3-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one → 2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-6-ethoxy-2,3-dihydro-1H-isoindol-1-one

HRID 577595Notes

Reaction equation

Br[CH2:2][C:3]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH3:15])=[CH:9][C:4]=1[C:5]([O:7]C)=O.[NH2:16][CH2:17][C:18]1[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=1[CH3:24]>CO>[CH3:24][C:23]1[CH:22]=[C:21]([CH3:25])[NH:20][C:19](=[O:26])[C:18]=1[CH2:17][N:16]1[CH2:2][C:3]2[C:4](=[CH:9][C:10]([O:13][CH2:14][CH3:15])=[CH:11][CH:12]=2)[C:5]1=[O:7]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of methyl 2-(bromomethyl)-5-ethoxybenzoate (134c, 0.636 g, 2.33 mmol) and 3-(aminomethyl)-4,6-dimethylpyridin-2(1H)-one (Cpd V, 0.390 g, 2.56 mmol) in MeOH (20 mL) was added TEA (0.258 g, 2.56 mmol) at room temperature. The resulting mixture was heated at 80° C. for 12 hours. The reaction mixture was concentrated under vacuum to give the crude product, which was purified by column chromatography (CH2Cl2/MeOH=20:1) and then re-crystallized from MeOH (15 mL) to give the title compound (Example 134, 32.6 mg, 4.4%) as a white solid. 1H NMR (400 MHz, methanol-d4) δ 7.39-7.37 (m, 1H), 7.25 (s, 1H), 7.24-7.14 (m, 1H), 6.09 (s, 1H), 4.73 (s, 2H), 4.33 (s, 2H), 4.09-4.07 (q, 2H), 2.30 (s, 3H), 2.24 (s, 3H), 1.43-1.40 (t, 3H); MS 313.0 [M+1].

Workup

concentrationThe reaction mixture was concentrated under vacuum
customto give the crude product, which
customwas purified by column chromatography (CH2Cl2/MeOH=20:1)
customre-crystallized from MeOH (15 mL)

Sources & evidence

ORD record: ord-c3191732292349bdb64ef64fff513320
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040515B2

Reaction notes

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