Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C:7]([CH3:14])=[CH:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>[Ir].C(Cl)Cl>[C:1]1([CH:7]([CH3:14])[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCOC(=O)C=C(C)c1ccccc1
Agent: [Ir]
Solvent: ClCCl
Product: CCOC(=O)CC(C)c1ccccc1
Yield: 96.9 %

Procedure:
According to the general procedure, a solution of ethyl 3-phenylbut-2-enoate (57 mg, 0.29 mmol) and iridium catalyst (S)-32 (9.4 mg, 0.0060 mmol, 2 mol %) in CH2Cl2 (3 mL) was hydrogenated. Removal of the solvent in vacuo and standard purification gave 34 (54 mg, 94%) as a colorless oil. [α]20D −55.2 (c 1.00, CHCl3); CSP HPLC analysis (Chiralcel OB-H; eluent: 99.5:0.5 hexanes/i-PrOH, 0.5 mL/min) determined a 95:5 er (90% ee) [tR(major) 11.99 min, tR(minor) 14.09 min]; 1H NMR (300 MHz, CDCl3) 7.33-7.17 (m, 5H), 4.08 (q, 2H, J=6.9 Hz), 3.35-3.23 (sextet, 1H, J=7.2 Hz), 2.66-2.50 (m, 2H), 1.31 (d, 3H, J=6.9 Hz), 1.19 (t, 3H, J=6.9 Hz) ppm; 13C NMR (75 MHz, CDCl3) 172.4, 145.7, 128.4, 126.7, 126.3, 60.2, 43.0, 36.5, 21.8, 14.1 ppm.
Reaction SMILES: [CH:1]12[CH2:8][CH2:7][CH:4]([CH:5]=[CH:6]1)[CH:3]=[C:2]2[C:9]([OH:11])=[O:10]>CCOC(C)=O.[Pd]>[CH:1]12[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8]1)[CH:3]=[C:2]2[C:9]([OH:11])=[O:10]
Reactant: O=C(O)C1=CC2C=CC1CC2
Agent: [Pd]
Solvent: CCOC(C)=O
Product: O=C(O)C1=CC2CCC1CC2
Reaction time: 1.5 h
Yield: 98.8 %

Procedure:
Compound 11A (600 mg, 3.99 mmol) was dissolved in EtOAc (5 mL), 5% Pd/C (12 mg) was added and the mixture was stirred under a hydrogen balloon for 1.5 h. The reaction mixture was filtered through a pad of celite and concentrated under reduced pressure to give 600 mg of compound 11B as a yellow oil. No further purification was necessary. HPLC conditions: 95% at 2.65 min (YMC S5 ODS 4.6×50 mm, 10%-90% aqueous methanol over 4 minute gradient with 0.2% H3PO4, detecting at 220 nm).
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:11]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[C:10]([C:21]([O:23]CC)=[O:22])=[C:9]([CH3:26])[NH:8][N:7]=1)=[O:5])C.[OH-].[K+]>>[CH3:26][C:9]1[NH:8][N:7]=[C:6]([C:4]([OH:5])=[O:3])[CH:11]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[C:10]=1[C:21]([OH:23])=[O:22]
Reactant: CCOC(=O)C1=NNC(C)=C(C(=O)OCC)C1c1cccc([N+](=O)[O-])c1
Agent: [K+]
Agent: [OH-]
Product: CC1=C(C(=O)O)C(c2cccc([N+](=O)[O-])c2)C(C(=O)O)=NN1
Yield: 71 %

Procedure:
0.1 mol of 1,4-dihydro-6-methyl-4-(3-nitrophenyl)-pyridazine-3,5-dicarboxylic acid diethyl ester is saponified with 0.25 mol of KOH analogously to Example 28 to give 1,4-dihydro-6-methyl-4-(3-nitrophenyl)-pyridazine-3,5-dicarboxylic acid. Melting point 169° C. (decomposition).
Reaction SMILES: [BH3-]C#N.[Na+].C([OH:9])(C)(C)C.I[CH:11]([CH2:20][CH2:21][CH2:22][CH3:23])[CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O=O>O>[C:14]1([CH2:13][CH2:12][CH:11]([OH:9])[CH2:20][CH2:21][CH2:22][CH3:23])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: CCCCC(I)CCc1ccccc1
Reactant: CC(C)(C)O
Agent: O=O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: O
Product: CCCCC(O)CCc1ccccc1
Reaction time: 24 h
Yield: 55 %

