Acetyl chloride → 1-(4-{2-[2-(2,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulen-9-yl}-piperazin-1-yl)-ethanone

HRID 1849273Notes

Reaction equation

HRID 1849273 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([C:14]2[S:23][C:22]3[C:21]4[N:24]=[C:25]([N:28]5[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]5)[CH:26]=[CH:27][C:20]=4[O:19][CH2:18][CH2:17][C:16]=3[CH:15]=2)=[N:12][CH:11]=[N:10]1.CCN(C(C)C)C(C)C.[C:43](Cl)(=[O:45])[CH3:44].C(Cl)Cl.CCOC(C)=O>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([C:14]2[S:23][C:22]3[C:21]4[N:24]=[C:25]([N:28]5[CH2:29][CH2:30][N:31]([C:43](=[O:45])[CH3:44])[CH2:32][CH2:33]5)[CH:26]=[CH:27][C:20]=4[O:19][CH2:18][CH2:17][C:16]=3[CH:15]=2)=[N:12][CH:11]=[N:10]1

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 21226138Dichloromethane ethylacetateHCID 579005292-[2-(2,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-9-piperazin-1-yl-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene

Product 1

HCID 582039581-(4-{2-[2-(2,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulen-9-yl}-piperazin-1-yl)-ethanoneYield 28%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-[2-(2,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-9-piperazin-1-yl-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene (150 mg, 0.3 mmol) was dissolved in THF (20 mL), and DIPEA (155 mg, 1.2 mmol) was added. Acetyl chloride (28 mg, 0.36 mmol) was added dropwise into the solution. And then the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and then dissolved in DCM. The mixture was washed by water, dried by Na2SO4, concentrated in vacuo, and purified by prep. TLC (DCM/EtOAc=10:1) to give 348 (42.6 mg, yield: 28%). 1HNMR (DMSO, 400 MHz): δ8.29 (s, 1H), 7.97-7.88 (m, 1H), 7.78 (t, J=2.4 Hz, 1H), 7.47 (t, J=8.4 Hz, 1H), 7.27-7.24 (m, 2H), 6.80 (d, J=8.8 Hz, 1H), 4.20 (s, 1H), 3.63 (s, 4H), 3.33 (s, 4H), 3.11 (s, 2H), 2.07 (s, 3H). ESI-MS: m/z=509 [M+H+]

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutiondissolved in DCM
  3. washThe mixture was washed by water
  4. dry with materialdried by Na2SO4
  5. concentrationconcentrated in vacuo
  6. custompurified by prep

Sources & evidence

ORD record
ord-5bc360022c404b21a35e84255598046a
Source dataset
uspto-grants-2015_02
Patent number
US08952043B2

Reaction notes

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