Reaktion #317714

Reaktionsgleichung

hydrazine monohydrate

K2CO3

4-(4-methyl-1,4-diazepan-1-yl)-3-nitro-N-phenylbenzenesulfonamide

HCl ether

1-Methylhomopiperazine

4-chloro-3-nitro-N-phenylbenzenesulfonamide

→

3-Amino-4-(4-methyl-1,4-diazepan-1-yl)-N-phenylbenzenesulfonamide

Lösungsmittel

diethyl ether EtOAc

EtOH THF

CH2Cl2

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was heated to reflux
2. 2
   Einengenthe solution was concentrated under vacuum
3. 3
   Extraktionthe product was extracted
4. 4
   Sonstigeto give
5. 5
   Trocknenafter drying with Na2SO4 and concentration, 450 mg (72%) of 4-(4-methyl-1,4-diazepan-1-yl)-3-nitro-N-phenylbenzenesulfonamide as an orange oil
6. 6
   workup.ADDITIONwere added
7. 7
   Filtrationthe mixture was filtered
8. 8
   Einengenthe yellow solution concentrated
9. 9
   Sonstigeto give yellow oil
10. 10
    FiltrationThe resulting precipitate was filtered
11. 11
    Waschenwashed with ether
12. 12
    Sonstigeto give
13. 13
    Sonstigeafter drying under vacuum at 40° C.

Vorschrift

4-Chloro-3-nitrobenzenesulfonyl chloride (460 mg, 1.8 mmol) was added to a colorless solution of aniline (250 mg, 2.7 mmol) in CH2Cl2 (10 mL) followed by pyridine (0.80 mL, 10.0 mmol). The resulting orange solution was stirred at room temperature for 30 minutes, after which time the mixture was concentrated under vacuum. Acidification with 2M aq. HCl followed by extraction using EtOAc and drying with Na2SO4 followed by filtration through a plug of silica, gave 500 mg (62%) of 4-chloro-3-nitro-N-phenylbenzenesulfonamide. 1H NMR (CDCl3) δ 8.30 (d, 1H), 7.80 (dd, 2H), 7.55 (d, 1H), 7.20 (m, 5H). MS(negESI) m/z=311(M−H+). 1-Methylhomopiperazine (258 mg, 2.3 mmol) was added to a solution of 4-chloro-3-nitro-N-phenylbenzenesulfonamide obtained as above (500 mg, 1.6 mmol) in CH2Cl2 (20 mL) followed by addition of K2CO3 (310 mg, 2.3 mmol). The reaction mixture was heated to reflux. After 2.5 h, the solution was concentrated under vacuum. After adjusting to pH=6, the product was extracted using EtOAc to give, after drying with Na2SO4 and concentration, 450 mg (72%) of 4-(4-methyl-1,4-diazepan-1-yl)-3-nitro-N-phenylbenzenesulfonamide as an orange oil. 1H NMR (CDCl3) δ 8.15 (d, 1H), 7.60 (dd, 1H), 7.15 (m), 6.95 (d, 1H), 3.45 (m, 2H), 3.30 (m, 2H), 2.75 (m, 2H), 2.60 (m, 2H), 2.35 (s, 3H), 1.95 (m, 2H). MS (posESI) m/z=391(M+H+). To a solution of 4-(4-methyl-1,4-diazepan-1-yl)-3-nitro-N-phenylbenzenesulfonamide (225 mg, 0.58 mmol) in EtOH/THF (4/1, 25 mL) activated Raney-Ni (slurry in EtOH) and hydrazine monohydrate (142 μL, 2.9 mmol) were added. After stirring for 30 minutes at room temperature, the mixture was filtered and the yellow solution concentrated to give yellow oil. The oil was dissolved in a mixture diethyl ether/EtOAc followed by addition of excess of HCl/ether. The resulting precipitate was filtered and washed with ether to give, after drying under vacuum at 40° C., 88 mg (38%) of 3-amino-4-(4-methyl-1,4-diazepan-1-yl)-N-phenylbenzenesulfonamide as a beige solid. Mp 84-85° C. MS (posESI) m/z=361 (M+H+). 1H NMR (MeOH-d3) δ 7.85 (d, 2H), 7.60 (d, 1H), 7.15 (m, 5H), 3.50 (m, 7H), 3.15 (m, 2H), 3.00 (s, 3H), 2.30 (m, 1H), 2.20 (m, 1H). Anal. (C18H24N4SO2.2HCl) C, H, N, S.

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