Procedure:
A reaction vessel (30 ml, a two-neck, eggplant type flask) is subjected to nitrogen gas purging and NaBH3CN (0.5 mmol, 31.4 mg), Bu2(t-Bu)SnCl (0.0125 mmol, 4.1 mg, 3.5 μl) and tert-butanol (1 ml) are added. Then, 3-iodo-1-phenylheptane (0.25 mmol, 75.5 mg, 57.5 g 1) is added to the solution. The introduction of nitrogen gas is discontinued, a nitrogen gas-filled black butyl rubber balloon is set instead, and oxygen (0.375 mmol, 9 ml) is bubbled into the solution using a syringe. The reaction mixture is then incubated on an oil bath at 60° C. After 24 hours, heating is discontinued and the reaction mixture is diluted with pure water (10 ml) and extracted with ether (15 ml×4). The residue is purified by column chromatography (silica gel 2 g, ethyl acetate/hexane 20%) to provide 1-phenyl-3-heptanol (26.9 mg, 55%). 1H NMR revealed that the crude product comprised the alcohol/reduced compound/starting compound in a molar ratio of 56/28/16.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:21][C:22]([CH3:30])([CH3:29])[CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][CH2:11][CH2:12][NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N+:15]=1[O-].C1CCCCC=1>[Pd].CC(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:21][C:22]([CH3:29])([CH3:30])[CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][CH2:11][CH2:12][NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1
Reactant: CCOC(=O)CC(C)(C)Cc1ccc(OCCCNc2cccc[n+]2[O-])c(OC)c1
Agent: [Pd]
Solvent: CC(C)O
Solvent: C1=CCCCC1
Product: CCOC(=O)CC(C)(C)Cc1ccc(OCCCNc2ccccn2)c(OC)c1
Temperature: 25 °C
Yield: 84.3 %

Procedure:
A mixture of the product of STEP 7 (81.5 mg, 0.2mmol), 10% Pd/C (50 mg, 0.05 mmol), cyclohexene (0.5 ml, 4.9 mmol), and 2-propanol (5 ml) was heated at reflux for 3 h. The reaction was cooled to room temperature, filtered through a short column of Celite®, and washed with 2-propanol. The filtrate was concentrated to give 67.5 mg pale brown oil. The NMR spectra were consistent for the proposed structure.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[C:10]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[N:11][N:12]([C:17]3[C:18]([O:25][CH3:26])=[N:19][C:20]([O:23][CH3:24])=[N:21][CH:22]=3)[C:13]=2[CH:14]([CH3:16])[CH3:15])=[CH:4][CH:3]=1.[CH3:33][C:34]1[N:38]2[CH:39]=[C:40]([NH2:44])[CH:41]=[C:42]([CH3:43])[C:37]2=[N:36][N:35]=1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:44][C:40]2[CH:41]=[C:42]([CH3:43])[C:37]3[N:38]([C:34]([CH3:33])=[N:35][N:36]=3)[CH:39]=2)[C:9]2[C:10]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[N:11][N:12]([C:17]3[C:18]([O:25][CH3:26])=[N:19][C:20]([O:23][CH3:24])=[N:21][CH:22]=3)[C:13]=2[CH:14]([CH3:15])[CH3:16])=[CH:4][CH:3]=1
Reactant: CCOC(=O)c1nn(-c2cnc(OC)nc2OC)c(C(C)C)c1C(O)c1ccc(Cl)cc1
Reactant: Cc1cc(N)cn2c(C)nnc12
Product: CCOC(=O)c1nn(-c2cnc(OC)nc2OC)c(C(C)C)c1C(Nc1cc(C)c2nnc(C)n2c1)c1ccc(Cl)cc1

