Piperazin-2-one → 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-2-one

HRID 708100Notes

Reaction equation

HRID 708100 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[CH:10]=[C:9]([C:15]4[N:16]([C:20]5[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=5[F:27])[N:17]=[CH:18][N:19]=4)[S:8][C:7]=3[C:6]=2[N:28]=1.[NH:29]1[CH2:34][CH2:33][NH:32][CH2:31][C:30]1=[O:35].CC([O-])(C)C.[Na+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[N:16]1[C:15]([C:9]2[S:8][C:7]3[C:6]4[N:28]=[C:2]([N:32]5[CH2:33][CH2:34][NH:29][C:30](=[O:35])[CH2:31]5)[CH:3]=[CH:4][C:5]=4[O:14][CH2:13][CH2:12][C:11]=3[CH:10]=2)=[N:19][CH:18]=[N:17]1

Participants

7

Reactant 4

HCID 231360Piperazin-2-oneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 579003099-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene

Product 1

HCID 582037094-{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-2-oneYield 13%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of 9-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene (100 mg, 0.24 mmol), piperazin-2-one (48 mg, 0.48 mmol), tBuONa (47 mg, 0.48 mmol), Pd2(dba)3 (22 mg, 0.2 mmol) and Xphos (23 mg, 0.048 mmol) in dioxane (2 mL) was bubbled N2 for 10 min and then stirred at 115° C. for 5 min under the irradition of microwave. The mixture was filtered by celite. The filtrate was concentrated to dryness and purified by pre-TLC (EtOAc) and pre-HPLC to afford 15 mg of 352. (yield: 13%)1H NMR (CDCl3, 400 MHz): δ8.02 (s, 1H, ArH), 7.49-6.96 (m, 5H), 6.41 (d, J=8.8 Hz, 1H), 5.95 (s, 1H), 4.19 (t, J=4.8 Hz, 2H), 3.99 (s, 2H), 3.76 (t, J=5.2 Hz, 2H), 3.47 (t, J=5.2 Hz, 2H), 3.06 (t, J=4.8 Hz, 2H). LC-MS (ESI): m/z=481 [M+H]+

Workup

  1. customwas bubbled N2 for 10 min
  2. filtrationThe mixture was filtered by celite
  3. concentrationThe filtrate was concentrated to dryness
  4. custompurified by pre-TLC (EtOAc)

Sources & evidence

ORD record
ord-0fa75b38238f43e988c920ce5856bdba
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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