2-tert-Butyl-5-(2-methyl-3-(4-methyl-6-(4-(1-methyl-3-oxopiperazin-2-yl)phenylamino)-5-oxo-4,5-dihydropyrazin-2-yl)phenyl)-4H-thieno[2,3-c]pyrrol-6(5H)-one → 5-(Dimethylamino)-2-(2-(hydroxymethyl)-3-(1-methyl-6-oxo-5-(pyrimidin-4-ylamino)-1,6-dihydropyridin-3-yl)phenyl)isoindolin-1-one

Participants

Role	Name	HCID	Charge
Reactant	2-tert-Butyl-5-(2-methyl-3-(4-methyl-6-(4-(1-methyl-3-oxopiperazin-2-yl)phenylamino)-5-oxo-4,5-dihydropyrazin-2-yl)phenyl)-4H-thieno[2,3-c]pyrrol-6(5H)-one	HCID 56928442	—
Reactant	5-bromo-1-methyl-3-(pyrimidin-4-ylamino)pyridin-2(1H)-one	HCID 58044094	—
Reactant	2-(5-(Dimethylamino)-1-oxoisoindolin-2-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl Acetate	HCID 86699872	—
Product	5-(Dimethylamino)-2-(2-(hydroxymethyl)-3-(1-methyl-6-oxo-5-(pyrimidin-4-ylamino)-1,6-dihydropyridin-3-yl)phenyl)isoindolin-1-one	HCID 56928860	33.6%

Reaction Steps

Using the same general procedure as described for the preparation of 104, reaction of 123e (400 mg, 0.890 mmol) with 107a (207 mg, 0.740 mmol) followed by a hydrolysis gave a 28% yield (120 mg) of 124 as a white solid: mp 206-208° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.17 (s, 1H), 8.73 (d, 1H, J=2.0 Hz), 8.65 (s, 1H), 8.30 (d, 1H, J=6.0 Hz), 7.57 (d, 1H, J=8.5 Hz), 7.55 (d, 1H, J=2.5 Hz), 7.49 (t, 1H, J=2.5 Hz), 7.43 (dd, 1H, J=8.0, 1.5 Hz), 7.37 (dd, 1H, J=8.0, 1.5 Hz), 7.31 (dd, 1H, J=6.0, 1.5 Hz), 6.88-6.85 (m, 2H), 4.94 (t, 1H, J=4.5 Hz), 4.86 (s, 2H), 4.32 (d, 2H, J=4.5 Hz), 3.61 (s, 3H), 3.04 (s, 6H); MS (ESI+) m/z 483.2 (M+H).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09249123B2
Source dataset	uspto-grants-2016_02
ORD ID	ord-0e4cdfa5867142b89a41ebef002bad46
Source note	uspto-grants-2016_02