Procedure:
The title compound was prepared in analogy to the procedure described in Step 10.3 using ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-5-isopropyl-1H-pyrazole-3-carboxylate (Step 46.11) and 3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-amine (Step 67.4) overnight at RT. tR: 1.02 min (LC-MS 2); ESI-MS: 605 [M+H]+ (LC-MS 2).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8](I)[O:9][C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)=[CH:13][CH:12]=1)=[O:5])[CH3:2].CC1(C)C(C)(C)OB([C:39]2[CH:47]=[CH:46][CH:45]=[C:44]3[C:40]=2[CH:41]=[N:42][NH:43]3)O1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([C:39]2[CH:47]=[CH:46][CH:45]=[C:44]3[C:40]=2[CH:41]=[N:42][NH:43]3)[O:9][C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)=[CH:13][CH:12]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1nc(I)oc1-c1ccc(N2CCN(C(=O)OC(C)(C)C)CC2)cc1
Reactant: CC1(C)OB(c2cccc3[nH]ncc23)OC1(C)C
Agent: Cl[Pd]Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Solvent: CCO
Product: CCOC(=O)c1nc(-c2cccc3[nH]ncc23)oc1-c1ccc(N2CCN(C(=O)OC(C)(C)C)CC2)cc1
Temperature: 120 °C
Reaction time: 0.75 h
Yield: 46.7 %

Procedure:
To a mixture of tert-butyl 4-(4-(4-(ethoxycarbonyl)-2-iodooxazol-5-yl)phenyl)piperazine-1-carboxylate (0.080 g, 0.15 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-1H-indazole (0.080 g, 0.33 mmol) and sodium carbonate (0.048 g, 0.45 mmol) in toluene (0.81 ml), ethanol (0.49 ml) and water (0.23 ml) was added bis(triphenylphosphine)palladium (II) chloride (0.005 g, 0.007 mmol) and the resulting mixture heated in the microwave at 120° C. for 60 minutes followed by an additional 45 minutes. The reaction mixture was diluted with EtOAc and washed with 1M NaOH. The organic phase was passed through a MP-SH cartridge, dried over MgSO4 and the solvent removed in vacuo. The residue was purified by silica gel column chromatography using a 10-100% EtOAc in hexane gradient to afford tert-butyl 4-(4-(4-(ethoxycarbonyl)-2-(1H-indazol-4-yl)oxazol-5-yl)phenyl)piperazine-1-carboxylate (0.037 g, 0.07 mmol, 47%) as a yellow solid. LCMS (2) Rt: 3.57 min; m/z (ES+) 518.
Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([OH:8])[CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].C(N1[C:24](=[O:25])[C:23]2=[CH:26][CH:27]=[CH:28][CH:29]=[C:22]2[C:21]1=[O:30])(OCC)=O>O>[OH:8][C@H:5]1[CH2:6][CH2:7][C@H:2]([N:1]2[C:24](=[O:25])[C:23]3[C:22](=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:21]2=[O:30])[CH2:3][CH2:4]1
Reactant: CCOC(=O)N1C(=O)c2ccccc2C1=O
Reactant: N[C@H]1CC[C@H](O)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: O=C1c2ccccc2C(=O)N1[C@H]1CC[C@H](O)CC1
Reaction time: 16 h

