Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([O:6][CH:7]([O:10][C:11]2[CH2:15][CH2:14][CH2:13][CH:12]=2)[CH2:8][OH:9])[CH2:5][CH2:4][CH2:3][CH:2]=1.[C:16](OC)(=[O:20])[C:17]([CH3:19])=[CH2:18].O>[OH-].[Li+].COC1C=CC(O)=CC=1.CO>[C:16]([O:9][CH2:8][CH:7]([O:6][C:1]1[CH2:5][CH2:4][CH2:3][CH:2]=1)[O:10][C:11]1[CH2:15][CH2:14][CH2:13][CH:12]=1)(=[O:20])[C:17]([CH3:19])=[CH2:18]
Reactant: OCC(OC1=CCCC1)OC1=CCCC1
Reactant: C=C(C)C(=O)OC
Agent: COc1ccc(O)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: C=C(C)C(=O)OCC(OC1=CCCC1)OC1=CCCC1
Yield: 84.7 %

Procedure:
In a 3000-liter reactor equipped with a stirrer, a thermometer, an air introducing pipe, a distillation column and a reflux condenser, 776 kg (4 kmoles) of dicyclopentenyloxyethyl alcohol, and 1200 kg (12 kmoles) of methyl methacrylate were placed and mixed well with stirring. The water content of the resulting mixture was 800 ppm. The water content was measured by using a Karl Fischer type digital microamount water content measuring device (mfd. by Mitsubishi Chemical Industries Ltd.). Subsequently, 3 kg of anhydrous lithium hydroxide as a catalyst and 390 g of hydroquinone monomethyl ether as a polymerization inhibitor were added to the reactor, and the reaction was carried out while introducing dried air at a rate of 4 m3/ hr and refluxing the methyl methacrylate through the distillation column. While removing methanol by-produced by the reaction from the distillation column, the reaction was continued until almost no methanol was distilled (about 8 hours), followed by removal of unreacted methyl methacrylate under reduced pressure. After cooling, the reaction solution was filtered under pressure (5 kg/cm2) using a filter paper (pore size 0.1 mm, area 5 m2) placing thereon 10 kg of diatomaceous earth to yield 943 kg of dicyclopentenyloxyethyl methacrylate. The filtering time was 2.5 hours.
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][CH2:13][N:14]3[CH2:23][CH2:22][C:17]4([CH2:20][CH:19]([OH:21])[CH2:18]4)[CH2:16][CH2:15]3)[N:8]2[CH3:11])=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[N:3]=1.[CH2:30]([C:32]1[NH:33][C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1)[CH3:31].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:30]([C:32]1[N:33]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[C:7]([CH2:12][CH2:13][N:14]4[CH2:15][CH2:16][C:17]5([CH2:20][CH:19]([OH:21])[CH2:18]5)[CH2:22][CH2:23]4)[N:8]3[CH3:11])=[C:4]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[N:3]=2)[C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1)[CH3:31]
Reactant: Cn1c(CCN2CCC3(CC2)CC(O)C3)nc2c(N3CCOCC3)nc(Cl)nc21
Reactant: CCc1nc2ccccc2[nH]1
Agent: [Pd]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CCN3CCC4(CC3)CC(O)C4)n(C)c2n1
Temperature: 120 °C
Yield: 44 %

