:15])[CH3:14])[C:8]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[N:7]2.CC1(C)C(C)(C)OB([C:31]2[NH:39][C:38]3[CH2:37][CH2:36][NH:35][C:34](=[O:40])[C:33]=3[CH:32]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>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.C(Cl)Cl>[C:13]([NH:12][C:9]1[C:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[N:7][C:6]2[C:11]([N:10]=1)=[C:2]([C:31]1[NH:39][C:38]3[CH2:37][CH2:36][NH:35][C:34](=[O:40])[C:33]=3[CH:32]=1)[CH:3]=[CH:4][CH:5]=2)([CH3:16])([CH3:15])[CH3:14]

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 897834962-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-YL)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-C]pyridin-4-oneHCID 89784607HCID 89784607, compound

Product 1

HCID 89783629HCID 89783629, compoundYield 52.4%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 8-bromo-N-(tert-butyl)-3-phenylquinoxalin-2-amine (83.0 mg, 0.233 mmol), 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 609; 172 mg, 0.466 mmol), K3PO4 (148 mg, 0.699 mmol), dicyclohexyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (XPhos; Strem Chemicals, Inc.; 11.11 mg, 0.023 mmol), and Pd2dba3 (Aldrich; 10.67 mg, 0.012 mmol) in a mixture of 1,4-dioxane (2.0 mL) and water (0.400 mL) was stirred under argon at 100° C. for 1 h. The reaction mixture was then concentrated onto silica gel and chromatographically purified (silica gel, 50-100% EtOAc/hexanes, then 0-10% MeOH/DCM) to provide 2-(3-(tert-butylamino)-2-phenylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (50.0 mg, 0.122 mmol, 52% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 12.72 (1H, br. s.), 7.99 (1H, dd, J=7.6, 1.4 Hz), 7.77 (1H, dd, J=8.1, 1.3 Hz), 7.71 (2H, dd, J=7.8, 1.6 Hz), 7.53-7.62 (3H, m), 7.41 (1H, t, J=7.8 Hz), 7.13 (1H, d, J=2.2 Hz), 5.98-6.21 (1H, m), 5.36 (1H, s), 3.71 (2H, t, J=6.9 Hz), 3.03 (2H, t, J=7.0 Hz), 1.59 (9H, s). m/z (ESI, +ve) 412.0 (M+H)+.

Workup

  1. concentrationThe reaction mixture was then concentrated onto silica gel
  2. customchromatographically purified (silica gel, 50-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-0f2266f0896541328c758ccbaf7fe733
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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