Procedure:
Trans 4-aminocyclohexanol (25 g, 0.22 mol) dissolved in water (350 mL) was added potassium carbonate (3.0 g, 0.022 mol) and N-carbethoxyphthalimide (47.6 g, 0.22 mol) and the reaction mixture was stirred for 16 hours. The white precipitate was filtered off, washed with water and dried to give 37.7 g (71%) of trans-2-(4-hydroxycyclohexyl)-isoindole-1,3-dione (J. Med. Chem. 1996, 39, 314-322).
Reaction SMILES: ClCCCl.[N:5]([C:8]1[C:17]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([Cl:26])[CH:19]=2)=[N:16][C:15]([Br:27])=[CH:14][C:9]=1[C:10]([O:12][CH3:13])=[O:11])=[N+]=[N-]>ClCCl.CCCCCCCC(O)=O.CCCCCCCC(O)=O.CCCCCCCC(O)=O.CCCCCCCC(O)=O.[Rh].[Rh]>[Br:27][C:15]1[CH:14]=[C:9]([C:10]([O:12][CH3:13])=[O:11])[C:8]2[NH:5][C:23]3[CH:22]=[C:21]([O:24][CH3:25])[C:20]([Cl:26])=[CH:19][C:18]=3[C:17]=2[N:16]=1
Reactant: COC(=O)c1cc(Br)nc(-c2ccc(OC)c(Cl)c2)c1N=[N+]=[N-]
Agent: [Rh]
Solvent: ClCCl
Solvent: CCCCCCCC(=O)O
Solvent: ClCCCl
Product: COC(=O)c1cc(Br)nc2c1[nH]c1cc(OC)c(Cl)cc12
Temperature: 60 °C
Yield: 56 %

Procedure:
1,2-Dichloroethane (0.1 mL) was added to a mixture of methyl 3-azido-6-bromo-2-(3-chloro-4-methoxyphenyl)isonicotinate (56 mg, 0.14 mmol), rhodium octanoate dimer (11 mg, 0.014 mmol) and crushed 4 A° molecular sieves (56 mg) in a microwave vial. The vial was sealed and heated at 60° C. overnight. The reaction was diluted with dichloromethane, filtered, and the solvents removed from the filtrate. Radial silica gel chromatography (step gradient with hexane containing 50 to 100% methylene chloride) of the residue afforded methyl 2-bromo-8-chloro-7-methoxy-5H-pyrido[3,2-b]indole-4-carboxylate (29 mg). MS (ESI) m/z 370.9 (M+H). 1H NMR (CDCl3) δ ppm 9.51 (1H, br. s.), 8.31 (1H, s), 7.89 (1H, s), 6.99 (1H, s), 4.05 (3H, s), 4.01 (3H, s).
Reaction SMILES: [H-].[Na+].CN(C=O)C.[O:8]=[C:9]1[CH:18]=[C:17]([CH:19]=[O:20])[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10]1.[Cl:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26]Br)=[CH:24][CH:23]=1>C(OCC)(=O)C.O>[Cl:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26][N:10]2[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:17]([CH:19]=[O:20])=[CH:18][C:9]2=[O:8])=[CH:24][CH:23]=1
Reactant: O=Cc1cc(=O)[nH]c2ccccc12
Reactant: Clc1ccc(CBr)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: O=Cc1cc(=O)n(Cc2ccc(Cl)cc2)c2ccccc12
Reaction time: 0.5 h
Yield: 46.8 %

Procedure:
Sodium hydride (60% in oil) (1.3 g) was added at 0° C. to a DMF solution (50 ml) of 2-oxo-1,2-dihydroquinoline-4-carboxaldehyde (5.13 g), followed by stirring for 30 minutes. 4-chlorobenzylbromide (7.0 g) was added, and the resulting mixture was stirred at room temperature overnight. Water was added to the reaction mixture, extraction with ethyl acetate was performed, and the extract was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:10→1:4). The purified product was recrystallized from a chloroform-diisopropyl ether-n-hexane mixed solvent to thereby obtain 4.13 g (yield: 47%) of 1-(4-chlorobenzyl)-2-oxo-1,2-dihydroquinoline-4-carboxaldehyde as a white powder.
Reaction SMILES: CC1NC(C2C=C(C=CC=2C)C(O)=O)=C(C)N=1.I[C:19]1[NH:23][C:22]([CH:24]2[CH2:28][CH2:27][O:26][CH2:25]2)=[N:21][C:20]=1[CH3:29].IC1NC(C)=NC=1C.[CH3:38][C:39]1[CH:48]=[C:47]([CH3:49])[C:46](B2OC(C)(C)C(C)(C)O2)=[CH:45][C:40]=1[C:41]([O:43]C)=[O:42].CC1C=CC(C(OC)=O)=CC=1B1OC(C)(C)C(C)(C)O1>>[CH3:38][C:39]1[CH:48]=[C:47]([CH3:49])[C:46]([C:19]2[NH:23][C:22]([CH:24]3[CH2:28][CH2:27][O:26][CH2:25]3)=[N:21][C:20]=2[CH3:29])=[CH:45][C:40]=1[C:41]([OH:43])=[O:42]
Reactant: COC(=O)c1cc(B2OC(C)(C)C(C)(C)O2)c(C)cc1C
Reactant: Cc1nc(C2CCOC2)[nH]c1I
Agent: COC(=O)c1ccc(C)c(B2OC(C)(C)C(C)(C)O2)c1
Agent: Cc1nc(C)c(-c2cc(C(=O)O)ccc2C)[nH]1
Agent: Cc1nc(C)c(I)[nH]1
Product: Cc1cc(C)c(-c2[nH]c(C3CCOC3)nc2C)cc1C(=O)O