Procedure:
A mixture of 7-[2-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)ethyl]-7-azaspiro[3.5]nonan-2-ol (75 mg, 0.18 mmol), 2-ethylbenzimidazole (29 mg, 0.20 mmol), Pd2(dba)3 (4.1 mg, 2.5 mol %), Xphos (8.5 mg, 10 mol %) and Cs2CO3 (87 mg, 0.27 mmol) in dioxane (2.0 mL) was purged with argon gas then heated at 120° C., for 18 h, in a sealed tube. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then the desired product eluted with 2 M NH3 in MeOH. The resulting residue was purified by flash chromatography (Si—PCC, 0-10% 2 M NH3/MeOH in DCM) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient of acetonitrile 20-98%) to give 465 (42 mg, 44%) as an off white solid. LCMS: (Method I): RT 2.47 min; [M+H]+ 531.3. 1H NMR (400 MHz, CHCl3-d): δ 8.01-7.96 (m, 1H), 7.76-7.72 (m, 1 H), 7.28-7.22 (m, 2 H), 4.37-4.27 (m, 5 H), 3.86 (t, J=4.7 Hz, 4 H), 3.78 (s, 3 H), 3.34 (q, J=7.5 Hz, 2 H), 3.17-3.02 (m, 2 H), 2.99-2.81 (m, 2 H), 2.71-2.39 (m, 4 H), 2.31-2.24 (m, 2 H), 1.74-1.64 (m, 6 H), 1.44 (t, J=7.5 Hz, 3 H)
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([NH:13][CH2:14][CH3:15])[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].CC1(C)C(C)(C)OB([C:24]2[CH:36]=[CH:35][C:27]([CH2:28][N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[CH:26][CH:25]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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>[CH2:14]([NH:13][C:4]1[C:5]([CH3:12])=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:11]=[C:2]([C:24]2[CH:25]=[CH:26][C:27]([CH2:28][N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[CH:35][CH:36]=2)[CH:3]=1)[CH3:15]
Reactant: CC1(C)OB(c2ccc(CN3CCOCC3)cc2)OC1(C)C
Reactant: CCNc1cc(Br)cc(C(=O)OC)c1C
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: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: CCNc1cc(-c2ccc(CN3CCOCC3)cc2)cc(C(=O)OC)c1C
Temperature: 100 °C
Yield: 98.7 %

Procedure:
To a stirred solution of methyl 5-bromo-3-(ethylamino)-2-methylbenzoate (600 mg, 2.2 mmol) and 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]morpholine (1.0 g, 3.3 mmol) in dioxane (5 mL), aqueous 2M Na2CO3 solution (3.96 mL, 7.93 mmol) was added and solution was purged with argon for 15 min. Then Pd(PPh3)4 (255 mg, 0.22 mmol) was added and argon was purged again for 15 min. Reaction mass was heated at 100° C. for 4 h. On completion, reaction mixture was diluted with water and extracted with 10% MeOH/DCM (3 times). Combined organic layer was dried over sodium sulphate. Removal of the solvent under reduced pressure followed by column chromatographic purification afforded the desired compound (800 mg, 98%).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([CH3:22])([CH3:21])[C:14]([N:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[O:15])[CH:11]=2)[NH:6][C:5]=1[C:23]1[CH:28]=[C:27]([CH3:29])[CH:26]=[C:25]([CH3:30])[CH:24]=1.[N:31]1[CH:36]=[CH:35][C:34]([CH2:37][CH2:38][CH2:39][CH:40]=O)=[CH:33][CH:32]=1.S([O-])([O-])(=O)=O.[Mg+2].[BH4-].[Na+].[NH4+].[OH-]>CO>[CH3:30][C:25]1[CH:24]=[C:23]([C:5]2[NH:6][C:7]3[C:12]([C:4]=2[CH2:3][CH2:2][NH:1][CH2:40][CH2:39][CH2:38][CH2:37][C:34]2[CH:35]=[CH:36][N:31]=[CH:32][CH:33]=2)=[CH:11][C:10]([C:13]([CH3:22])([CH3:21])[C:14]([N:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[O:15])=[CH:9][CH:8]=3)[CH:28]=[C:27]([CH3:29])[CH:26]=1
Reactant: O=CCCCc1ccncc1
Reactant: CCN(CC)C(=O)C(C)(C)c1ccc2[nH]c(-c3cc(C)cc(C)c3)c(CCN)c2c1
Agent: O=S(=O)([O-])[O-]
Agent: [BH4-]
Agent: [Mg+2]
Solvent: CO
Product: CCN(CC)C(=O)C(C)(C)c1ccc2[nH]c(-c3cc(C)cc(C)c3)c(CCNCCCCc3ccncc3)c2c1
Temperature: -10 °C
Reaction time: 1 h

