Cesium carbonate → 8-[(4-Methoxyphenyl)methyl]-12-(3-methyl-6-oxopyridazin-1-yl)-3,5,6,8,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),2,4,10,12-pentaen-7-one

HRID 926113

Reaction equation

Br[C:2]1[CH:11]=[N:10][C:9]2[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[C:7](=[O:21])[N:6]3[N:22]=[CH:23][N:24]=[C:5]3[C:4]=2[CH:3]=1.[CH3:25][C:26]1[CH:27]=[CH:28][C:29](=[O:32])[NH:30][N:31]=1.N[C@@H]1CCCC[C@H]1N.C([O-])([O-])=O.[Cs+].[Cs+]>[Cu]I.O1CCOCC1>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([CH2:12][N:8]2[C:9]3[N:10]=[CH:11][C:2]([N:30]4[C:29](=[O:32])[CH:28]=[CH:27][C:26]([CH3:25])=[N:31]4)=[CH:3][C:4]=3[C:5]3=[N:24][CH:23]=[N:22][N:6]3[C:7]2=[O:21])=[CH:14][CH:15]=1

Participants

Conditions

Temperature: 120 °C

Procedure

9-Bromo-6-(4-methoxybenzyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one (Example 1, 75 mg, 0.19 mmol), 6-methylpyridazin-3(2H)-one (43 mg, 0.39 mmol), copper(I) iodide (44 mg, 0.23 mmol), dioxane (3 mL), trans-1,2-diaminocyclohexane (0.030 mL, 0.25 mmol) and Cs2CO3 (152 mg, 0.47 mmol) were combined and heated at 120° C. for 12 h in the microwave. The mixture was filtered, and purified (HPLC, 10-80% ACN-water) to afford the title compound (9 mg, 11%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 2.44 (s, 3H), 3.76 (s, 3H), 5.77 (s, 2H), 6.81-6.83 (m, 2H), 7.03 (d, J=7.7 Hz, 1H), 7.60-7.61 (m, 2H), 8.36 (s, 1H), 8.99 (d, J=2.1 Hz, 1H), 9.25 (d, J=2.1 Hz, 1H). [M+H]=416.1.

Workup

filtrationThe mixture was filtered
custompurified (HPLC, 10-80% ACN-water)

Sources & evidence

ORD record: ord-81f0306bdd7d4ff28ac76a0d5a8413d3
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09284335B2

Linked notes

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