Cesium carbonate → 2-{4-[2-(2-Isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-piperidin-1-yl}-2-methyl-propionic acid ethyl ester

HRID 886374Notes

Reaction equation

Cl.[CH:2]([N:5]1[C:9]([C:10]2[N:19]=[C:18]3[N:12]([CH2:13][CH2:14][O:15][C:16]4[CH:23]=[C:22]([CH:24]5[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]5)[CH:21]=[CH:20][C:17]=43)[CH:11]=2)=[N:8][C:7]([CH3:30])=[N:6]1)([CH3:4])[CH3:3].[CH2:31]([O:33][C:34](=[O:39])[C:35](Br)([CH3:37])[CH3:36])[CH3:32].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH2:31]([O:33][C:34](=[O:39])[C:35]([N:27]1[CH2:28][CH2:29][CH:24]([C:22]2[CH:21]=[CH:20][C:17]3[C:18]4[N:12]([CH2:13][CH2:14][O:15][C:16]=3[CH:23]=2)[CH:11]=[C:10]([C:9]2[N:5]([CH:2]([CH3:4])[CH3:3])[N:6]=[C:7]([CH3:30])[N:8]=2)[N:19]=4)[CH2:25][CH2:26]1)([CH3:37])[CH3:36])[CH3:32]

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of 2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene hydrochloride (100 mg, 0.255 mmol), 2-bromo-2-methyl-propionic acid ethyl ester (45 uL, 0.31 mmol), cesium carbonate (187 mg, 0.57 mmol) and DMF (0.5 mL) was heated at 70° C. for 3 h the then stirred at RT for 18 h then heated again at 70° C. for 4 h before concentrating in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 5% methanol in DCM) to give 2-{4-[2-(2-Isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-piperidin-1-yl}-2-methyl-propionic acid ethyl ester (47 mg, 36%). LCMS RT=2.24, [M+H]+=507.

Workup

temperaturethen heated again at 70° C. for 4 h
concentrationbefore concentrating in vacuo

Sources & evidence

ORD record: ord-90807686989e4e8cac6c9ef35470cdfd
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08242104B2

Reaction notes

Loading…