p-Toluenesulfonic acid → 1-{4-[3-Methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6,12-triazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaen-13-yl}ethan-1-one

HRID 1530715Notes

Reaction equation

C([O:3][C:4]([C:6]1[CH:19]=[C:18]2[C:9]([O:10][CH2:11][CH2:12][N:13]3[C:17]2=[N:16][C:15]([C:20]2[N:24]([CH:25]([CH3:27])[CH3:26])[N:23]=[C:22]([CH3:28])[N:21]=2)=[CH:14]3)=[CH:8][N:7]=1)=[CH2:5])C.CC1C=CC(S(O)(=O)=O)=CC=1>CC(C)=O>[CH3:28][C:22]1[N:21]=[C:20]([C:15]2[N:16]=[C:17]3[N:13]([CH:14]=2)[CH2:12][CH2:11][O:10][C:9]2[C:18]3=[CH:19][C:6]([C:4](=[O:3])[CH3:5])=[N:7][CH:8]=2)[N:24]([CH:25]([CH3:27])[CH3:26])[N:23]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 13-(1-ethoxyethenyl)-4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6,12-triazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene (900 mg, 2.36 mmol) and 4-methylbenzenesulfonic acid (204 mg, 1.18 mmol) in acetone (20 mL) was stirred at 60° C. for 75 min. After removal of the solvent, the residue was purified by reverse phase Combi-flash eluting with a 23-27% gradient of CH3CN in 0.3% NH4HCO3 to give the desired product (650 mg, 74% yield) as a pale yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 8.85 (s, 1H), 8.49 (s, 1H), 8.07 (s, 1H), 5.69 (m, 1H), 4.68-4.59 (m, 4H), 2.63 (s, 3H), 2.29 (s, 3H), 1.49 (s, 6H). LCMS m/z [M+H]+ 353.3

Workup

customAfter removal of the solvent
customthe residue was purified by reverse phase Combi-flash
washeluting with a 23-27% gradient of CH3CN in 0.3% NH4HCO3

Sources & evidence

ORD record: ord-4bdcfc16b7d84dbbbd117c26caabbe13
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090628B2

Reaction notes

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