Procedure:
A mixture of 93.3 mg (0.23 mmol) of 2-[3-(2-aminoethyl)-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-N,N-diethylisobutyramide, 37.7 mg (0.253 mmol) of 4-(pyridin-4-yl)butyraldehyde, and 138 mg (1.15 mmol) of magnesium sulfate was purged with nitrogen and cooled in an ice-methanol bath at about -10° C. as 0.50 mL of CDCl3 was added gradually by syringe. The mixture was stirred under nitrogen at this temperature for 1 hour. The septum was removed just long enough to add 11.3 mg (0.30 mmol) of sodium borohydride, and the solution was repurged with nitrogen. The mixture was stirred at -10° to -5° C. as 0.50 mL of dry methanol was added gradually, and stirring was continued at this temperature. After 35 minutes, the mixture was partitioned between 5 mL of ethyl acetate and 5 mL of water. The ethyl acetate layer was washed with brine, then dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by two stages of preparative TLC on Analtech tapered silica gel GF plates (developed first in 90:10:1 methylene chloride -methanol-ammonium hydroxide and repeated in 90:10 methylene chloride -methanol). Isolation of the product bands gave 25.7 mg (21%) of light golden-colored glassy residue; virtually homogenous by TLC in 92.5:7.5:0.75 CH2Cl2 -MeOH-concd. NH4OH. 500 MHz 1H NMR (CDCl3) was consistent with the assigned structure. Mass spectrum (ESI): m/e=539 (M+H).
Reaction SMILES: I[Si](C)(C)C.[OH:6][C:7]1[CH:8]=[C:9]([CH:19]=[C:20]([O:22][C@H:23]([CH3:27])[CH2:24][O:25]C)[CH:21]=1)[C:10]([NH:12][C:13]1[CH:17]=[CH:16][N:15]([CH3:18])[N:14]=1)=[O:11].C(=O)([O-])[O-].[K+].[K+].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(#N)C.CO>[OH:6][C:7]1[CH:8]=[C:9]([CH:19]=[C:20]([O:22][C@H:23]([CH3:27])[CH2:24][OH:25])[CH:21]=1)[C:10]([NH:12][C:13]1[CH:17]=[CH:16][N:15]([CH3:18])[N:14]=1)=[O:11]
Reactant: COC[C@@H](C)Oc1cc(O)cc(C(=O)Nc2ccn(C)n2)c1
Agent: C[Si](C)(C)I
Agent: O=C([O-])[O-]
Agent: O=S([O-])([O-])=S
Solvent: CO
Solvent: CC#N
Product: C[C@H](CO)Oc1cc(O)cc(C(=O)Nc2ccn(C)n2)c1
Reaction time: 0.5 h
Yield: 64 %

Procedure:
Iodotrimethylsilane (6.64 mL, 47 mmol) was added to a solution of 3-hydroxy-5-[(1R)-2-methoxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide (2.86 g, 9.38 mmol) in acetonitrile (120 mL) and the resultant mixture stirred for 24 hours. Methanol (30 mL) was added and the mixture stirred for 30 minutes, saturated potassium carbonate (30 mL) and saturated sodium thiosulphate (30 mL) were then added and the mixture stirred for 20 mins. The acetonitrile was removed in vacuo and water (50 mL) added. The mixture was adjusted to pH4 with 1M hydrochloric acid, extracted into ethyl acetate (3×100 mL) and the combined extracts washed with brine (50 mL), dried (MgSO4) and evaporated to a residue which was chromatographed on silica, eluting with a gradient of 0-50% methanol in ethyl acetate, to give the desired compound (1.75 g).
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[CH3:9].Cl.[N:11]([O-])=O.[Na+].[F:15][B-:16]([F:19])([F:18])[F:17].[Na+]>O>[F:15][B-:16]([F:19])([F:18])[F:17].[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([N+:6]#[N:11])=[CH:4][C:3]=1[CH3:9]
Reactant: Cc1cc(N)ccc1Cl
Reactant: O=N[O-]
Agent: Cl
Agent: F[B-](F)(F)F
Agent: [Na+]
Solvent: O
Product: Cc1cc([N+]#N)ccc1Cl
Yield: 95.2 %

