Methanesulfonyl chloride → 2-[2-(2,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-9-(4-methanesulfonyl-piperazin-1-yl)-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene

HRID 707884Notes

Reaction equation

HRID 707884 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.[CH3:43][S:44](Cl)(=[O:46])=[O:45].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]([S:44]([CH3:43])(=[O:46])=[O:45])[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 31297Methanesulfonyl 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 582038792-[2-(2,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-9-(4-methanesulfonyl-piperazin-1-yl)-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azuleneYield 26%

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, DIPEA (155 mg, 1.2 mmol) was added. Methanesulfonyl chloride (41 mg, 0.36 mmol) was added dropwise into the solution, and 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 over Na2SO4, concentrated in vacuo, and purified by prep. TLC (DCM/EtOAc=10:1) to give 130 (42.0 mg, yield: 26%). 1HNMR (Acetone, 400 MHz): δ8.00 (s, 1H), 7.73-7.71 (m, 1H), 7.36-7.10 (m, 2H), 7.12 (s, 2H), 6.69 (d, J=9.2 Hz, 1H), 4.14 (s, 1H), 3.49 (s, 4H), 3.22 (s, 4H), 3.00 (s, 2H), 2.79 (s, 3H). ESI-MS: m/z=545 [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 over Na2SO4
  5. concentrationconcentrated in vacuo
  6. custompurified by prep

Sources & evidence

ORD record
ord-a01a424dfda349d59f0832aa397719f0
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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