Methanol → 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1-thia-benzo[e]azulene-9-carboxylic acid methyl ester

HRID 84663

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[CH:10]=[C:9]([C:15]4[N:19]([CH:20]([CH3:22])[CH3:21])[N:18]=[CH:17][N:16]=4)[S:8][C:7]=3[C:6]=2[CH:23]=1.C[OH:25].C1[CH2:30][O:29][CH2:28]C1.N12CCCN=C1CCCCC2>ClCCl.[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo]>[CH3:28][O:29][C:30]([C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[CH:10]=[C:9]([C:15]4[N:19]([CH:20]([CH3:22])[CH3:21])[N:18]=[CH:17][N:16]=4)[S:8][C:7]=3[C:6]=2[CH:23]=1)=[O:25]

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of 5-(9-bromo-4,5-dihydro-6-oxa-1-thia-benzo[e]azulen-2-yl)-1-isopropyl-1H-[1,2,4]triazole (290 mg), molybdenum hexacarbonyl (196 mg), Herman's catalyst (70 mg), tributyl phosphonic tetrafluoroborate (43 mg), methanol (3 mL), THF (3 mL) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.33 ml) was heated in the microwave at 130° C. for 30 minutes. The reaction mixture was cooled, and then diluted with dichloromethane, washed with water, dried (MgSO4) and the solvent removed in vacuo to yield 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1-thia-benzo[e]azulene-9-carboxylic acid methyl ester. This was hydrolyzed using sodium hydroxide in water/methanol/THF to yield the corresponding acid. Treatment with HATU, diisopropylethylamine and ammonium chloride in dry DMF yielded 419. NMR: (DMSO): 1.51 (6H, d), 3.25 (2H, t), 4.38 (2H, t), 5.09 (1H, septet), 7.02 (1H, d), 7.33 (1H, br, s), 7.51 (1H, s), 7.75 (1H, dd), 8.00 (1H, s), 8.04 (1H, s, br.), 8.18 (1H, s). MS. ESI+ 3396 (MH++MeCN)

Workup

temperatureThe reaction mixture was cooled
washwashed with water
dry with materialdried (MgSO4)
customthe solvent removed in vacuo

Sources & evidence

ORD record: ord-82f418ed49874e60b52bd7bdd9971012
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846762B2

Linked notes

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