Procedure:
The title compound was prepared using standard chemical manipulations and procedures similar to those used for the preparation of compound 5.7, except 5-iodo-4-methyl-2-(tetrahydrofuran-3-yl)-1H-imidazole (compound 171.1) was used in place of 5-iodo-2,4-dimethyl-1H-imidazole (compound 5.5) and methyl 2,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (compound 160.1) was used in place of methyl 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (compound 5.4).
Reaction SMILES: [CH:1]1([NH:4][C@H:5]2[CH2:10][CH2:9][C@H:8]([C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)[CH2:7][CH2:6]2)[CH2:3][CH2:2]1.[F:17][C:18]([F:32])([F:31])[C@:19]([C:22]1[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=1)([OH:21])[CH3:20].CCN=C=NCCCN(C)C.C1C=NC2N(O)N=NC=2C=1.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH:1]1([N:4]([C@H:5]2[CH2:6][CH2:7][C@H:8]([C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)[CH2:9][CH2:10]2)[C:26](=[O:27])[C:25]2[CH:29]=[CH:30][C:22]([C@@:19]([OH:21])([CH3:20])[C:18]([F:17])([F:31])[F:32])=[CH:23][CH:24]=2)[CH2:2][CH2:3]1
Reactant: C[C@](O)(c1ccc(C(=O)O)cc1)C(F)(F)F
Reactant: c1cncc([C@H]2CC[C@H](NC3CC3)CC2)c1
Agent: CCN=C=NCCCN(C)C
Agent: O=C([O-])O
Agent: On1nnc2cccnc21
Solvent: CN(C)C=O
Product: C[C@](O)(c1ccc(C(=O)N(C2CC2)[C@H]2CC[C@H](c3cccnc3)CC2)cc1)C(F)(F)F
Temperature: 23 °C
Reaction time: 16 h