Procedure:
Synthesized according to General Procedure 1. 4-chloro-3-methylaniline (5 g, 35.3 mmol) in water (15 mL) and conc. HCl (9.5 mL, 116.5 mmol) at −5° C. was added a freshly prepared aqueous solution of sodium nitrite (3.2 g, 45.9 mmol) in water (8 mL) slowly over 10 minutes. After stirring for 15 minutes at −5° C. a freshly prepared aqueous solution of sodium tetrafluoroborate (5.4 g, 49.4 mmol) in water (14 mL) was added in one portion causing the formation of a precipitate. The solid was filtered and washed with cold (5° C.) diethyl ether (10 mL). The solid was dissolved in acetone (15 mL) and filtered. To the filtrate was added diethyl ether (15 mL) causing the precipitation of the arenediazonium tetrafluoroborate. The solid was filtered, washed with cold (5° C.) diethyl ether (5 mL) and then air dried overnight to provide 4-chloro-3-methylbenzenediazonium tetrafluoroborate (8.07 g, 33.6 mmol, 95% yield) as a tan solid. 1H-NMR (400 MHz, DMSO-d6) δ 8.68 (d, J=2.2 Hz, 1H), 8.56 (dd, J=2.4, 8.8 Hz, 1H), 8.10 (d, J=8.8 Hz, 1H) and 3.47 (s, 3H) ppm. LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA), m/z: M+1 obs=125.0; tR=0.24 min.
Reaction SMILES: [CH:1]1[C:6]([C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=2)=[CH:5][CH:4]=[C:3](O)[CH:2]=1.C(OC1C=CC(C(Cl)=O)=CC=1)CCCCCCC.[CH2:33]([O:41][C:42]1[CH:50]=[CH:49][C:45]([C:46]([OH:48])=[O:47])=[CH:44][CH:43]=1)[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40].Cl>N1C=CC=CC=1>[CH2:33]([O:41][C:42]1[CH:43]=[CH:44][C:45]([C:46]([OH:48])=[O:47])=[CH:49][CH:50]=1)[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40].[OH:13][C:10]1[CH:9]=[CH:8][C:7]([C:6]2[CH:1]=[CH:2][CH:3]=[CH:4][CH:5]=2)=[CH:12][CH:11]=1
Reactant: Oc1ccc(-c2ccc(O)cc2)cc1
Agent: CCCCCCCCOc1ccc(C(=O)Cl)cc1
Agent: CCCCCCCCOc1ccc(C(=O)O)cc1
Agent: Cl
Solvent: c1ccncc1
Product: Oc1ccc(-c2ccccc2)cc1
Temperature: 25 °C

Procedure:
11.2 g (0.06 mol) of p,p'-biphenol and 5.4 g (0.02 mol) of 4-octyloxybenzoyl chloride derived from 4-octyloxybenzoic acid were dissolved in 100 ml of dried pyridine, which were stirred at room temperature for a night. After the completion of the reaction, the reaction mixture was added with 6 normal hydrochloric acid to adjust pH to not more than 1 and then the precipitate was taken out by filtration. Thus obtained precipitate was recrystallized from ethanol to obtain 4.4 g (yield: 53%) of a white crystal.
Reaction SMILES: Br[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[NH:19]1[CH2:24][CH2:23][CH:22]([C:25]([NH2:27])=[O:26])[CH2:21][CH2:20]1>O1CCCC1.O>[C:25]([CH:22]1[CH2:23][CH2:24][N:19]([CH2:2][CH2:3][O:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:20][CH2:21]1)(=[O:26])[NH2:27]
Reactant: BrCCOc1ccccc1CCc1ccccc1
Reactant: NC(=O)C1CCNCC1
Solvent: C1CCOC1
Solvent: O
Product: NC(=O)C1CCN(CCOc2ccccc2CCc2ccccc2)CC1
Yield: 82.3 %

