Methylamine → 8-Bromo-2-[2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

HRID 707845Notes

Reaction equation

[Br:1][C:2]1[CH:18]=[CH:17][C:5]2[C:6]3[N:7]=[C:8]([C:14]([NH2:16])=O)[S:9][C:10]=3[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1.[CH3:19]N.[F:21][C:22]([F:27])([F:26])[CH2:23][NH:24][NH2:25]>C1(C)C=CC=CC=1.C(O)(=O)C>[Br:1][C:2]1[CH:18]=[CH:17][C:5]2[C:6]3[N:7]=[C:8]([C:14]4[N:24]([CH2:23][C:22]([F:27])([F:26])[F:21])[N:25]=[CH:19][N:16]=4)[S:9][C:10]=3[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 95 °C

Procedure

To a solution of 8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide 25 (10.76 g, 0.03308 mol) in toluene (200 mL) was added methanamine, 1,1-Dimethoxy-N,N-dimethyl-(19.683 g, 0.1640 moles). The reaction was heated to 95° C. for 3 hours. The toluene was removed in vacuo to give a beige powder. The crude (12.58 g, 0.03308 mol) was redissolved in acetic acid (120 mL) and trifluoroethyl hydrazine (6.269 mL, 0.04962 mol) was added. The reaction was heated to 95° C. for 4 h. The AcOH was removed in vacuo. The product was loaded as a solid onto silica and purified by flash chromatography (5-70% EtOAc in hexanes). The appropriate fractions were combined and concentrated to give 8-Bromo-2-[2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene (6.176 g) as an off-white solid. MS(ESI+) 431.0/433.0.

Workup

customThe toluene was removed in vacuo
customto give a beige powder
temperatureThe reaction was heated to 95° C. for 4 h
customThe AcOH was removed in vacuo
custompurified by flash chromatography (5-70% EtOAc in hexanes)
concentrationconcentrated

Sources & evidence

ORD record: ord-bd949a22c6e945a29dcca7b712297950
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09175009B2

Reaction notes

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