2-(Di-tert-butylphosphino)biphenyl → 2-{3-[(5-Methyl-7-phenylimidazo[5,1-f][1,2,4]triazin-2-yl)amino]phenyl}-ethanesulfonic acid

HRID 2374955Notes

Reaction equation

Cl.[CH3:2][C:3]1[N:4]=[C:5]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:6]2[C:11]=1[CH:10]=[N:9][C:8]([NH2:12])=[N:7]2.Br[C:20]1[CH:21]=[C:22]([CH2:26][CH2:27][S:28]([OH:31])(=[O:30])=[O:29])[CH:23]=[CH:24][CH:25]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+]>O1CCOCC1.CO>[CH3:2][C:3]1[N:4]=[C:5]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:6]2[C:11]=1[CH:10]=[N:9][C:8]([NH:12][C:20]1[CH:21]=[C:22]([CH2:26][CH2:27][S:28]([OH:31])(=[O:30])=[O:29])[CH:23]=[CH:24][CH:25]=1)=[N:7]2

Participants

Conditions

Temperature: 160 °C

Procedure

To a solution of 5-methyl-7-phenylimidazo[5,1-f][1,2,4]triazin-2-amine hydrochloride (28 mg, 0.107 mmol) in 1,4-dioxane (0.8 mL) was added 2-(3-bromophenyl)ethanesulfonic acid (28.25 mg, 0.107 mmol), 2-(dit-butylphosphino)biphenyl (9.6 mg, 0.032 mmol), Tris(dibenzylidineacetone)-dipalladium (0) (9.8 mg, 0.011 mmol) and sodium t-butoxide (23.65 mg, 0.246 mmol). In a sealed reaction vessel, the mixture was heated with microwave radiation at 160° C. for 13 minutes. After cooling to room temperature, methanol (5 mL) and silica gel (1.0 g) were added to the reaction mixture, followed by evaporation of the volatiles under reduced pressure. The pre-adsorbed solids were loaded into a solid loading cartridge and subjected to isocratic elution using ethyl acetate:hexanes (50:50) followed by ethyl acetate:methanol (80:20) using a Biotage silica gel cartridge (8.0 g). The appropriate fractions were combined and concentrated under reduced pressure to give 2-{3-[(5-methyl-7-phenylimidazo[5,1-f][1,2,4]triazin-2-yl)amino]phenyl}-ethanesulfonic acid (0.029 g) as a yellow solid. 1H NMR (DMSO-d6): δ9.73 (s, 1H), 9.23 (s, 1H), 8.42 (d, J=7.5 Hz, 2H), 7.74 (s, 1H), 7.63 (dd, J=7.70 Hz, 2H), 7.49-7.07 (m, 3H), 6.86 (d, J=7.3 Hz, 1H), 2.94-2.82 (m, 2H), 2.71-2.62 (m, 2H), 2.52 (s, 3H). MS m/z 410 (M+1).

Workup

customIn a sealed reaction vessel
temperatureAfter cooling to room temperature
customfollowed by evaporation of the volatiles under reduced pressure
washsubjected to isocratic elution
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-ba03ae1658ae44b890df566ce94fbd58
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07462614B2

Reaction notes

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