rel-(2R,6S)-2,6-dimethylpiperazine → HCID 57900099, compound

HRID 2385840Notes

Reaction equation

HRID 2385840 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.[CH3:29][C@H:30]1[CH2:35][NH:34][CH2:33][C@@H:32]([CH3:36])[NH:31]1.CC([O-])(C)C.[Na+].C(N1CCN2CCN(CCCC)P1N(CCCC)CC2)CCC>CC([O-])=O.CC([O-])=O.[Pd+2]>[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:34]5[CH2:33][C@H:32]([CH3:36])[NH:31][C@H:30]([CH3:29])[CH2:35]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

6

Reactant 4

HCID 6950261rel-(2R,6S)-2,6-dimethylpiperazineHCID 23676156Sodium t-butoxideHCID 575886892,8,9-Tributyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecaneHCID 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 57900099HCID 57900099, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
120 °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 (300 mg, 0.72 mmol), (2S,6R)-2,6-dimethylpiperazine (164 mg, 1.44 mmol), tBuONa (47 mg, 0.48 mmol), Pd(OAc)2 (49 mg, 0.3 mmol) and 2,8,9-tributyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (99 mg, 0.29 mmol), in dioxane (2 mL) was bubbled N2 for 10 min and then stirred at 120° C. for 1 h under the irradition of microwave. The mixture was filtered by celite. The filtrate was concentrated to dryness and purified by pre-TLC(EtOAc) to afford 220 mg of 2-[2-(2,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-9-((3R,5S)-3,5-dimethyl-piperazin-1-yl)-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene. (Yield: 62%) 1H NMR (DMSO, 400 MHz): δ8.28 (s, 1H), 8.22 (s, 1H), 7.94-7.88 (m, 1H), 7.72-7.67 (m, 1H), 7.40 (d, J=2.4 Hz, 1H), 7.24 (t, J=2.4 Hz, 1H), 6.79 (d, J=8.8 Hz, 1H), 4.20 (t, J=4.4 Hz, 2H), 3.99 (q, J=2.4, 12.8 Hz, 2H), 3.12 (t, J=4.8 Hz, 2H), 2.87-2.82 (m, 2H), 1.10 (d, J=6.0 Hz, 6H). LC-MS (ESI): m/z=495 [M+H]+

Workup

  1. customin dioxane (2 mL) was 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-cb1c9a973c32401ca016bc6582ff8b8d
Source dataset
uspto-grants-2012_09
Patent number
US08263633B2

Reaction notes

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