2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one

HRID 1056166Notes

Reaction equation

[C:1]([NH:5][C:6]1[C:15]([CH3:16])=[N:14][C:13]2[C:8](=[C:9](B3OC(C)(C)C(C)(C)O3)[CH:10]=[CH:11][CH:12]=2)[N:7]=1)([CH3:4])([CH3:3])[CH3:2].Br[C:27]1[NH:36][C:35]2[CH2:34][CH2:33][CH2:32][NH:31][C:30](=[O:37])[C:29]=2[CH:28]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CO.C(Cl)Cl>O1CCOCC1.O.C(Cl)Cl.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]>[C:1]([NH:5][C:6]1[C:15]([CH3:16])=[N:14][C:13]2[C:8]([N:7]=1)=[C:9]([C:27]1[NH:36][C:35]3[CH2:34][CH2:33][CH2:32][NH:31][C:30](=[O:37])[C:29]=3[CH:28]=1)[CH:10]=[CH:11][CH:12]=2)([CH3:2])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: 105 °C

Procedure

A mixture of N-(tert-butyl)-3-methyl-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoxalin-2-amine (174b) (341 mg, 0.66 mmol), 2-bromo-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one (305b) (84.0 mg, 0.37 mmol), K2PO4 (420 mg, 1.98 mmol), X-Phos (Strem Chemicals, Inc., 17.5 mg, 0.037 mmol), and Pd2dba3 (Aldrich, 16.8 mg, 0.018 mmol) in a mixture of dioxane (3.0 mL) and water (0.60 mL) was stirred under argon at 105° C. for 1.5 h. The reaction mixture was subsequently diluted with DCM (10 mL) and concentrated onto silica gel. Chromatographic purification (silica gel, 0-100% EtOAc/hexanes, then 0-10% MeOH/DCM) furnished 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one (128 mg, 0.35 mmol, 96% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.77 (1H, br. s.), 7.83 (1H, dd, J=7.4, 1.0 Hz), 7.56 (1H, dd, J=7.8, 1.0 Hz), 7.32 (2H, t, J=7.7 Hz), 7.09 (1H, d, J=2.7 Hz), 6.01 (1H, s), 3.21 (2H, dd, J=8.5, 4.6 Hz), 3.02 (2H, t, J=6.5 Hz), 2.55 (3H, s), 1.92-2.01 (2H, m), 1.58 (9H, s). m/z (ESI, +ve) 364.2 (M+H)+.

Workup

concentrationconcentrated onto silica gel
customChromatographic purification (silica gel, 0-100% EtOAc/hexanes

Sources & evidence

ORD record: ord-404de2ff668d4900869377f0d4a6c212
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394297B2

Reaction notes

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