3-AMINO-4-BROMO-1-METHYLPYRAZOLE

General procedure: Amino-pyr azole 1 (0.291 g, 0.003 mol) and an aqueous solution of NaBr (100 mL) (concentrations were as follows: 1 in entries 1 and 2, 2 Min entries 3 and 5-9, and 3 in entry 4) were placed in a cell. In experiment 2, NaHCO3 (0.504 g, 0.006 mol) was added to the solution. The electrolysis was carried out at the following currents: 426 mA for entries 1—4, 213 mA for entry 5, 710 mA for entries 6, 8, and 9, and 852 mA for entry 7. In experiment 9, 48percent aqueous solution of HBr was periodically added to the reaction mixture to maintain 7. After passing 2 F of electricity per 1 mole of the starting aminopyrazole 1(Q= 579 C) for entries 1—7or 8 F (Q= 2316 C) for entries 8and 9, the electrolysis was stopped, the reaction mixture was stirred for 1 h and analyzed by TLC (eluent light petroleum ether—ethyl acetate (1 : 1)). Then, the mixture obtained was diluted with concentrated HCl (to 3) and the products were extracted with CHCl3 (3×30 mL). The extracts were combined, dried with anhydrous MgSO4, and concentrated in vacuo. The products were isolated using column chromatography on SiO2 (eluent light petroleum ether-ethyl acetate). The following compounds were isolated: 1, 2-bis(1-methyl-1H-pyrazol-3-yl)-diazene (7) (entries 1-7; the product was identified by m.p. 201—202 °C (cf. Refs 2 and 4: m.p. 201 °C) and the reported 2, 41 NMR spectra) and 1, 2-bis(4-bromo-1-methyl-1H-pyrazol-3-yl)diazene (8) (entries 8 and 9, the product was identified by NMR spectroscopy and high resolution mass spectrometry). The aqueous layer obtained after extraction was concentrated in vacuo, diluted with NaOH with stirring (to 10), and treated as described above. This resulted in the isolation of 3-amino-4-bromo-1-methyl-1H-pyrazole (6) (entries 1-9; the product was identifi ed by m.p. 97 °C (cf. Ref. 10: m.p. 97-98 °C) and the reported 51 NMR spectra) and unreacted aminopyr-azole 1(entries 1-8; the starting compound was identified by TLC and NMR spectroscopy). 1, 2-Bis(4-bromo-1-methyl-1H-pyrazol-3-yl)diazene (8).Yellow crystals. M.p. 211—213 °C. Rf 0.13 (eluent light petroleum ether—ethyl acetate (1:5)). 1H NMR, :4.02 (s, 6 H, Me); 7.50 (s, 2 H, CH). 13C NMR, :40.4 (2 Me), 90.1 (2 CBr), 132.9 (2 CH), 157.5 (2 CN). Found: m/z 348.9217 [M + H]+. C8H979Br2N6. Calculated: [M + H]+= 348.9230General procedure: Amino-pyr azole 1 (0.291 g, 0.003 mol) and an aqueous solution of NaBr (100 mL) (concentrations were as follows: 1 in entries 1 and 2, 2 Min entries 3 and 5-9, and 3 in entry 4) were placed in a cell. In experiment 2, NaHCO3 (0.504 g, 0.006 mol) was added to the solution. The electrolysis was carried out at the following currents: 426 mA for entries 1—4, 213 mA for entry 5, 710 mA for entries 6, 8, and 9, and 852 mA for entry 7. In experiment 9, 48percent aqueous solution of HBr was periodically added to the reaction mixture to maintain 7. After passing 2 F of electricity per 1 mole of the starting aminopyrazole 1(Q= 579 C) for entries 1—7or 8 F (Q= 2316 C) for entries 8and 9, the electrolysis was stopped, the reaction mixture was stirred for 1 h and analyzed by TLC (eluent light petroleum ether—ethyl acetate (1 : 1)). Then, the mixture obtained was diluted with concentrated HCl (to 3) and the products were extracted with CHCl3 (3×30 mL). The extracts were combined, dried with anhydrous MgSO4, and