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

HRID 2079029Notes

Reaction equation

HRID 2079029 reaction equation
C([Mg]Br)C.[CH:5]1([C:8]#[CH:9])[CH2:7][CH2:6]1.[N:10]([C:13]1[S:14][C:15]2[CH2:16][CH2:17][O:18][C:19]3[CH:26]=[C:25]([Br:27])[CH:24]=[CH:23][C:20]=3[C:21]=2[N:22]=1)=[N+:11]=[N-:12]>C1COCC1>[Br:27][C:25]1[CH:24]=[CH:23][C:20]2[C:21]3[N:22]=[C:13]([N:10]4[C:8]([CH:5]5[CH2:7][CH2:6]5)=[CH:9][N:12]=[N:11]4)[S:14][C:15]=3[CH2:16][CH2:17][O:18][C:19]=2[CH:26]=1

Participants

5

Reactant 3

HCID 138823CyclopropylacetyleneHCID 579001042-Azido-8-bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azuleneHCID 178418443HCID 178418443, compound

Product 1

HCID 579002148-Bromo-2-(5-cyclopropyl-[1,2,3]triazol-1-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azuleneYield 73.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To a 1M solution of ethylmagnesium bromide in THF (1.3 mL, 1.3 mmol) under a nitrogen atmosphere, was added dropwise cyclopropylethyne (70% in toluene, 0.154 mL, 1.3 mmol). The reaction mixture was heated at 50° C. for 15 mins then allowed to cool down to RT. A solution of 2-azido-8-bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene (425 mg, 1.3 mmol) in THF (1.5 mL) was then added dropwise. The reaction mixture was stirred at RT for 2 h, quenched with aqueous saturated ammonium chloride and diluted with ethyl acetate. The organic layer was washed with brine, dried (Na2SO4) and concentrated in vacuo. The resultant residue was triturated with 20% ethyl acetate/cyclohexane and filtered to afford the title compound as a pale yellow solid (373 mg, 64%). LCMS 110142391 (Method B): RT=4.40 min, [M+H]+=390. 1H NMR (DMSO-d6): 8.20 (1H, d, J=8.6 Hz), 7.71 (1H, d, J=0.7 Hz), 7.36 (1H, dd, J=8.6, 2.1 Hz), 7.30 (1H, d, J=2.1 Hz), 4.40 (2H, t, J=5.0 Hz), 3.41 (2H, t, J=5.0 Hz), 2.70-2.63 (1H, m), 1.21-1.15 (2H, m), 0.91-0.86 (2H, m).

Workup

  1. temperatureto cool down to RT
  2. customquenched with aqueous saturated ammonium chloride
  3. additiondiluted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was triturated with 20% ethyl acetate/cyclohexane
  8. filtrationfiltered

Sources & evidence

ORD record
ord-c2174e2ded24471d94275a2016684a0e
Source dataset
uspto-grants-2011_04
Patent number
US07928248B2

Reaction notes

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