rel-(2R,6S)-2,6-dimethylpiperazine → HCID 57900094, compound

HRID 1190518Notes

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](C4N(C5C=CC(F)=CC=5F)N=CN=4)[S:8][C:7]=3[C:6]=2[N:28]=1.C[C@H]1CNC[C@@H](C)N1.CC([O-])(C)C.[Na+].C(N1CCN2CCN(CCCC)P1N(CCCC)CC2)CCC>CC([O-])=O.CC([O-])=O.[Pd+2]>[S:8]1[C:7]2[C:6]3[N:28]=[CH:2][CH:3]=[CH:4][C:5]=3[O:14][CH2:13][CH2:12][C:11]=2[CH:10]=[CH:9]1

Participants

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

customin dioxane (2 mL) was bubbled N2 for 10 min
filtrationThe mixture was filtered by celite
concentrationThe filtrate was concentrated to dryness
custompurified by pre-TLC (EtOAc)

Sources & evidence

ORD record: ord-250d167bb56245b5949c2f9713dc8394
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08673952B2

Reaction notes

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