Diisopropylethylamine → (S)-9-Fluoro-5-[3-(2-methoxy-ethyl)-piperazine-1-yl]-11H-12-thia-6,11-diaza-dibenzo[a,f]azulene

HRID 131517Notes

Reaction equation

Cl.[F:2][C:3]1[CH:4]=[CH:5][C:6]2[N:15]=[C:14]([NH2:16])[C:13]3[C:12]4[CH:17]=[CH:18][CH:19]=[CH:20][C:11]=4[S:10][C:9]=3[NH:8][C:7]=2[CH:21]=1.[CH3:22][O:23][CH2:24][CH2:25][C@H:26]1[CH2:31]N[CH2:29][CH2:28][NH:27]1.C(N(C(C)C)CC)(C)C>CS(C)=O.C1(C)C=CC=CC=1.C(Cl)Cl>[F:2][C:3]1[CH:4]=[CH:5][C:6]2[N:15]=[C:14]([N:16]3[CH2:29][CH2:28][NH:27][C@@H:26]([CH2:25][CH2:24][O:23][CH3:22])[CH2:31]3)[C:13]3[C:12]4[CH:17]=[CH:18][CH:19]=[CH:20][C:11]=4[S:10][C:9]=3[NH:8][C:7]=2[CH:21]=1

Participants

Conditions

Temperature: 110 °C

Procedure

Combine 9-fluoro-11H-12-thia-6,11-diaza-dibenzo[a,f]azulen-5-ylamine hydrogen chloride (510.2 mg, 1.6 mmol, (S)-2-(2-methoxy-ethyl) piperazine (460.8 mg, 3.2 mmol) and diisopropylethyl amine (206 mg, 1.6 mmol) in DMSO (0.75 mL) and toluene (3.0 mL), stir and heat to 110° C. After 55 hours, cool the reaction to RT, dilute with CH2Cl2, wash with H2O and Brine. Dry the organic layer with by Na2SO4. The crude material pass through a 5 g SCX column, collect the 0.2 N NH3/MeOH eluent, concentrate to a residue, which purified by chromatography on silica gel, gradient (100% CH2Cl2 to 100% CH2Cl2: 2N NH3/MeOH=15:1), give 410 mg of title compound. Mass spectrum: ACPI (m/e): 411.2 (M+1).

Workup

temperaturecool
customthe reaction to RT
washwash with H2O and Brine
dry with materialDry the organic layer with by Na2SO4
customThe crude material pass through a 5 g SCX column, collect the 0.2 N NH3/MeOH eluent
concentrationconcentrate to a residue, which
custompurified by chromatography on silica gel, gradient (100% CH2Cl2 to 100% CH2Cl2: 2N NH3/MeOH=15:1)

Sources & evidence

ORD record: ord-dd6e4b61d46f4ba6a7a67d3a610f9cf2
Source dataset: uspto-grants-2008_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07384934B2

Reaction notes

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