Water → 5-Methyl-7-pyridin-3-yl-2-(2-[1,2,4]triazolo[1,5-a]pyridin-2-yl-ethyl)-3,5-dihydro-2H-pyrrolo[3,4-c]pyridine-1,6-dione

HRID 1752630Notes

Reaction equation

C([O-])([O-])=O.[K+].[K+].Cl[C:8]1[C:13](=[O:14])[N:12]([CH3:15])[CH:11]=[C:10]2[CH2:16][N:17]([CH2:20][CH2:21][C:22]3[N:30]=[C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][N:24]4[N:23]=3)[C:18](=[O:19])[C:9]=12.[N:31]1[CH:36]=[CH:35][CH:34]=[C:33](B(O)O)[CH:32]=1.O>CN(C=O)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:15][N:12]1[C:13](=[O:14])[C:8]([C:33]2[CH:32]=[N:31][CH:36]=[CH:35][CH:34]=2)=[C:9]2[C:18](=[O:19])[N:17]([CH2:20][CH2:21][C:22]3[N:30]=[C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][N:24]4[N:23]=3)[CH2:16][C:10]2=[CH:11]1

Participants

Conditions

Temperature: 120 °C

Procedure

K2CO3 (60.3 mg, 0.436 mmol) and bis(triphenylphosphine) palladium(II) dichloride (10.21 mg, 0.015 mmol) were each rapidly added in sequence to a suspension of 7-chloro-5-methyl-2-(2-[1,2,4]triazolo[1,5-a]pyridin-2-yl-ethyl)-3,5-dihydro-2H-pyrrolo[3,4-c]pyridine-1,6-dione (50 mg, 0.145 mmol, see Example c6)) and pyridin-3-ylboronic acid (19.67 mg, 0.160 mmol) in DMF (1 ml)/water (0.200 ml). The reaction mixture was heated in a microwave at about 120° C. for about 20 min. The mixture was purified by preparative HPLC (system: Waters 2767 PHW003, eluent: MeCN/ammonium acetate buffer (gradient: 5:95 to 30:70 over 15 min), column: Boston Analytics, C-18, 10 μm, 21×250 mm) to afford the title compound (25 mg, 0.065 mmol, 44.5% yield).

Workup

customThe mixture was purified by preparative HPLC (system: Waters 2767 PHW003, eluent: MeCN/ammonium acetate buffer (gradient: 5:95 to 30:70 over 15 min), column: Boston Analytics, C-18, 10 μm, 21×250 mm)

Sources & evidence

ORD record: ord-f849ac7f61164c1aa8933de2b5a93616
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09163019B2

Reaction notes

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