Procedure:
A solution of 2 g of 2-(2-bromoethoxy)bibenzyl and 1.7 g of 4-piperidinecarboxamide in 20 ml of tetrahydrofuran and 10 ml of water was stirred at 70° C. for 10 hours. The reaction mixture was concentrated and to the residue was added 1 N NaOH aqueous solution. The resultant crystals were filtered, washed well with water and then recrystallized from ethanol to give 1.9 g (82% yield) of 2-[2-(4-carbamoylpiperidino)ethoxy]bibenzyl, m. p. 60°-63° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH3:11])[CH:8]=[C:7]2[CH2:12][NH:13][CH3:14].[O:15]=[C:16]1[NH:25][C:24]2[N:23]=[CH:22][C:21](/[CH:26]=[CH:27]/[C:28]([OH:30])=O)=[CH:20][C:19]=2[CH2:18][CH2:17]1.C1C=CC2N(O)N=NC=2C=1.O.C(Cl)CCl>CN(C=O)C.CCN(CC)CC>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH3:11])[CH:8]=[C:7]2[CH2:12][N:13]([CH3:14])[C:28](=[O:30])/[CH:27]=[CH:26]/[C:21]1[CH:22]=[N:23][C:24]2[NH:25][C:16](=[O:15])[CH2:17][CH2:18][C:19]=2[CH:20]=1
Reactant: CNCc1cn(C)c2c(Cl)cccc12
Reactant: O=C(O)/C=C/c1cnc2c(c1)CCC(=O)N2
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CN(Cc1cn(C)c2c(Cl)cccc12)C(=O)/C=C/c1cnc2c(c1)CCC(=O)N2
Temperature: 25 °C
Reaction time: 20 h
Yield: 46.5 %

Procedure:
A solution of 7-chloro-1-methyl-3-(methylaminomethyl)-1H-indole (104.3 mg, 0.5 mmole) and (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-acrylic acid (109.1 mg, 0.5 mmole) in dry DMF (8 mL) was treated with dry Et3N (0.2 mL), HOBt H2O (76.5 mg, 0.5 mmole) and EDC (96 mg, 0.5 mmole). The solution was stirred at RT under argon for 20 h, then was concentrated. The oily residue was dissolved in MeOH and the solution was cooled. The precipitated solid was collected, washed with cold MeOH, and dried to give the title compound (95 mg, 47%): MS (ES) m/e 409.2 (M+H)+. Anal. Calcd for C22H21ClN4O2.0.25H2O: C, 63.92; H, 5.24; N, 13.55. Found: C, 63.56; H, 5.14; N, 13.73.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[C:10](=[O:11])[C:9]2=[CH:12][CH:13]=[CH:14][CH:15]=[C:8]2[C:7]1=[O:16])=[O:5])[CH3:2].[CH2:17]([OH:24])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][OH:23]>>[OH:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][O:24][C:7]([C:8]1[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=1[C:10]([NH:6][C:4](=[O:5])[O:3][CH2:1][CH3:2])=[O:11])=[O:16]
Reactant: CCOC(=O)N1C(=O)c2ccccc2C1=O
Reactant: OCCCCCCO
Product: CCOC(=O)NC(=O)c1ccccc1C(=O)OCCCCCCO

