Reaction SMILES: FC1C=CC(C2C(C(N(C)C(=O)OC(C)(C)C)=O)=[C:15]3[N:10]([N:11]=[CH:12][C:13]([C:28]4[CH:33]=[C:32]([C:34](=[O:45])[NH:35][C:36]5([C:39]6[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=6)[CH2:38][CH2:37]5)[CH:31]=[CH:30][C:29]=4[CH3:46])=[CH:14]3)[N:9]=2)=CC=1.FC1C=CC(C2C(C(N(C)C(=O)OC(C)(C)C)=O)=C3N(N=CC=C3C3C=C(C(=O)NC4(C5C=CC=CC=5)CC4)C=CC=3C)N=2)=CC=1.CC1C=CC(C(NC2(C3C=CC=CC=3)CC2)=O)=CC=1C1C=CN=NC=1.[C:118]1([CH3:131])[CH:123]=[C:122]([CH3:124])[CH:121]=[C:120]([CH3:125])[C:119]=1[S:126]([O:129]N)(=[O:128])=[O:127]>ClCCl>[CH3:125][C:120]1[CH:121]=[C:122]([CH3:124])[CH:123]=[C:118]([CH3:131])[C:119]=1[S:126]([O-:129])(=[O:128])=[O:127].[NH2:9][N+:10]1[CH:15]=[CH:14][C:13]([C:28]2[CH:33]=[C:32]([C:34](=[O:45])[NH:35][C:36]3([C:39]4[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=4)[CH2:37][CH2:38]3)[CH:31]=[CH:30][C:29]=2[CH3:46])=[CH:12][N:11]=1
Reactant: Cc1ccc(C(=O)NC2(c3ccccc3)CC2)cc1-c1cnn2nc(-c3ccc(F)cc3)c(C(=O)N(C)C(=O)OC(C)(C)C)c2c1
Reactant: Cc1cc(C)c(S(=O)(=O)ON)c(C)c1
Agent: Cc1ccc(C(=O)NC2(c3ccccc3)CC2)cc1-c1ccnn2nc(-c3ccc(F)cc3)c(C(=O)N(C)C(=O)OC(C)(C)C)c12
Agent: Cc1ccc(C(=O)NC2(c3ccccc3)CC2)cc1-c1ccnnc1
Solvent: ClCCl
Product: Cc1cc(C)c(S(=O)(=O)[O-])c(C)c1
Product: Cc1ccc(C(=O)NC2(c3ccccc3)CC2)cc1-c1cc[n+](N)nc1
Temperature: 0 °C
Reaction time: 0.33 h

Procedure:
tert-butyl 2-(4-fluorophenyl)-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-b]pyridazine-3-carbonyl(methyl)carbamate and tert-butyl 2-(4-fluorophenyl)-4-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-b]pyridazine-3-carbonyl(methyl)carbamate. Part A: To a cooled solution (0° C., ice bath) containing 4-methyl-N-(1-phenylcyclopropyl)-3-(pyridazin-4-yl)benzamide (0.21 g, 0.55 mmol) and dichloromethane (4 mL) was added O-(mesitylsulfonyl)hydroxylamine (0.23 g, 0.58 mmol) in dichloromethane (3 mL) quickly, dropwise. The solution was maintained at 0° C. for 5 min, removed from the cooling bath and maintained at ambient temperature for 45 min. The solution was concentrated to a foam and suspended in n-pentane (5 mL) with stirring for 20 min. The solid was collected by filtration and air dried to afford 1-amino-4-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyridazin-1-ium 2,4,6-trimethylbenzenesulfonate as a yellow powder (345 MH+). Part B: The product thus obtained in part A was suspended in THF (3.7 mL). tert-butyl 3-(4-fluorophenyl)propioloyl(methyl)carbamate (0.19 g, 0.69 mmol) was added and the suspension cooled to −78° C. (dry Ice/acetone bath). DBU (0.17 g, 1.14 mmol) in THF (2 mL) was added dropwise over 5 min. The mixture was left in the cooling bath and allowed to proceed for 20 h at ambient temperature. The mixture was concentrated. Purification on silica gel (30-100% ethyl acetate/hexanes, 60 min gradient) afforded tert-butyl 2-(4-fluorophenyl)-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-b]pyridazine-3-carbonyl(methyl)carbamate and tert-butyl 2-(4-fluorophenyl)-4-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-b]pyridazine-3-carbonyl(methyl)carbamate as separate regioisomers. Tert-butyl 2-(4-fluorophenyl)-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-b]pyridazine-3-carbonyl(methyl)carbamate: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.35 (d, J=2.26 Hz, 1 H), 8.12 (d, J=2.51 Hz, 1 H), 7.70-7.83 (m, 4 H), 7.42 (d, J=8.03 Hz, 1 H), 7.28-7.37 (m, 5 H), 7.13-7.24 (m, 3 H), 6.91 (s, 1 H), 3.29 (s, 3 H), 2.40 (s, 3 H), 1.40 (d, J=6.27 Hz, 4 H), 1.10 (s, 9 H) LCMS retention time: 2.731 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 10 micron, C18, 3.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10% methanol/90% H2O/10 mM TFA and solvent B was 10% H2O/90% methanol/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 620 (MH+). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.68 (d, J=2.51 Hz, 1 H), 8.43 (d, J=2.26 Hz, 1 H), 7.85 (dd, J=7.91, 1.88 Hz, 1 H), 7.72-7.81 (m, 3 H), 7.45 (d, J=8.03 Hz, 1 H), 7.28-7.36 (m, 5 H), 7.16-7.27 (m, 3 H), 5.90 (d, J=4.52 Hz, 1 H), 2.90 (d, J=5.02 Hz, 3 H), 2.43 (s, 3 H), 1.42 (s, 2 H), 1.35-1.41 (m, 2 H). Tert-butyl 2-(4-fluorophenyl)-4-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-b]pyridazine-3-carbonyl(methyl)carbamate: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.41 (t, J=5.14 Hz, 1 H), 7.79-7.92 (m, 3 H), 7.46-7.58 (m, 2 H), 7.41 (d, J=8.03 Hz, 1 H), 7.28-7.39 (m, 4 H), 7.10-7.23 (m, 3 H), 6.88-6.97 (m, 1 H), 2.59 (s, 1 H), 2.49 (s, 2 H), 2.39 (s, 1 H), 2.12 (s, 2 H), 1.30-1.43 (m, 4 H), 0.96-1.06 (m, 9 H). LCMS retention time: 2.616 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 10 micron, C18, 3.0×50 mm column using a SPD-10AV UV-V is detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10% methanol/90% H2O/10 mM TFA and solvent B was 10% H2O/90% methanol/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 620 (MH+).