Acetic Acid → 8-Bromo-2-(1H-imidazol-2-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

HRID 1190281Notes

Reaction equation

HRID 1190281 reaction equation
[Br:1][C:2]1[CH:17]=[CH:16][C:5]2[C:6]3[N:7]=[C:8]([C:14]#[N:15])[S:9][C:10]=3[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1.C[O-].[Na+].CO[CH:23](OC)[CH2:24][NH2:25].C(O)(=O)C.Cl>CO.O>[Br:1][C:2]1[CH:17]=[CH:16][C:5]2[C:6]3[N:7]=[C:8]([C:14]4[NH:25][CH:24]=[CH:23][N:15]=4)[S:9][C:10]=3[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 89728Aminoacetaldehyde dimethyl acetalHCID 10942334Sodium MethoxideHCID 58203878HCID 58203878, compound

Product 1

HCID 1360309128-Bromo-2-(1H-imidazol-2-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent3×HCID 962WaterSolvent

Procedure

To a solution of 8-bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carbonitrile (0.100 g, 0.326 mmol;) in 1.0 ml of Methanol was added 25% Sodium methoxide (0.020 mL, 0.087 mmol;) in Methanol. The reaction was stirred 1 h rt. Aminoacetaldehyde dimethyl acetal (0.0390 mL, 0.358 mmol;) was added to the reaction mixture followed by Acetic acid (0.0370 mL, 0.651 mmol;). The reaction was heated at 50° C. for 1 h and then cooled to rt. Methanol (0.650 mL, 16.0 mmol;) and 6.00 M of Hydrogen chloride in Water (0.163 mL) were added, the reaction was heated 100 for 12 h. The reaction mixture was concentrated then added EtOAc and water. The combined organic layers was concentrated to give 8-Bromo-2-(1H-imidazol-2-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene. MS: (ESI+)=349.1

Workup

  1. temperatureThe reaction was heated at 50° C. for 1 h
  2. temperaturecooled to rt
  3. temperaturethe reaction was heated 100 for 12 h
  4. concentrationThe reaction mixture was concentrated
  5. concentrationThe combined organic layers was concentrated

Sources & evidence

ORD record
ord-c5d13cff58834867b7e79322f2c65778
Source dataset
uspto-grants-2014_03
Patent number
US08673952B2

Reaction notes

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