Procedure:
According to the same manner as described in Example 1 except for reacting N-ethoxycarbonylphthalimide with 1,6-hexanediol under conditions shown in Table 19, ethyl N-{2-(6-hydroxyhexyloxycarbonyl)benzoyl)carbamate was obtained. Characteristics and identified structure of the resulting compound are shown in Table 7.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:40]=[CH:39][CH:38]=[CH:37][C:4]=1[CH2:5][N:6]1[C:11](=[O:12])[C:10]2[N:13]([CH:20]3[CH2:25][CH2:24][N:23](C(OCC4C=CC=CC=4)=O)[CH2:22][CH2:21]3)[N:14]=[C:15]([C:16]([F:19])([F:18])[F:17])[C:9]=2[C:8]([CH3:36])=[N:7]1>CCO.[Pd]>[CH3:1][O:2][C:3]1[CH:40]=[CH:39][CH:38]=[CH:37][C:4]=1[CH2:5][N:6]1[C:11](=[O:12])[C:10]2[N:13]([CH:20]3[CH2:21][CH2:22][NH:23][CH2:24][CH2:25]3)[N:14]=[C:15]([C:16]([F:17])([F:18])[F:19])[C:9]=2[C:8]([CH3:36])=[N:7]1
Reactant: COc1ccccc1Cn1nc(C)c2c(C(F)(F)F)nn(C3CCN(C(=O)OCc4ccccc4)CC3)c2c1=O
Agent: [Pd]
Solvent: CCO
Product: COc1ccccc1Cn1nc(C)c2c(C(F)(F)F)nn(C3CCNCC3)c2c1=O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a stirred solution of 113 (81 mg, 0.146 mmol) in EtOH (1.5 mL) was added Pd/C (10% Degussa type, 15.5 mg, 0.015 mmol). The resulting suspension was allowed to stir for 30 min at room temperature under latm of H2 gas. The catalyst was filtrate over Celite and the solvent was evaporated to give crude 114. LRMS (ESI): calc. 421.4; found 422.3 (MH)+.
Reaction SMILES: [CH2:1]([C@@H:8]1[NH:13][CH2:12][CH2:11][N:10]([C:14]2[CH:22]=[C:21]3[C:17]([C:18]([CH3:28])=[N:19][N:20]3[CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.C[Si]([N:42]=[C:43]=[O:44])(C)C>C(Cl)Cl>[CH2:1]([C@H:8]1[CH2:9][N:10]([C:14]2[CH:22]=[C:21]3[C:17]([C:18]([CH3:28])=[N:19][N:20]3[CH:23]3[CH2:24][CH2:25][CH2:26][CH2:27]3)=[CH:16][CH:15]=2)[CH2:11][CH2:12][N:13]1[C:43]([NH2:42])=[O:44])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1nn(C2CCCC2)c2cc(N3CCN[C@@H](Cc4ccccc4)C3)ccc12
Reactant: C[Si](C)(C)N=C=O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1nn(C2CCCC2)c2cc(N3CCN(C(N)=O)[C@@H](Cc4ccccc4)C3)ccc12
Reaction time: 16 h
Yield: 35.9 %

