Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[CH2:4][CH:3]([C:5]2[CH:6]=[CH:7][C:8]3[O:17][CH2:16][CH2:15][C:14]4[N:10]([N:11]=[C:12]([C:18]5[N:19]([CH:23]([CH3:25])[CH3:24])[N:20]=[CH:21][N:22]=5)[CH:13]=4)[C:9]=3[CH:26]=2)[CH2:2]1.C(N(CC)CC)C.[CH3:34][S:35](Cl)(=[O:37])=[O:36]>C(Cl)Cl>[CH:23]([N:19]1[C:18]([C:12]2[CH:13]=[C:14]3[N:10]([C:9]4[CH:26]=[C:5]([CH:3]5[CH2:2][N:1]([S:35]([CH3:34])(=[O:37])=[O:36])[CH2:4]5)[CH:6]=[CH:7][C:8]=4[O:17][CH2:16][CH2:15]3)[N:11]=2)=[N:22][CH:21]=[N:20]1)([CH3:24])[CH3:25]
Reactant: CC(C)n1ncnc1-c1cc2n(n1)-c1cc(C3CNC3)ccc1OCC2
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)n1ncnc1-c1cc2n(n1)-c1cc(C3CN(S(C)(=O)=O)C3)ccc1OCC2
Temperature: 0 °C
Yield: 63.9 %

Procedure:
An ice-cooled solution of 9-azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,10b-diaza-benzo[e]azulene (0.16 g, 0.46 mmol) in DCM (5 mL) was treated with triethylamine (0.14 mL, 1.0 mmol) then methanesulfonyl chloride (40 L, 0.51 mmol) and the mixture stirred at RT for 2 h. The reaction mixture was washed with water and the aqueous layer extracted with DCM, the combined organic extracts were combined, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 50 to 100% ethyl acetate in cyclohexane) to give 148 as a white solid (126 mg, 64%). 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J=2.49 Hz, 2 H); 7.31 (dd, J=8.35, 2.29 Hz, 1 H); 7.21 (d, J=8.32 Hz, 1 H); 6.89 (s, 1 H); 5.75-5.66 (m, 1 H); 4.56 (t, J=5.89 Hz, 2 H); 4.32 (t, J=8.24 Hz, 2 H); 4.12 (t, J=7.34 Hz, 2 H); 3.92-3.82 (m, 1 H); 3.20 (t, J=5.89 Hz, 2 H); 2.93 (s, 3 H); 1.62 (d, 6 H). LCMS: RT=9.68 min, M+H+=429
Reaction SMILES: [Br:1][C:2]1[CH:7]=[N:6][C:5](I)=[CH:4][N:3]=1.[C:9]([Si:11]([CH3:14])([CH3:13])[CH3:12])#[CH:10]>CN(C=O)C.CCN(CC)CC.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:1][C:2]1[CH:7]=[N:6][C:5]([C:10]#[C:9][Si:11]([CH3:14])([CH3:13])[CH3:12])=[CH:4][N:3]=1
Reactant: C#C[Si](C)(C)C
Reactant: Brc1cnc(I)cn1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: C[Si](C)(C)C#Cc1cnc(Br)cn1
Temperature: 25 °C
Reaction time: 16 h
Yield: 83.3 %

