5-Bromo-1-methyl-3-(4-morpholinophenylamino)pyrazin-2(1H)-one → 5-tert-Butyl-2-(2-(hydroxymethyl)-3-(4-methyl-6-(4-morpholinophenylamino)-5-oxo-4,5-dihydropyrazin-2-yl)phenyl)isoindolin-1-one

Participants

Role	Name	HCID	Charge
Reactant	5-Bromo-1-methyl-3-(4-morpholinophenylamino)pyrazin-2(1H)-one	HCID 66613402	—
Reactant	2-(5-tert-Butyl-1-oxoisoindolin-2-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl Acetate	HCID 86697936	—
Product	5-tert-Butyl-2-(2-(hydroxymethyl)-3-(4-methyl-6-(4-morpholinophenylamino)-5-oxo-4,5-dihydropyrazin-2-yl)phenyl)isoindolin-1-one	HCID 56928446	47%

Reaction Steps

Using the same general procedure as Example 105, reaction of 108a (296 mg, 0.810 mmol) with 103f (413 mg, 0.891 mmol) afforded 108 in 47% yield (205 mg) as an amorphous yellow solid: mp 225-227° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.08 (s, 1H), 7.83 (d, J=9.0 Hz, 2H), 7.73 (d, J=8.5 Hz, 2H), 7.62 (dd, J=8.0, 1.5 Hz, 1H), 7.58 (dd, J=8.0, 1.5 Hz, 1H), 7.50 (t, J=7.5 Hz, 1H), 7.42 (dd, J=8.0, 1.0 Hz, 1H), 7.34 (s, 1H), 6.89 (d, J=9.0 Hz, 2H), 4.92 (s, 2H), 4.83 (t, J=5.0 Hz, 1H), 4.43 (d, J=5.0 Hz, 2H), 3.72 (t, J=5.5 Hz, 4H), 3.54 (s, 3H), 3.03 (t, J=5.5 Hz, 4H), 1.37 (s, 9H); MS (ESI+) m/z 580.3 (M+H).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09249123B2
Source dataset	uspto-grants-2016_02
ORD ID	ord-06856c405daa4abd9c9241da87cbf0ac
Source note	uspto-grants-2016_02