Triethylamine → 8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-ylamine

HRID 1849020Notes

Reaction equation

HRID 1849020 reaction equation
[Br:1][C:2]1[CH:18]=[CH:17][C:5]2[C:6]3[N:7]=[C:8](C(O)=O)[S:9][C:10]=3[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1.C([N:21](CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>C(O)(C)(C)C>[Br:1][C:2]1[CH:18]=[CH:17][C:5]2[C:6]3[N:7]=[C:8]([NH2:21])[S:9][C:10]=3[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 579001668-Bromo-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxylic acid

Product 1

HCID 579002668-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-ylamineYield 70%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

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 (12.5 g, 38.3 mmol) in tert-butanol (250 mL) were added triethylamine (5.5 mL, 40 mmol) and diphenylphosphoryl-azide (8.6 mL, 40 mmol). The reaction mixture was stirred at 95° C. for 16 hours, then allowed to cool down to RT, and concentrated in vacuo. The resultant residue was dissolved in EtOAc, washed successively with water, aqueous saturated sodium bicarbonate solution followed by brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was dissolved in DCM (150 mL) and treated with TFA (50 mL). The reaction mixture was stirred at RT for 3 hours then concentrated in vacuo. The resulting residue was triturated with 20% EtOAc/cyclohexane and filtered to afford 8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-ylamine as an off-white solid (7.94 g, 70%). LCMS: RT=3.13 min, [M+H]+=297/299

Workup

  1. temperatureto cool down to RT
  2. concentrationconcentrated in vacuo
  3. dissolutionThe resultant residue was dissolved in EtOAc
  4. washwashed successively with water, aqueous saturated sodium bicarbonate solution
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resultant residue was dissolved in DCM (150 mL)
  8. additiontreated with TFA (50 mL)
  9. stirringThe reaction mixture was stirred at RT for 3 hours
  10. concentrationthen concentrated in vacuo
  11. customThe resulting residue was triturated with 20% EtOAc/cyclohexane
  12. filtrationfiltered

Sources & evidence

ORD record
ord-ce3528b680a24d2bbc6f9570c62851e1
Source dataset
uspto-grants-2015_02
Patent number
US08952043B2

Reaction notes

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