concentrated in vacuo. The products were isolated using column chromatography on SiO2 (eluent light petroleum ether-ethyl acetate). The following compounds were isolated: 1, 2-bis(1-methyl-1H-pyrazol-3-yl)-diazene (7) (entries 1-7; the product was identified by m.p. 201—202 °C (cf. Refs 2 and 4: m.p. 201 °C) and the reported 2, 41 NMR spectra) and 1, 2-bis(4-bromo-1-methyl-1H-pyrazol-3-yl)diazene (8) (entries 8 and 9, the product was identified by NMR spectroscopy and high resolution mass spectrometry). The aqueous layer obtained after extraction was concentrated in vacuo, diluted with NaOH with stirring (to 10), and treated as described above. This resulted in the isolation of 3-amino-4-bromo-1-methyl-1H-pyrazole (6) (entries 1-9; the product was identifi ed by m.p. 97 °C (cf. Ref. 10: m.p. 97-98 °C) and the reported 51 NMR spectra) and unreacted aminopyr-azole 1(entries 1-8; the starting compound was identified by TLC and NMR spectroscopy).General procedure: A soln. of amine BB-34 (1 eq) and aldehyde or ketone BB-12 (1.05 to 1.1 eq) in MeOH (2 to 4 mL/mmol) was stirred for 1 h at RT. NaBI-U (1.6 to 2 eq) was added portionwise at 0C and the rxn mixture was stirred at a given temperature for a given time (see Table 52). It was quenched with H2O at 0C and extracted with EtOAc. The combined org. phases were washed with brine, dried over MgSCh and concentrated in vacuo. When necessary, the crude was purified by CC using EtOAc/MeOHGeneral procedure: A soln. of amine BB-34 (1 eq) and aldehyde or ketone BB-12 (1.05 to 1.1 eq) in MeOH (2 to 4 mL/mmol) was stirred for 1 h at RT. NaBI-U (1.6 to 2 eq) was added portionwise at 0C and the rxn mixture was stirred at a given temperature for a given time (see Table 52). It was quenched with H2O at 0C and extracted with EtOAc. The combined org. phases were washed with brine, dried over MgSCh and concentrated in vacuo. When necessary, the crude was purified by CC using EtOAc/MeOHTo a mixture of dimethyl 4-(bromomethyl)isophthalate (28.3 g), DIPEA (34.4 mL) and DMF (280 mL) was added General procedure: Amino-pyr azole 1 (0.291 g, 0.003 mol) and an aqueous solution of NaBr (100 mL) (concentrations were as follows: 1 in entries 1 and 2, 2 Min entries 3 and 5-9, and 3 in entry 4) were placed in a cell. In experiment 2, NaHCO3 (0.504 g, 0.006 mol) was added to the solution. The electrolysis was carried out at the following currents: 426 mA for entries 1-4, 213 mA for entry 5, 710 mA for entries 6, 8, and 9, and 852 mA for entry 7. In experiment 9, 48% aqueous solution of HBr was periodically added to the reaction mixture to maintain 7. After passing 2 F of electricity per 1 mole of the starting aminopyrazole 1(Q= 579 C) for entries 1-7or 8 F (Q= 2316 C) for entries 8and 9, the electrolysis was stopped, the reaction mixture was stirred for 1 h and analyzed by TLC (eluent light petroleum ether-ethyl acetate (1 : 1)). Then, the mixture obtained was diluted with concentrated HCl (to 3) and the products were extracted with CHCl3 (3×30 mL). The extracts were combined, dried with anhydrous MgSO4, and concentrated in vacuo. The products were isolated using column chromatography on SiO2 (eluent light petroleum ether-ethyl acetate). The following compounds were isolated: 1, 2-bis(1-methyl-1H-pyrazol-3-yl)-diazene (7) (entries 1-7; the product was identified by m.p. 201-202 C (cf. Refs 2 and 4: m.p. 