Procedure:
A solution of 6-((S)-3-benzyl-piperazin-1-yl)-1-cyclopentyl-3-methyl-1H-indazole (44 mg, 0.12 mmol) in CH2Cl2 (1 mL) was treated with diisopropylethylamine (21 μL, 0.12 mmol) followed by trimethylsilyl isocyanate (31 μL, 0.24 mmol). The reaction mixture was stirred for 16 h after which time an additional equivalent of TMS-isocyanate was added and the reaction mixture was stirred an additional 16 h. The reaction mixture was evaporated and purified by reverse phase HPLC. Product was obtained as a colorless solid (18 mg, 36%). LC/MS (Method B) 3.64 min, [M+1]+ 418.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=1.N1CCC[C@H]1C(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[CH:33]=[C:34]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[F:42])[CH3:35]>CN(C=O)C.[Cu]I>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](/[CH:33]=[C:34](/[C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=3[F:42])\[CH3:35])[C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=1
Reactant: CC(=CBr)c1ccccc1F
Reactant: CN1CCc2[nH]c3ccc(Cl)cc3c2C1
Agent: [Cu]I
Agent: O=C(O)[C@@H]1CCCN1
Agent: O=P([O-])([O-])[O-]
Solvent: CN(C)C=O
Product: C/C(=C\n1c2c(c3cc(Cl)ccc31)CN(C)CC2)c1ccccc1F
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
8-Chloro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (200 mg, 1 mmol) was dissolved in DMF (5 mL). Copper (I) iodide (19 mg, 0.1 mmol), L-proline (23 mg, 0.2 mmol) and potassium phosphate (424 mg, 2 mmol) were added and the reaction mixture was stirred for 10 min. at RT. 1-(1-Bromoprop-1-en-2-yl)-2-fluorobenzene (260 mg, 1.2 mmol) was added dropwise and the reaction mixture was purged with nitrogen. The reaction mixture was heated overnight at 85° C. (prolonged heating in some cases was required). DMF was evaporated under reduced pressure, the residue was diluted with water and the solid was filtered. The solid material was purified by silica gel chromatography (100-200 mesh) eluting with 0-1% MeOH-DCM. The product was further purified by HPLC. Yield: 5 mg. 1H NMR (CDCl3, TFA salt) δ (ppm): 7.40 (m, 3H), 7.20 (m, 4H), 6.70 (d, 1H), 4.80 (m, 1H), 4.20 (m, 1H), 3.80 (m, 1H), 3.40-3.20 (m, 3H), 3.05 (s, 3H), 1.85 (s, 3H).
Reaction SMILES: B(Br)(Br)Br.C[O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]#[C:14][C:15]2[S:19][C:18]([C:20]#[N:21])=[CH:17][CH:16]=2)=[CH:9][CH:8]=1.O>ClCCl>[OH:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]#[C:14][C:15]2[S:19][C:18]([C:20]#[N:21])=[CH:17][CH:16]=2)=[CH:11][CH:12]=1
Reactant: COc1ccc(C#Cc2ccc(C#N)s2)cc1
Agent: BrB(Br)Br
Solvent: ClCCl
Solvent: O
Product: N#Cc1ccc(C#Cc2ccc(O)cc2)s1
Reaction time: 8 h
Yield: 63.7 %

Procedure:
A 1M solution of boron tribromide in dichloromethane (75 cm3) is added dropwise to a solution of 1-(4-methoxyphenyl)-2-(2-cyanothiophen-5-yl)acetylene (3.0 g) and dichloromethane (100 cm3) at 0° C. under an atmosphere of nitrogen. The reaction solution is stirred overnight and water (100 cm3) added. The organic layer is separated off and the aqueous layer extracted with dichloromethane (2×100 cm3). The combined organic layers are washed with brine (2×100 cm3) and then dried (MgSO4), filtered and evaporated down. The residue is purified by column chromatography on silica gel using a 9:1 hexane/ethyi acetate mixture as eluent and recrystallisation from ethanol to yield 1.8 g of g 1-(4-hydroxyphenyl)-2-(2-cyanothiophen-5-yl)acetylene.
Reaction SMILES: Cl[C:2]1[C:11]([CH:12]=[O:13])=[CH:10][C:9]2[CH:8]=[C:7]3[O:14][CH2:15][O:16][C:6]3=[CH:5][C:4]=2[N:3]=1.[CH3:17][NH:18][CH3:19]>O1CCOCC1>[CH3:17][N:18]([CH3:19])[C:2]1[C:11]([CH:12]=[O:13])=[CH:10][C:9]2[CH:8]=[C:7]3[O:14][CH2:15][O:16][C:6]3=[CH:5][C:4]=2[N:3]=1
Reactant: CNC
Reactant: O=Cc1cc2cc3c(cc2nc1Cl)OCO3
Solvent: C1COCCO1
Product: CN(C)c1nc2cc3c(cc2cc1C=O)OCO3
Temperature: 160 °C
Reaction time: 0.75 h