Procedure:
trans-N-cyclopropyl-4-(pyridine-3-yl)cyclohexylamine (7.3 g, 34.0 mmol, prepared as described above), (S)-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzoic acid (8.7 g, 37.3 mmol), EDCI (9.1 g, 47.6 mmol), HOAt (6.5 g, 47.6 mmol), and NaHCO3 (5.7 g, 68.0 mmol) were combined and dissolved in DMF (125 mL). After being stirred for 16 h at 23° C., the reaction was quenched with 1 M NaOH (150 mL) and diluted with EtOAc (300 mL). The aqueous layer was extracted with EtOAc (100 mL) and 10% MeOH/CH2Cl2 (5×100 mL) and the combined organic layers were washed with H2O (400 mL) and brine (400 mL), dried with MgSO4, filtered, and concentrated in vacuo. The crude material was purified by flash column chromatography (gradient elution, 3%→10% MeOH/CH2Cl2) to afford the product: 1H NMR (CDCl3, 500 MHz) δ 8.49 (s, 1H), 8.46 (d, J=3.6 Hz, 1H), 7.61 (d, J=8.1 Hz, 2H), 7.58 (d, J=7.7 Hz, 1H), 7.50 (d, J=8.3 Hz, 2H), 7.24 (dd, 1H-overlapping with CDCl3), 4.23 (m, 1H), 2.80 (m, 1H), 2.62 (m, 2H), 2.05 (m, 6H), 1.80 (s, 3H), 1.65 (m, 2H), 0.60 (d, J=4.8 Hz, 2H). 0.49 (m, 2H); MS(ESI) 433.3 [M+H]+; Anal. (C24H27 F3N2O2) C, H, N.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[C:11]([NH2:13])[NH:10][N:9]=2)=[CH:4][CH:3]=1.[CH2:14]([N:16]1[C:24]2[C:19](=[CH:20][C:21]([C:25](=O)[CH2:26][C:27](OCC)=[O:28])=[CH:22][CH:23]=2)[CH:18]=[N:17]1)[CH3:15].CC1C=CC(S(O)(=O)=O)=CC=1>C1(OC2C=CC=CC=2)C=CC=CC=1>[CH2:14]([N:16]1[C:24]2[C:19](=[CH:20][C:21]([C:25]3[NH:13][C:11]4[N:10]([N:9]=[C:8]([C:5]5[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=5)[N:12]=4)[C:27](=[O:28])[CH:26]=3)=[CH:22][CH:23]=2)[CH:18]=[N:17]1)[CH3:15]
Reactant: Nc1nc(-c2ccc(F)cc2)n[nH]1
Reactant: CCOC(=O)CC(=O)c1ccc2c(cnn2CC)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccc(Oc2ccccc2)cc1
Product: CCn1ncc2cc(-c3cc(=O)n4nc(-c5ccc(F)cc5)nc4[nH]3)ccc21
Reaction time: 2.5 h
Yield: 32.9 %

Procedure:
To a solution of 3-(4-fluorophenyl)-1H-1,2,4-triazol-5-amine (100 mg, 0.56 mmol) in diphenyl ether (1 ml) was added ethyl 3-(1-ethyl-1H-indazol-5-yl)-3-oxopropanoate (400 mg, 1.540 mmol) and TsOH (6 mg, 0.03 mmol), and the resulting mixture was strirred for 2.5 h at 170° C. The reaction mixture was then quenched by the addition of ethyl ether (8 ml). The solids were collected by filtration and washed with dichloromethane (5 ml) to afford 5-(1-ethyl-1H-indazol-5-yl)-2-(4-fluorophenyl)-[1,2,4]triazolo[1,5-α]pyrimidin-7(4H)-one as a light yellow solid (69 mg, 24%).
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:14](=[O:15])[C:13]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]4[C:24]([C:29]#[N:30])=[CH:25][CH:26]=[CH:27][CH:28]=4)=[CH:19][CH:18]=3)=[C:12]([CH2:31][CH2:32][CH3:33])[N:11]=[C:10]2[CH3:34])=[CH:5][CH:4]=1.B(Br)(Br)Br.C(OCC)(=O)C.O>C(Cl)Cl>[OH:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:14](=[O:15])[C:13]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]4[C:24]([C:29]#[N:30])=[CH:25][CH:26]=[CH:27][CH:28]=4)=[CH:19][CH:18]=3)=[C:12]([CH2:31][CH2:32][CH3:33])[N:11]=[C:10]2[CH3:34])=[CH:7][CH:8]=1
Reactant: CCCc1nc(C)n(-c2ccc(OC)cc2)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Agent: BrB(Br)Br
Solvent: CCOC(C)=O
Solvent: O
Solvent: ClCCl
Product: CCCc1nc(C)n(-c2ccc(O)cc2)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 106.9 %

Procedure:
To a solution of 4′-{[1-(4-methoxyphenyl)-2-methyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile (11.8 g) in methylene chloride (100 mL) was added boron tribromide (1.0 M methylene chloride solution, 50 mL), and the mixture was stirred at room temperature for 2 days. Ethyl acetate and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel column chromatography to give the title compound as a pale-yellow solid (12.22 g, 100%).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[CH:7][C:6]=1[OH:14])(=[O:3])[CH3:2].[K].[CH3:16][N:17]([CH3:22])[CH2:18][CH2:19][CH2:20]Cl.[OH-].[Na+]>O.CN(C)C=O>[CH3:16][N:17]([CH2:18][CH2:19][CH2:20][O:14][C:6]1[CH:7]=[CH:8][C:9]([N+:11]([O-:13])=[O:12])=[CH:10][C:5]=1[NH:4][C:1](=[O:3])[CH3:2])[CH3:22]
Reactant: CC(=O)Nc1cc([N+](=O)[O-])ccc1O
Reactant: CN(C)CCCCl
Agent: [K]
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)Nc1cc([N+](=O)[O-])ccc1OCCCN(C)C
Temperature: 60 °C

Procedure:
35.1 g (0.15 mol) of 2-acetylamino-4-nitrophenol, in the form of the potassium salt, are introduced into 105 ml of dimethylformamide and the mixture is then heated to 60° C., whilst stirring. 25.8 g (0.21 mol) of γ-dimethylaminopropyl chloride are then added; the reaction medium is heated at 90° C. for 210 minutes and is then poured into 750 g of iced water to which 40 ml of 1 N sodium hydroxide solution have been added. The expected product is extracted with methyl isobutyl ketone. After the methyl isobutyl ketone has been driven off in vacuo, the expected product is obtained in the form of an orange oil which crystallises rapidly (melting point: 69° C.).
Reaction SMILES: [C:1]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:33])[CH:15]([NH:22][S:23]([C:26]2[CH:31]=[CH:30][C:29]([I:32])=[CH:28][CH:27]=2)(=[O:25])=[O:24])[CH2:16][O:17]S(C)(=O)=O)=[CH:9][CH:8]=1)([O:3][CH2:4][CH3:5])=[O:2].[Cl:34][C:35]1[CH:36]=[C:37](O)[CH:38]=[CH:39][CH:40]=1>>[Cl:34][C:35]1[CH:40]=[C:39]([CH:38]=[CH:37][CH:36]=1)[O:17][CH2:16][CH:15]([NH:22][S:23]([C:26]1[CH:31]=[CH:30][C:29]([I:32])=[CH:28][CH:27]=1)(=[O:25])=[O:24])[C:14]([NH:13][C:10]1[CH:11]=[CH:12][C:7]([CH2:6][C:1]([O:3][CH2:4][CH3:5])=[O:2])=[CH:8][CH:9]=1)=[O:33]
Reactant: CCOC(=O)Cc1ccc(NC(=O)C(COS(C)(=O)=O)NS(=O)(=O)c2ccc(I)cc2)cc1
Reactant: Oc1cccc(Cl)c1
Product: CCOC(=O)Cc1ccc(NC(=O)C(COc2cccc(Cl)c2)NS(=O)(=O)c2ccc(I)cc2)cc1
Yield: 66.9 %

Procedure:
The procedure described in Example 125 was repeated, except that (RS)-N-(4-(carbethoxymethyl)phenyl)-2-(4-iodobenzenesulfonylamino)-3-methanesulfonyloxypropanamide (380 mg) was reacted with 3-chlorophenol (160 mg) to obtain (RS)-3-(3-chlorophenoxy)-N-(4-(ethoxycarbonylmethyl)phenyl)-2-(4-iodobenzenesulfonylamino)propanamide (267.88 mg).
Reaction SMILES: CO[C:3]([C:5]1[C:17](=[O:18])[N:16]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[N:15]2[C:7](=[CH:8][C:9]3[C:14]2=[CH:13][C:12]([C:27]([F:30])([F:29])[F:28])=[CH:11][CH:10]=3)[C:6]=1[OH:31])=[O:4].[NH2:32][CH2:33][C:34]([O-:36])=[O:35].[Na+]>COCCO>[F:26][C:23]1[CH:24]=[CH:25][C:20]([CH2:19][N:16]2[N:15]3[C:7](=[CH:8][C:9]4[C:14]3=[CH:13][C:12]([C:27]([F:28])([F:29])[F:30])=[CH:11][CH:10]=4)[C:6]([OH:31])=[C:5]([C:3]([NH:32][CH2:33][C:34]([OH:36])=[O:35])=[O:4])[C:17]2=[O:18])=[CH:21][CH:22]=1
Reactant: COC(=O)c1c(O)c2cc3ccc(C(F)(F)F)cc3n2n(Cc2ccc(F)cc2)c1=O
Reactant: NCC(=O)[O-]
Agent: [Na+]
Solvent: COCCO
Product: O=C(O)CNC(=O)c1c(O)c2cc3ccc(C(F)(F)F)cc3n2n(Cc2ccc(F)cc2)c1=O
Yield: 56.5 %

Procedure:
A mixture of 4-(4-fluoro-benzyl)-1-hydroxy-3-oxo-6-trifluoromethyl-3,4-dihydro-4,4a-diaza-fluorene-2-carboxylic acid methyl ester (100 mg, 0.23 mmol) and sodium glycinate (224 mg, 2.3 mmol) in 2-methoxyethanol (3.3 mL) was microwaved at 150° C. for 1 h and concentrated. Residue was dissolved in water (80 mL) and acidified to pH=3-4 using 1 N HCl solution. Precipitate was collected and rinsed with water. Solid was then dissolved in EtOAc, dried over MgSO4, filtered and concentrated. Crude product was triturated in MeOH (3 mL) and solid was collected and dried in vacuo to provide the title compound 62 mg. ESI (m/z): 476.01 (M−H)−
Reaction SMILES: [C:1]1([CH:7]([CH3:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:10]=[CH:11][CH3:12].B(F)(F)F>F>[CH:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:11]([CH3:12])[CH3:10])([CH3:9])[CH3:8]
Reactant: CC(C)c1ccccc1
Reactant: C=CC
Agent: F
Agent: FB(F)F
Product: CC(C)c1ccccc1C(C)C
Reaction time: 0.25 h
Yield: 41 %

Procedure:
12 g (0.1 mol) cumene is dissolved in 150 ml anhydrous hydrogen fluoride and while keeping the stirred solution at -20° C. to 0° C., 0.05 mol of propylene is introduced and stirring continued for 15 min. The reaction mixture is then saturated with boron trifluoride and stirring continued for another 15 min. After workup, 41% diisopropylbenzene was obtained, comprised of 99.6% of meta and 0.4% para isomer, together with about 15% 1,3,5-triisopropylbenzene, which can be recycled under conditions of Example 6 to produce more meta-diisopropylbenzene.
Reaction SMILES: Cl[C:2]1[C:3](=[O:18])[N:4]([CH:15]([CH3:17])[CH3:16])[S:5](=[O:14])(=[O:13])[C:6]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH2:19]([NH2:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CC#N>[CH2:19]([NH:26][C:2]1[C:3](=[O:18])[N:4]([CH:15]([CH3:17])[CH3:16])[S:5](=[O:14])(=[O:13])[C:6]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: CC(C)N1C(=O)C(Cl)=C(c2ccccc2)S1(=O)=O
Reactant: NCc1ccccc1
Solvent: CC#N
Product: CC(C)N1C(=O)C(NCc2ccccc2)=C(c2ccccc2)S1(=O)=O
Temperature: 120 °C
Yield: 58.1 %

Procedure:
4-Chloro-2-isopropyl-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.200 g, 0.70 mmol), benzylamine (0.082 g, 0.77 mmol) and TEA (0.078 g, 0.77 mmol) was dissolved in MeCN (3 ml) and heated at in a microwave reactor 120° C. for 5 mins. The reaction mixture was purified by silica gel column chromatography using a 75:25 mixture of heptane and EtOAc as eluant, to give the title compound (0.145 g, 58%). 1H NMR (500 MHz, CDCl3): δ 7.49-7.36 (m, 5H), 7.32-7.26 (m, 3H), 7.05-7.00 (m, 2H), 5.60-5.51 (m, 1H), 4.43 (hep, 1H), 4.08-4.02 (m, 2H), 1.61 (d, 6H); 13C NMR (125 MHz, CDCl3): δ 158.6, 136.5, 135.2, 131.7, 129.8, 129.0, 128.7, 128.1, 127.5, 124.8, 107.9, 48.3, 47.8, 20.3; Mass Spectrum: M−H+ 357.