Procedure:
A mixture of 2-bromo-5-iodo-pyrazine (1.14 g, 4.0 mmol) and copper (I) iodide (80 mg, 0.42 mmol) in DMF/Et3N (2:1, 24 ml) was deoxygenated by evacuate/refill with nitrogen (×3). Ethynyl-trimethyl-silane (680 μl, 4.8 mmol) followed by Pd(PPh3)4 (230 mg, 0.2 mmol) were added and the mixture was deoxygenated again (×1). The reaction was stirred at RT for 16 hours, then partitioned between Et2O/H2O. The organic layer was washed with water (×1), brine (×1), then dried (MgSO4), filtered and evaporated. The residue was purified by chromatography on silica (2∝34% Et2O/Petrol) to give the title compound (850 mg, waxy solid) as ˜3:1 mixture of mono coupled product to bis coupled. 1H NMR (400 MHz, CDCl3): 8.63 (1H, d), 8.43 (1H, d), 0.25 (9H, s), [Bis coupled product: 8.60 (s), 0.25 (s)] This material was used without further purification.
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][Si](C(C)(C)C)(C)C)=[C:16]([CH2:28][CH:29]=[CH2:30])[CH:15]=3)[C:9]([CH2:11][CH3:12])=[N:10][C:5]2=[C:4]([CH3:31])[CH:3]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[CH3:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([OH:20])=[C:16]([CH2:28][CH:29]=[CH2:30])[CH:15]=3)[C:9]([CH2:11][CH3:12])=[N:10][C:5]2=[C:4]([CH3:31])[CH:3]=1
Reactant: C=CCc1cc(Cn2c(CC)nc3c(C)cc(C)nc32)ccc1O[Si](C)(C)C(C)(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: C=CCc1cc(Cn2c(CC)nc3c(C)cc(C)nc32)ccc1O
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
To a solution of 1.519 g (3.48 mmol) of the product of Step F in 8.0 mL of anhydrous THF was added 3.6 mL of a 1.0 M solution of tetra-n-butylammonium fluoride in THF and the reaction mixture was stirred for 2.5 hours at room temperature. The reaction mixture was then evaporated in vacuo and the residual oil was chromatographed on a silica gel flash chromatography column eluted with ethyl acetate. The purified fractions were combined, evaporated and dried in vacuo to afford the title compound.
Reaction SMILES: CC(C)([O-])C.[K+].[Cl:7][C:8]1[C:13]([F:14])=[CH:12][CH:11]=[C:10]([Cl:15])[C:9]=1[C:16](=[O:18])[CH3:17].[H][H]>CC(O)C>[Cl:7][C:8]1[C:13]([F:14])=[CH:12][CH:11]=[C:10]([Cl:15])[C:9]=1[C@@H:16]([OH:18])[CH3:17]
Reactant: CC(=O)c1c(Cl)ccc(F)c1Cl
Reactant: [H][H]
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(C)O
Product: C[C@H](O)c1c(Cl)ccc(F)c1Cl
Temperature: 40 °C
Reaction time: 21 h
Yield: 100 %

Procedure:
In an autoclave, 3.22 mg of RuBr2[(S,S)-xylskewphos](3,5-Me2pica) (3.39×10−3 mmol, S/C=1000) and 7.62 mg of potassium tert-butoxide (6.79×10−2 mmol) are placed, replaced with argon gas. Under argon gas flow, 0.5 mL of 2′,6′-dichloro-3′-fluoroacetophenone (3.39 mmol, from Jiangxi Jixiang Pharmachemical) and 2.9 mL of 2-propanol are added while measuring with syringe, pressurized with hydrogen to 10 atm., stirred at 40° C. for 21 hours, and the reduction of hydrogen pressure was confirmed and (S)-1-(2,6-dichloro-3-fluorophenyl)ethanol was obtained at 100% yield. The optical purity measured by HPLC (DAICEL CHRALPAK AD-RH, acetonitrile/water=25/75, 0.5 mL/min, 25° C., 220 nm, the retention time of each enantiomer: (S): 56.1 min, (R): 64.5 min) was 98.5% ee.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[O:10][CH3:11].Br[C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:21])[CH3:20])=[CH:15][C:14]=1[N+:22]([O-:24])=[O:23]>>[C:19]([C:16]1[CH:17]=[CH:18][C:13]([C:2]2[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=2[O:10][CH3:11])=[C:14]([N+:22]([O-:24])=[O:23])[CH:15]=1)(=[O:21])[CH3:20]
Reactant: COc1ccc(I)c(OC)c1
Reactant: CC(=O)c1ccc(Br)c([N+](=O)[O-])c1
Product: COc1ccc(-c2ccc(C(C)=O)cc2[N+](=O)[O-])c(OC)c1

Procedure:
By methods analogous to 2'described in Example 1 (a) and (b), 4-iodo-3-methoxy anisole and 4'-bromo-3'-nitroacetophenone were reacted to give the novel intermediate 4-acetyl-2',4'-dimethoxy-2-nitrobiphenyl, m.p. 129° - 131°C. which was converted to the novel intermediate 4acetyl-2-amino-2;40 ,4'-dimethoxybiphenyl, m.p. 149° - 151°C. This (15.7 g.) was diazotized and the diazonium solution added slowly to a solution of cuprous chloride (7.5 g.) in 4N hydrochloric acid (70 ml.) at 0°C. The mixture was warmed to room temperature over 1 hour and then heated for a further hour on a steam bath. The solution was cooled and made alkaline (pH14) with 18N caustic soda. The product was extracted with methylene chloride, the extract dried and the solvent evaporated off to give a brown oil which was extracted with ether. The ether was evaporated and the residual oil distilled and the distillate recrystallised from isopropanol to give the novel intermediate 4-acetyl-2-chloro-2',4'-dimethoxybiphenyl m.p. 115° - 118°C. By methods analogous to those described in Example 1 (d) and 1 (e) this was converted to crude 2-(2-chloro-2',4'-dimethoxy-4-biphenylyl)propionaldehyde and thence to the novel intermediate 2-(2-chloro-2',4'-dimethoxy-4-biphenylyl) propionic acid, obtained as an oil.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][CH:3]=1.O.[F-:13].[K+]>CC(C)=O>[I:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([F:13])(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: [F-]
Reactant: O=S(=O)(Cl)c1ccc(I)cc1
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Product: O=S(=O)(F)c1ccc(I)cc1

Procedure:
p-Iodobenzenesulfonyl chloride (593 g, 1.96 mol), prepared as described in Example 1(a) above, is dissolved in 2.5 L of acetone and placed in a 5 L three-neck round-bottom flask fitted with a heating mantle, mechanical stirring and a water-cooled condenser. Potassium fluoride (126 g, 2.17 mol) and about 25 mL of water is added and the reaction is heated at reflux for approximately 5 hours. On cooling, the reaction mass is filtered and the solvent removed to provide a crude solid, which on purification, by distillation under high vacuum, affords p-iodobenzenesulfonyl fluoride as a white solid; yield 504 g (90%).
Reaction SMILES: [CH3:1][N:2]=[C:3]=[O:4].[F:5][C:6]1[C:11]([C:12]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([C:23]4[CH:24]=[C:25]5[C:29](=[CH:30][CH:31]=4)[NH:28][N:27]=[CH:26]5)[CH:21]=3)[NH:16][CH:15]=2)=[O:13])=[C:10]([F:32])[CH:9]=[CH:8][C:7]=1[NH:33][S:34]([C:37]1[CH:42]=[C:41]([F:43])[CH:40]=[CH:39][C:38]=1[F:44])(=[O:36])=[O:35].C(=O)([O-])[O-].[K+].[K+].C(#N)C>O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][NH:2][C:3]([N:28]1[C:29]2[C:25](=[CH:24][C:23]([C:20]3[CH:21]=[C:22]4[C:14]([C:12](=[O:13])[C:11]5[C:10]([F:32])=[CH:9][CH:8]=[C:7]([NH:33][S:34]([C:37]6[CH:42]=[C:41]([F:43])[CH:40]=[CH:39][C:38]=6[F:44])(=[O:36])=[O:35])[C:6]=5[F:5])=[CH:15][NH:16][C:17]4=[N:18][CH:19]=3)=[CH:31][CH:30]=2)[CH:26]=[N:27]1)=[O:4]
Reactant: O=C(c1c(F)ccc(NS(=O)(=O)c2cc(F)ccc2F)c1F)c1c[nH]c2ncc(-c3ccc4[nH]ncc4c3)cc12
Reactant: CN=C=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CNC(=O)n1ncc2cc(-c3cnc4[nH]cc(C(=O)c5c(F)ccc(NS(=O)(=O)c6cc(F)ccc6F)c5F)c4c3)ccc21
Temperature: 140 °C
Yield: 72.5 %

Procedure:
Into a reaction flask, methyl isocyanate (6.5 mg, 0.11 mmol) is combined with N-{2,4-difluoro-3-[5-(1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-2,5-difluoro-benzenesulfonamide (P-0002, 22 mg, 0.031 mmol), tetrakis(triphenylphosphine)palladium(0) (2.2 mg, 0.0019 mmol), potassium carbonate (1.0 mL, 1.0 M in water) and 3 mL of acetonitrile. The reaction is heated at 140° C. for 50 minutes in a microwave, then diluted with water and ethyl acetate. The organic layer is washed with saturated sodium bicarbonate, then brine and dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with methanol and dichloromethane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (P-0003, 14 mg, 72%). MS (ESI) [M+H+]+=623.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH3:17])[CH2:6][CH2:5]1.Cl[C:19]1[CH:28]=[CH:27][C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]=1>Cl>[N:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:27]=[CH:28][C:19]=1[NH:1][CH2:2][CH2:3][N:4]1[CH2:5][CH2:6][N:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH3:17])[CH2:8][CH2:9]1
Reactant: COc1ccccc1N1CCN(CCN)CC1
Reactant: Clc1ccc2ccccc2n1
Agent: Cl
Product: COc1ccccc1N1CCN(CCNc2ccc3ccccc3n2)CC1
Reaction time: 18 h
Yield: 12.4 %

Procedure:
1-(2-aminoethyl)-4-(2-methoxyphenyl)piperazine (9.4 g, 40 mmol) and 2-chloroquinoline (6.5 g, 40 mmol) were heated at 160° C. for 3 h, then at 120° C. for 18 h in a sealed vessel. The resultant brown tar was taken up into dilute hydrochloric acid (300 ml), washed with dichloromethane (3×100 ml) basified with sodium hydroxide, extracted into dichloromethane (3×100 ml), dried (MgSO4) then evaporated in vacuo to give a brown oil. The oil was purified by chromatography [alumina; ethyl acetate-toluene (1:4)] to give the product (1.8 g) as a clear oil.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([CH:12]=[C:13]([C:15]([CH3:22])([CH3:21])[C:16]([O:18][CH2:19][CH3:20])=[O:17])[N:14]=2)[N:11]=1.[C:23]1([CH:29]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[N:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C>[C:36]1([CH:29]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:30]2[CH2:31][CH2:32][N:33]([CH2:2][CH2:3][CH2:4][CH2:5][C:6]3[CH:7]=[CH:8][C:9]4[N:10]([CH:12]=[C:13]([C:15]([CH3:22])([CH3:21])[C:16]([O:18][CH2:19][CH3:20])=[O:17])[N:14]=4)[N:11]=3)[CH2:34][CH2:35]2)[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1
Reactant: c1ccc(C(c2ccccc2)N2CCNCC2)cc1
Reactant: CCOC(=O)C(C)(C)c1cn2nc(CCCCCl)ccc2n1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)C(C)(C)c1cn2nc(CCCCN3CCN(C(c4ccccc4)c4ccccc4)CC3)ccc2n1
Temperature: 60 °C
Reaction time: 5 h
Yield: 36.1 %

Procedure:
921 mg of ethyl 2-[6-(4-chlorobutyl)imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate was dissolved in 10 ml of N,N-dimethylformamide; 789 mg of 1-(diphenylmethyl)piperazine, 433 mg of potassium iodide and 520 mg of potassium carbonate were added, followed by stirring at 60° C. for 5 hours. After cooling, ethyl acetate was added; the mixture was washed with saturated saline, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate:triethylamine (50:1). The desired fraction was collected, concentrated under reduced pressure and crystallized from ethyl ether-hexane (1:1), collected by filtration, washed with hexane and dried to yield 554 mg of the title compound.
Reaction SMILES: [CH3:1][O:2][C@H:3]1[C@H:9]([CH3:10])[O:8][C@@H:6]([OH:7])[CH2:5][C@H:4]1[NH:11][C:12](=[O:17])[C:13]([F:16])([F:15])[F:14].[N+:18]([C:21]1[CH:29]=[CH:28][C:24]([C:25](Cl)=[O:26])=[CH:23][CH:22]=1)([O-:20])=[O:19].O.CC(C)=O>N1C=CC=CC=1>[CH3:1][O:2][C@H:3]1[C@H:9]([CH3:10])[O:8][CH:6]([O:7][C:25](=[O:26])[C:24]2[CH:23]=[CH:22][C:21]([N+:18]([O-:20])=[O:19])=[CH:29][CH:28]=2)[CH2:5][C@H:4]1[NH:11][C:12](=[O:17])[C:13]([F:16])([F:15])[F:14]
Reactant: CO[C@H]1[C@H](C)O[C@@H](O)C[C@H]1NC(=O)C(F)(F)F
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Solvent: c1ccncc1
Solvent: O
Solvent: CC(C)=O
Product: CO[C@H]1[C@H](C)OC(OC(=O)c2ccc([N+](=O)[O-])cc2)C[C@H]1NC(=O)C(F)(F)F
Reaction time: 0.5 h
Yield: 67.9 %

Procedure:
A solution of 1.64 g; 6.38 mmol of compound VII in 76 ml of anhydrous pyridine was treated at 0° C. under stirring with 2 g of p-nitrobenzoyl chloride. After 30 minutes at 0° C. and then 20 hours at room temperature, the reaction mixture was poured into iced water and extracted with chloroform; the combined chloroform extracts were washed successively with a 10% potassium bisulphate solution, 10% sodium bicarbonate solution and finally with water, after which it was dried over anhydrous sodium sulphate and then concentrated to a residue. The residue was chromatographed on a silica gel column. Elution with a chloroform: acetone mixture (95:5 by volume) gave 1.76 g (yield 68%) of 4-O-methyl-1-O-p-nitrobenzoyl-2,3,6-trideoxy-3-trifluoroacetamido-L-ribohexopyranose (VIII).
Reaction SMILES: [CH3:1][C:2]([N:5]1[C:9]2[N:10]=[C:11]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[CH:12]=[C:13]([C:14]([O:16]CC)=[O:15])[C:8]=2[C:7]([CH3:27])=[N:6]1)([CH3:4])[CH3:3].[OH-].[Na+]>CCO>[CH3:4][C:2]([N:5]1[C:9]2[N:10]=[C:11]([C:19]3[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=3)[CH:12]=[C:13]([C:14]([OH:16])=[O:15])[C:8]=2[C:7]([CH3:27])=[N:6]1)([CH3:1])[CH3:3]
Reactant: CCOC(=O)c1cc(-c2ccc(OC)cc2)nc2c1c(C)nn2C(C)(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: COc1ccc(-c2cc(C(=O)O)c3c(C)nn(C(C)(C)C)c3n2)cc1

Procedure:
The title compound was prepared in the same manner as described for intermediate 75 using ethyl 1-(1,1-dimethylethyl)-3-methyl-6-[4-(methyloxy)phenyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylate (400 mg, 1.089 mmol), 3N sodium hydroxide (1.814 mL, 5.44 mmol), and EtOH (6 mL). The product was collected as 347 mg (94%). LCMS E-S (M+H)=340.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.81 (s, 9H), 2.55 (s, 3H), 7.11 (d, J=8.84 Hz, 2H), 7.89 (s, 1H), 8.16 (d, J=8.84 Hz, 2H).
Reaction SMILES: [CH:1]([C:3]1[O:7][C:6]([S:8]([OH:11])(=[O:10])=[O:9])=[CH:5][CH:4]=1)=O.[Na].[CH2:13]([NH:20][OH:21])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>>[CH2:13]([N+:20]([O-:21])=[CH:1][C:3]1[O:7][C:6]([S:8]([OH:11])(=[O:10])=[O:9])=[CH:5][CH:4]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=Cc1ccc(S(=O)(=O)O)o1
Reactant: ONCc1ccccc1
Agent: [Na]
Product: O=S(=O)(O)c1ccc(C=[N+]([O-])Cc2ccccc2)o1
Yield: 82 %

Procedure:
Following the procedure of Example 1 above and using 5-formylfuran-2-sulfonic acid, sodium salt hydrate and N-benzylhydroxylamine, the title compound was prepared in 82% yield as the sodium salt, m.p. 223.7° C. (dec.).
Reaction SMILES: S([C:5]1[CH:11]=[CH:10][C:8]([CH3:9])=[CH:7][CH:6]=1)([O-])(=O)=O.[CH2:12]([CH:14]1[O:16][CH2:15]1)Cl>>[C:8]([C:5]1[CH:11]=[CH:10][C:8]([CH2:9][CH2:12][CH:14]2[O:16][CH2:15]2)=[CH:7][CH:6]=1)([CH3:10])([CH3:9])[CH3:7]
Reactant: Cc1ccc(S(=O)(=O)[O-])cc1
Reactant: ClCC1CO1
Product: CC(C)(C)c1ccc(CCC2CO2)cc1

Procedure:
reacting a 4-tert.butylbenzyl magnesuim halide with a stereochemically pure glycydyl tosylate or epichlorohydrin to form a single enantiomer of 4-(4'-tert.butylphenyl)-1,2-epoxybutane;
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].C(O[C:10]([CH:12]1[C:17](=[O:18])[CH2:16][CH2:15][N:14]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:13]1)=O)C.[CH2:26](I)[CH2:27][CH2:28]C>CC(C)=O>[CH2:19]([N:14]1[CH2:15][CH2:16][C:17](=[O:18])[CH:12]([CH2:10][CH2:26][CH2:27][CH3:28])[CH2:13]1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: CCOC(=O)C1CN(Cc2ccccc2)CCC1=O
Reactant: CCCCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCCC1CN(Cc2ccccc2)CCC1=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 68.2 %

Procedure:
To a suspension of anhydrous potassium carbonate (22.8 g) and 1-benzyl-4-oxo-piperidine-3-carboxylic acid ethyl ester (10 g) in acetone (125 ml) was added a solution of butyl iodide (13.4 g, 8.3 ml) in acetone (50 ml) under argon over a period of 30 minutes. The resulting suspension was stirred at RT for 30 min and then refluxed for 12 hours. The suspension was cooled, filtered and concentrated in vacuo. The residue was dissolved in DCM and the solution was washed with water and brine, dried over Na2SO4 and evaporated. To the residue was added aqueous HCl (20%, 100 ml) and the solution was refluxed for 24 hours. The solution was evaporated and the residue was dissolved in DCM, washed with 10% aq. Na2CO3 solution and brine, dried and evaporated. The crude product was purified by flash chromatography (ethyl acetate/hexanes 1:2) to give the product as a slightly yellow oil (6.4 g). MS (ESI): 246.4 (MH+).
Reaction SMILES: [OH-].[Na+].[NH2:3][C:4]1[CH:24]=[CH:23][C:7]([C:8]([C:10]2[N:14]3[CH:15]=[C:16]([C:19]([O:21]C)=[O:20])[CH:17]=[CH:18][C:13]3=[CH:12][N:11]=2)=[O:9])=[CH:6][C:5]=1[O:25][CH3:26].O1CCOCC1.ClCCl>CO>[NH2:3][C:4]1[CH:24]=[CH:23][C:7]([C:8]([C:10]2[N:14]3[CH:15]=[C:16]([C:19]([OH:21])=[O:20])[CH:17]=[CH:18][C:13]3=[CH:12][N:11]=2)=[O:9])=[CH:6][C:5]=1[O:25][CH3:26]
Reactant: COC(=O)c1ccc2cnc(C(=O)c3ccc(N)c(OC)c3)n2c1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: C1COCCO1
Solvent: CO
Product: COc1cc(C(=O)c2ncc3ccc(C(=O)O)cn23)ccc1N
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1.51 ml (1.51 mmol) of a 1N aqueous sodium hydroxide solution are added to 300 mg (0.92 mmol) of methyl 3-(4-amino-3-methoxybenzoyl)imidazo[1,5-a]pyridine-6-carboxylate obtained in example 83 in 15 ml of a mixture (5/5/5) of dioxane, dichloromethane and methanol. The reaction medium is stirred at ambient temperature overnight and then concentrated under reduced pressure. The residue is dissolved in water, washing is carried out with ethyl acetate and then the aqueous phase is acidified with 1.5 ml of 1N hydrochloric acid. The precipitate formed is filtered off, washed with water and then dried. 346 mg of a yellow solid are collected, which solid is salified in the sodium salt.0.7H2O form. Melting point: 306° C.; 1H NMR (d6-DMSO): 3.87 (3H, s), 6.72 (1H, d), 7.70-7.78 (3H, m), 7.96 (1H, s), 8.18 (1H, d), 10.09 (1H, s)
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[C:5]([CH:7]1[CH2:12][CH2:11][N:10]([CH3:13])[CH2:9][CH2:8]1)=[O:6].[C:17]1([N:23]=[C:24]=[S:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[C:17]1([NH:23][C:24](=[S:25])[NH:1][C:2]2[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=2)[C:5]([CH:7]2[CH2:8][CH2:9][N:10]([CH3:13])[CH2:11][CH2:12]2)=[O:6])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: S=C=Nc1ccccc1
Reactant: CN1CCC(C(=O)c2cccc(N)c2)CC1
Product: CN1CCC(C(=O)c2cccc(NC(=S)Nc3ccccc3)c2)CC1
Yield: 99.6 %

Procedure:
Beginning with 4-[3-aminobenzoyl]-1-methylpiperidine (25 mg, 0.115 mmol) and phenyl isothiocyanate (82 μL, 0.688 mmol), 40.5 mg (100%) of the title compound were recovered.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH:10]([OH:27])[C@@H:11]([NH:16]C(OCC1C=CC=CC=1)=O)[CH2:12][CH:13]([CH3:15])[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:28]>CO.[Pd]>[ClH:28].[CH2:1]([O:8][CH2:9][CH:10]([OH:27])[C@@H:11]([NH2:16])[CH2:12][CH:13]([CH3:14])[CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)C[C@H](NC(=O)OCc1ccccc1)C(O)COCc1ccccc1
Agent: [Pd]
Agent: Cl
Solvent: CO
Product: CC(C)C[C@H](N)C(O)COCc1ccccc1

Procedure:
A mixture of 100 mg of (3S)-3-carbobenzoxyamino-5-methyl-1,2-epoxyhexane, 2 g of dry silica gel and 2 ml of benzyl alcohol was heated at 100° C. for 16 hours. After filtration of the silica gel, the filtrate was evaporated under reduced pressure to obtain 105 mg of (2RS, 3S)-3-carbobenzoxyamino-2-hydroxy-5-methylhexyl benzyl ether as a colorless oil. To a solution of 86 mg of the ether obtained in 10 ml of methanol was added 0.14 ml of a 2N-hydrochloric acid, and the mixture was hydrogenated over 17 mg of palladium charcoal under hydrogen atmosphere. After filtration of the catalyst, the filtrate was evaporated under reduced pressure. The residue was purified by preparative silica gel thin layer chromatography (developing solvent: lower layer of chloroform/methanol/water=8/3/1 by volume) to obtain 17 mg of (2RS, 3S)-3-amino-2-hydroxy-5-methylhexyl benzyl ether hydrochloride as a colorless viscous oil.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH2:10][CH:11]([O:17][CH:18]([CH3:20])[CH3:19])[C:12]([O:14]CC)=[O:13])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[CH3:21][C:22]1[S:23][CH:24]=[C:25]([C:27]2[S:31][C:30]([S:32](Cl)(=[O:34])=[O:33])=[CH:29][CH:28]=2)[N:26]=1.C(N(CC)CC)C.C(OCC)(=O)C>ClCCl>[CH:18]([O:17][CH:11]([CH2:10][C:4]1[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([O:1][S:32]([C:30]2[S:31][C:27]([C:25]3[N:26]=[C:22]([CH3:21])[S:23][CH:24]=3)=[CH:28][CH:29]=2)(=[O:33])=[O:34])[CH:3]=1)[C:12]([OH:14])=[O:13])([CH3:19])[CH3:20]
Reactant: Cc1nc(-c2ccc(S(=O)(=O)Cl)s2)cs1
Reactant: CCOC(=O)C(Cc1ccc(OC)c(O)c1)OC(C)C
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: COc1ccc(CC(OC(C)C)C(=O)O)cc1OS(=O)(=O)c1ccc(-c2csc(C)n2)s1
Reaction time: 8 h
Yield: 21.9 %

Procedure:
15 mg of Ethyl 3-(3-hydroxy-4-methoxyphenyl)-2-isopropoxypropanoate and 25 mg of 5-(2-methyl-1,3-thiazol-4-yl)-2-thiophenesulfonyl chloride were dissolved in 0.4 ml of dichloromethane, and 50 μl of triethylamine was added, and the mixture was kept still at room temperature overnight. To the reaction mixture was added ethyl acetate and the mixture was washed with water. The solvent was concentrated, and the residue was treated with 0.4 ml of ethanol and 0.1 ml of 5N-sodium hydroxide, and the mixture was kept still at room temperature for 30 minutes. The reaction mixture was neutralized with 1N-hydrochloric acid, extracted with ethyl acetate. The solvent was distilled off, and the residue was purified by reverse-phase high performance liquid chromatography, to give 5.8 mg of the title compound.