Procedure:
To a stirred solution of 6-chloro-[1,3]dioxolo[4,5-g]quinoline-7-carbaldehyde (1.0 g, 4.07 mmol) in dioxane (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added dimethylamine (40% in water, 5.1 mL, 40.7 mmol) and the reaction mixture was stirred for 45 min at 160° C. under microwave irradiation. After cooling to RT, the volatiles were removed at 40° C. under vacuum and the resulting yellow oil was taken back in water (30 mL). The precipitate formed was filtered through a fritted glass filter (porosity 3) to give after evaporation 6-(dimethylamino)-[1,3]dioxolo[4,5-g]quinoline-7-carbaldehyde RBO 35166 (960 mg, 97%).
Reaction SMILES: C([N:8](CC1C=CC=CC=1)[C@@H:9]1[CH2:22][CH2:21][C@:20]2([O:23][CH3:24])[C@:11]34[CH2:27][CH2:26][N:25]([CH3:28])[C@@H:19]2[CH2:18][C:17]2[CH:16]=[CH:15][C:14]([OH:29])=[C:13]([O:30][C@@H:10]13)[C:12]4=2)C1C=CC=CC=1.C1CCCCC=1>[Pd].CO>[NH2:8][C@@H:9]1[CH2:22][CH2:21][C@:20]2([O:23][CH3:24])[C@:11]34[CH2:27][CH2:26][N:25]([CH3:28])[C@@H:19]2[CH2:18][C:17]2[CH:16]=[CH:15][C:14]([OH:29])=[C:13]([O:30][C@@H:10]13)[C:12]4=2
Reactant: CO[C@@]12CC[C@@H](N(Cc3ccccc3)Cc3ccccc3)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
Agent: [Pd]
Solvent: CO
Solvent: C1=CCCCC1
Product: CO[C@@]12CC[C@@H](N)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5

Procedure:
A mixture of Compound 14 (1.02 g, 2.05 mmol), 10% Pd/C catalyst (0.52 g), cyclohexene (30 ml) and absolute MeOH (30 ml) were reflux heated for 16 hours under N2. Then the catalyst was filtered off and the filtrate evaporated. The residue (0.66 g of white foam resin) was crystallised out of i-PrOH/Et2O 1:1 (2 ml). Yield: 0.33 g (42%) of beige crystals: Fp>235-239° C.; IR (KBr): 3348 (OH) cm−1; 1H-NMR (CDCl3): 6.62 (d, J=8.0, 1 arom. H); 6.54 (d, J=8.0, 1 arom. H); 4.26 (d, J=7.0, H—C(5)); 3.22 (s, CH3O—C(14)); 2.36 (s, CH3N); Cl-MS: m/z 317 (M++1).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:16]=[C:15]3[C:11]([CH2:12][N:13]([C@@H:18]([CH:23]([CH3:25])C)[C:19]([O:21][CH3:22])=[O:20])[C:14]3=[O:17])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[N+](C1C=CC(C2C=C3C(CN(C4(C(OC)=O)CC4)C3=O)=CC=2)=CC=1)([O-])=O>>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:16]=[C:15]3[C:11]([CH2:12][N:13]([C:18]4([C:19]([O:21][CH3:22])=[O:20])[CH2:25][CH2:23]4)[C:14]3=[O:17])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1
Reactant: COC(=O)[C@H](C(C)C)N1Cc2ccc(-c3ccc(N)cc3)cc2C1=O
Agent: COC(=O)C1(N2Cc3ccc(-c4ccc([N+](=O)[O-])cc4)cc3C2=O)CC1
Product: COC(=O)C1(N2Cc3ccc(-c4ccc(N)cc4)cc3C2=O)CC1
Yield: 61 %

Procedure:
The compound of example 584 was prepared analogous to the compound of example 6 by reduction of the compound of example 583.