201 C) and the reported 2, 41 NMR spectra) and 1, 2-bis(4-bromo-1-methyl-1H-pyrazol-3-yl)diazene (8) (entries 8 and 9, the product was identified by NMR spectroscopy and high resolution mass spectrometry). The aqueous layer obtained after extraction was concentrated in vacuo, diluted with NaOH with stirring (to 10), and treated as described above. This resulted in the isolation of General procedure: Amino-pyr azole 1 (0.291 g, 0.003 mol) and an aqueous solution of NaBr (100 mL) (concentrations were as follows: 1 in entries 1 and 2, 2 Min entries 3 and 5-9, and 3 in entry 4) were placed in a cell. In experiment 2, NaHCO3 (0.504 g, 0.006 mol) was added to the solution. The electrolysis was carried out at the following currents: 426 mA for entries 1-4, 213 mA for entry 5, 710 mA for entries 6, 8, and 9, and 852 mA for entry 7. In experiment 9, 48% aqueous solution of HBr was periodically added to the reaction mixture to maintain 7. After passing 2 F of electricity per 1 mole of the starting aminopyrazole 1(Q= 579 C) for entries 1-7or 8 F (Q= 2316 C) for entries 8and 9, the electrolysis was stopped, the reaction mixture was stirred for 1 h and analyzed by TLC (eluent light petroleum ether-ethyl acetate (1 : 1)). Then, the mixture obtained was diluted with concentrated HCl (to 3) and the products were extracted with CHCl3 (3×30 mL). The extracts were combined, dried with anhydrous MgSO4, and concentrated in vacuo. The products were isolated using column chromatography on SiO2 (eluent light petroleum ether-ethyl acetate). The following compounds were isolated: 1, 2-bis(1-methyl-1H-pyrazol-3-yl)-diazene (7) (entries 1-7; the product was identified by m.p. 201-202 C (cf. Refs 2 and 4: m.p. 201 C) and the reported 2, 41 NMR spectra) and 1, 2-bis(4-bromo-1-methyl-1H-pyrazol-3-yl)diazene (8) (entries 8 and 9, the product was identified by NMR spectroscopy and high resolution mass spectrometry). The aqueous layer obtained after extraction was concentrated in vacuo, diluted with NaOH with stirring (to 10), and treated as described above. This resulted in the isolation of General procedure: A 0.5M solution of NaOH in water (100mL) containing aminopyrazole 1 (3mmol, 0.29g) was placed into a glass cell with a cylindrical Ni anode (S=48cm2, activated before the synthesis according to the literature procedure23) and a Ti cathode (S=20cm2). Electrolysis was carried out at a current of 290mA. After passing 2F of electricity per mol of the substrate (Q=579C), the electrolysis was stopped. The reaction mixture was stirred for 0.5h and concentrated HCl was added until the solution was pH '3. The mixture was then extracted with CHCl3 (3×40mL). The extracts were combined, dried over Na2SO4 and concentrated in vacuo. Column chromatography on silica with light petroleum ether:ethyl acetate (10:1) gave the pure azopyrazole 1a (82%, 0.47g).A) Methyl 3-(4-bromo-1-methyl-1H-pyrazol-3-ylamino)propanoate A mixture of [0137] A mixture of (S)-N-(1-(4-chlorophenyl)propyl)-1-( 6-( 4, 4, 5, 5-tetramethyl-1 , 3, 2-dioxaborolan-2-yl)pyrrolo[1, 2-f][1, 2, 4]triazin-4-yl)azetidine-3-carboxamide (100 mg, 0.57 mmol),

Molecular Weight:176.01
XLogP3:0.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:174.97451
Monoisotopic Mass:174.97451
Topological Polar Surface Area:43.8
Heavy Atom Count:8
Complexity:87.4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes