Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[C:8]([Cl:9])=[N:7][C:5](Cl)=[N:4][C:2]=1[Cl:3].[CH2:10]([CH:12]([CH2:15][CH2:16][CH2:17][CH3:18])[CH2:13][NH2:14])[CH3:11]>>[Cl:9][C:8]1[NH:7][C:5](=[N:14][CH2:13][CH:12]([CH2:10][CH3:11])[CH2:15][CH2:16][CH2:17][CH3:18])[N:4]=[C:2]([Cl:3])[N:1]=1
Reactant: CCCCC(CC)CN
Reactant: Clc1nc(Cl)nc(Cl)n1
Product: CCCCC(CC)CN=c1nc(Cl)nc(Cl)[nH]1

Procedure:
Similarly to the process reported in example 1, the cyanuryl chloride was reacted with 2-ethyl-1-hexylamine, to obtain the corresponding intermediate 2,4-bischloro-6-(2-ethylhexyl)imino-1,3,5-triazine. Similarly to the process reported in examples 2 and 3, the latter was reacted with two equivalents of p-aminobenzoic acid to give the corresponding diacid, which was then converted to the corresponding diacyl chloride by the action of thionyl chloride.
Reaction SMILES: [NH2:1][C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[C:11]#[N:12].[C:13](Cl)(=[O:15])[CH3:14]>N1C=CC=CC=1>[C:13]([NH:1][C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[C:11]#[N:12])(=[O:15])[CH3:14]
Reactant: CC(=O)Cl
Reactant: N#Cc1oc2ccccc2c1N
Solvent: c1ccncc1
Product: CC(=O)Nc1c(C#N)oc2ccccc12
Temperature: 0 °C
Reaction time: 2 h
Yield: 58.3 %

Procedure:
A solution of 3.86 g (0.024 mole) of 3-amino-2-benzofurancarbonitrile in 50 ml of pyridine is cooled in ice and treated over 15 minutes with 2.0 ml (2.21 g; 0.028 mole) of acetyl chloride. The mixture is stirred in ice an additional two hours and added to 250 g of ice/water. The precipitated crude product is filtered, washed with water, and recrystallized from aqueous methanol to yield 2.8 g (57% yield) of 3-(acetylamino)-2-benzofurancarbonitrile. A sample recrystallized a second time as above is analytically pure, mp 187°-189° C.
Reaction SMILES: II.C[Si](C)(C)[Si](C)(C)C.[NH:11]1[C:19]2[C:14](=[CH:15][C:16]([NH:20][CH:21]3[CH2:27][CH:26]4[N:28](C(OCC)=O)[CH:23]([CH2:24][CH2:25]4)[CH2:22]3)=[CH:17][CH:18]=2)[CH:13]=[N:12]1.CO>ClCCCl>[CH:23]12[NH:28][CH:26]([CH2:25][CH2:24]1)[CH2:27][CH:21]([NH:20][C:16]1[CH:15]=[C:14]3[C:19](=[CH:18][CH:17]=1)[NH:11][N:12]=[CH:13]3)[CH2:22]2
Reactant: CCOC(=O)N1C2CCC1CC(Nc1ccc3[nH]ncc3c1)C2
Agent: C[Si](C)(C)[Si](C)(C)C
Agent: II
Solvent: CO
Solvent: ClCCCl
Product: c1cc2[nH]ncc2cc1NC1CC2CCC(C1)N2
Temperature: 25 °C
Yield: 57.9 %

Procedure:
A solution of iodine (0.488 g, 1.92 mmol) in hexamethyldisilane (0.560 g, 3.83 mmol) was heated at 110° C. and stirred until the purple solution became colorless. The solution was cooled to room temperature, followed by adding thereto a solution of the ethyl 3-(1H-indazol-5-ylamino)-8-azabicyclo[3.2.1]octane-8-carboxylate (0.200 g, 0.637 mmol) obtained in Example 14 in 1,2-dichloroethane (6 ml), and the resulting mixture was heated at 50° C. and stirred for 7 hours. The mixture was cooled to room temperature and methanol was added thereto to quench the mixture. Then, the solvent was distilled off under reduced pressure and a 1N-aqueous sodium hydroxide solution was added to the residue. The solvent was distilled off under reduced pressure and the residue was dried up and then purified by a silica gel chromatography (eluent: chloroform/methanol/30%-aqueous ammonia=100/10/1) to obtain N-(8-azabicyclo[3.2.1]oct-3-yl)-1H-indazol-5-amine (0.0893 g, 58%).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=[O:10].[Br:12][C:13]1[CH:19]=[CH:18][CH:17]=[C:16]([Br:20])[C:14]=1[NH2:15]>>[Br:12][C:13]1[CH:19]=[CH:18][CH:17]=[C:16]([Br:20])[C:14]=1[NH:15][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=[O:10]
Reactant: Nc1c(Br)cccc1Br
Reactant: O=C(O)Cc1ccccc1Br
Product: O=C(O)Cc1ccccc1Nc1c(Br)cccc1Br

Procedure:
In the manner described in example 3, 2-bromophenylacetic acid is condensed with 2,6-dibromoaniline to yield 2-[(2,6-dibromophenyl)amino]phenylacetic acid.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[N:7][CH:6]=[CH:5][N:4]=1.Cl[C:10]1C(CCl)=CC=C(Cl)[N:11]=1>>[CH3:10][NH:11][CH2:2][C:3]1[CH:8]=[N:7][CH:6]=[CH:5][N:4]=1
Reactant: ClCc1ccc(Cl)nc1Cl
Reactant: ClCc1cnccn1
Product: CNCc1cnccn1

Procedure:
The reaction according to Reference Example 11 was carried out using 2-chloromethylpyrazine in lieu of 2,6-dichloro-3-pyridylmethyl chloride to give the title compound as oil.
Reaction SMILES: [N:1]1([C:7]([N:9]2[CH2:14][CH:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=3)[CH2:12][CH:11]([C:25](=[S:27])[NH2:26])[CH2:10]2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:29][C:30]([C:32]1[CH:33]=[N:34][C:35]([Cl:38])=[CH:36][CH:37]=1)=O>>[Cl:38][C:35]1[N:34]=[CH:33][C:32]([C:30]2[N:26]=[C:25]([CH:11]3[CH2:12][CH:13]([C:15]4[CH:20]=[CH:19][C:18]([C:21]([F:22])([F:23])[F:24])=[CH:17][CH:16]=4)[CH2:14][N:9]([C:7]([N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)=[O:8])[CH2:10]3)[S:27][CH:29]=2)=[CH:37][CH:36]=1
Reactant: NC(=S)C1CC(c2ccc(C(F)(F)F)cc2)CN(C(=O)N2CCOCC2)C1
Reactant: O=C(CBr)c1ccc(Cl)nc1
Product: O=C(N1CCOCC1)N1CC(c2ccc(C(F)(F)F)cc2)CC(c2nc(-c3ccc(Cl)nc3)cs2)C1

Procedure:
100 mg (0.224 mmol) of 1-(morpholin-4-ylcarbonyl)-5-[4-(trifluoromethyl)phenyl]piperidine-3-carbothioamide (Example 53A) and 85 mg (0.269 mmol) of 2-bromo-1-(6-chloropyridin-3-yl)ethanone were reacted according to the General Method 3. Yield: 17 mg (14% of theory)
Reaction SMILES: [OH-].[K+].[C:3]1([SH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[N+:18]([O-:20])=[O:19]>CN(C)C=O>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([S:9][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)=[C:12]([N+:18]([O-:20])=[O:19])[CH:13]=1
Reactant: O=[N+]([O-])c1cc(Cl)ccc1Cl
Reactant: Sc1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1cc(Cl)ccc1Sc1ccccc1
Reaction time: 3 h
Yield: 57 %

Procedure:
Potassium hydroxide (6.15 g; 87%) was added to a stirred solution of thiophenol (10.0 g) in N,N-dimethylformamide (170 mL) at room temperature. When most of the potassium hydroxide appeared to have dissolved, 2,5-dichloronitrobenzene (17.4 g) was added, and the initially dark solution turned a bright yellow with some precipitate. The reaction was placed in an oil bath at 70° C. for three hours, and then evaporated in vacuo. The residue was partitioned between chloroform and 1 N NaOH and the layers were separated. The aqueous layer was extracted once more with chloroform. The chloroform solutions were combined, washed with 1 N NaOH, H2O, 1 N HCl, H2O and brine, dried over MgSO4, and evaporated in vacuo. The resulting oil was treated with cyclohexane, and the product crystallized. The crystalline product was collected by filtration, washed with hexane, and dried in vacuo at 56° C. to yield 13.73 g (57%) of yellow crystals. mp: 84°-86° C.
Reaction SMILES: [NH2:1][C:2]1[N:6]=[C:5]([SH:7])[NH:4][N:3]=1.[C:8]([CH2:16][C:17](=O)[CH3:18])(=O)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(Cl)Cl.O>C(O)(=O)C>[CH3:18][C:17]1[CH:16]=[C:8]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:3]2[N:4]=[C:5]([SH:7])[N:6]=[C:2]2[N:1]=1
Reactant: CC(=O)CC(=O)c1ccccc1
Reactant: Nc1n[nH]c(S)n1
Solvent: ClCCl
Solvent: CC(=O)O
Solvent: O
Product: Cc1cc(-c2ccccc2)n2nc(S)nc2n1

Procedure:
A mixture of 10.0 9 (86 mmol) 3-amino-5-mercapto-1,2,4-triazole and 14.0 g (86.5 mmol) of benzoylacetone in 100 ml of glacial acetic acid was heated at reflux 4 hours. Methylene chloride (500 ml) and excess water were added. The organic layer was separated and washed with water, brine, dried over magnesium sulfate and evaporated in vacuo to give a residue to which n-butyl chloride was added. Filtering gave 4.9 g of crude 5-methyl-7-phenyl-1,2,4-triazolo[1,5-a]pyrimidin-2-thiol which was used directly in the next step.
Reaction SMILES: [C:1]([NH:4][C@@H:5]1[C@@H:11]([OH:12])[C@H:10]([OH:13])[C@@H:9]([CH2:14][OH:15])[O:8][CH:6]1O)(=[O:3])[CH3:2].[CH2:16]([NH2:34])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33].[CH2:35]([OH:37])[CH3:36]>>[C:1]([NH:4][C@@H:5]1[C@@H:11]([OH:12])[C@H:10]([OH:13])[C@@H:9]([CH2:14][OH:15])[O:8][CH:6]1[N:34]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[C:35](=[O:37])[CH2:36][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]/[CH:22]=[CH:23]\[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])(=[O:3])[CH3:2]
Reactant: CCCCCCCCCCCCCCCCCCN
Reactant: CCO
Reactant: CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O
Product: CCCCCCCC/C=C\CCCCCCCC(=O)N(CCCCCCCCCCCCCCCCCC)C1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1NC(C)=O

Procedure:
15 g of N-acetyl-D-glucosamine and 18.8 g of octadecylamine were heated at 80° C. in 50 ml of ethanol for 3 hours, with stirring. The undissolved material was then filtered off hot, the filtrate was cooled and the product which had precipitated was filtered off with suction and washed with ethanol and ether.2.2 g of the 2-acetamido-2-deoxy-N-octadecyl-glucopyranosylamine thus obtained were stirred in 17 ml of THF with 2 g of sodium carbonate. 1.45 g of oleoy) chloride in 5 ml of THF were then added dropwise.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11]2[C:12](=[O:26])O[C:14](=[O:25])[C:15]=2[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([N+:22]([O-:24])=[O:23])[CH:17]=2)=[CH:3]1.[NH3:27].O>CN(C=O)C>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11]2[C:12](=[O:26])[NH:27][C:14](=[O:25])[C:15]=2[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([N+:22]([O-:24])=[O:23])[CH:17]=2)=[CH:3]1
Reactant: Cn1cc(C2=C(c3cccc([N+](=O)[O-])c3)C(=O)OC2=O)c2ccccc21
Reactant: N
Solvent: CN(C)C=O
Solvent: O
Product: Cn1cc(C2=C(c3cccc([N+](=O)[O-])c3)C(=O)NC2=O)c2ccccc21
Reaction time: 6 h
Yield: 75 %

Procedure:
A solution of 3-(1-methylindol-3-yl)-4-(3-nitrophenyl)furan-2,5-dione (9 g, 26 mmol) in DMF (20 mL) was heated to about 140° C. Aqueous ammonia (20 mL) was added in portions and the heating was continued for 6 h. Water (20 mL) was added and the reaction mixture was allowed to stand at room temperature overnight. The orange colored solid was filtered off, washed with water and dried under vacuum to afford 3-(1-methylindol-3-yl)-4-(3-nitrophenyl)-1H-pyrrole-2,5-dione (6.7 g, 75%).
Reaction SMILES: CN(C)/[N:3]=[CH:4]/[C:5]([CH3:7])=[CH2:6].C(OC(=O)C)(=O)C.Br[C:17]1[C:18](=[O:25])[CH:19]=[C:20]([CH3:24])[C:21](=[O:23])[CH:22]=1>CC#N>[CH3:7][C:5]1[CH:4]=[N:3][C:22]2[C:21](=[O:23])[C:20]([CH3:24])=[CH:19][C:18](=[O:25])[C:17]=2[CH:6]=1
Reactant: C=C(C)/C=N/N(C)C
Reactant: CC1=CC(=O)C(Br)=CC1=O
Solvent: CC#N
Solvent: CC(=O)OC(C)=O
Product: CC1=CC(=O)c2cc(C)cnc2C1=O
Temperature: 25 °C

Procedure:
(E)-1,1-dimethyl-2-(2-methylallylidene)hydrazine (2.18 g, 19.50 mmol, 1.3 equiv.) and acetic anhydride (19.15 mL) were added in 250 mL of MeCN and stirred at room temperature. 2-bromo-5-methylcyclohexa-2,5-diene-1,4-dione (3 g, 14.9 mmol, 1 equiv.) in 125 mL of MeCN was then added dropwise (slowly during 60 min). The reaction mixture was stirred at room temperature during 120 minutes.
Reaction SMILES: [C:1]([NH:8][C@H:9]([C:13]([OH:15])=[O:14])[CH:10]([CH3:12])[CH3:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C1(N=C=NC2CCCCC2)CCCCC1.O[CH2:32][C@H:33]([CH2:46][CH2:47][O:48][C:49](=[O:67])[CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH3:66])[CH2:34][N:35]1[CH:43]=[N:42][C:41]2[C:40](=[O:44])[NH:39][C:38]([NH2:45])=[N:37][C:36]1=2.CN(C)C=O>ClCCl.CN(C)C1C=CN=CC=1>[C:1]([NH:8][C@H:9]([C:13]([O:15][CH2:32][C@H:33]([CH2:46][CH2:47][O:48][C:49](=[O:67])[CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH3:66])[CH2:34][N:35]1[CH:43]=[N:42][C:41]2[C:40](=[O:44])[NH:39][C:38]([NH2:45])=[N:37][C:36]1=2)=[O:14])[CH:10]([CH3:11])[CH3:12])([O:3][C:4]([CH3:5])([CH3:7])[CH3:6])=[O:2]
Reactant: CCCCCCCCCCCCCCCCCC(=O)OCC[C@@H](CO)Cn1cnc2c(=O)[nH]c(N)nc21
Reactant: CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CCCCCCCCCCCCCCCCCC(=O)OCC[C@@H](COC(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)C)Cn1cnc2c(=O)[nH]c(N)nc21
Temperature: 25 °C
Yield: 39.3 %

Procedure:
A mixture of N-Boc-L-valine (528 mg; 2.1 mmol) and N,N′-dicyclohexyl carbodiimide (250 mg; 1.21 mmol) in dichloromethane (20 ml) was stirred over night at room temperature, dicyclohexylurea filtered off and extracted with a small volume of dichloromethane, and the filtrate evaporated in vacuo to a small volume. (R)-9-[2-Hydroxymethyl-4-(stearoyloxy)butyl]guanine (340 mg; 0.654 mmol), 4-dimethylaminopyridine (25 mg; 0.205 mmol), and dry N,N-dimethylformamide (15 ml) were added and the mixture was stirred for 4 h at 50° C. under N2. The solvent was evaporated in vacuo to a small volume. Column chromatography on silica gel, then on aluminum oxide (ethyl acetate:methanol:water 15:2:1 as eluent) gave 185 mg (39%) pure title compound as a white solid.
Reaction SMILES: [CH2:1]=O.[N+:3]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]=[C:9]2[CH2:15][CH2:16][NH:17][CH3:18])([O-:5])=[O:4].O.[OH-].[Na+]>C(O)(=O)C.CCOC(C)=O>[CH3:18][N:17]1[CH2:16][CH2:15][C:9]2[C:8]3[C:12](=[CH:13][CH:14]=[C:6]([N+:3]([O-:5])=[O:4])[CH:7]=3)[NH:11][C:10]=2[CH2:1]1
Reactant: C=O
Reactant: CNCCc1c[nH]c2ccc([N+](=O)[O-])cc12
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: CN1CCc2c([nH]c3ccc([N+](=O)[O-])cc23)C1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
Under N2, formaldehyde (0.56 ml of a 36.5% aqueous solution, 7.3 mmol) was added to a solution of 5-nitro-3-(2-methylaminoethyl)-1H-indole (1.6 g, 7.3 mmol) in glacial acetic acid (10 mL). After 20 h of stirring at room temperature, the mixture was refluxed for 2 h and taken to dryness in vacuo. The residue was treated with H2O (150 mL) and EtOAc (150 mL) and then basified by the addition of 2M NaOH. The organic phase was separated and the aqueous layer was reextracted with three portions of EtOAc. The combined organic solution was extracted with 10% aqueous H2SO4 (3×160 mL). The acidic aqueous phase was cooled in an ice bath, basified with concentrated aqueous NaOH and extracted with tert-butyl methyl ether (4×175 mL). The dried (Na2SO4) extract was evaporated to dryness to afford 1.40 g of 2-methyl-6-nitro-2,3,4,9-tetrahydro-1H-β-carboline that were used directly in the next step.
Reaction SMILES: [SH:1][C:2]1[NH:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[OH-].[K+].[C:13]([C:16]1[CH:26]=[CH:25][C:19]([O:20][CH2:21][CH2:22][CH2:23]Br)=[C:18]([CH2:27][CH2:28][CH3:29])[C:17]=1[OH:30])(=[O:15])[CH3:14]>C(O)C.ClCCl.O>[C:13]([C:16]1[CH:26]=[CH:25][C:19]([O:20][CH2:21][CH2:22][CH2:23][S:1][C:2]2[NH:3][C:4]3[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=3[N:6]=2)=[C:18]([CH2:27][CH2:28][CH3:29])[C:17]=1[OH:30])(=[O:15])[CH3:14]
Reactant: CCCc1c(OCCCBr)ccc(C(C)=O)c1O
Reactant: Sc1nc2ccccc2[nH]1
Agent: [K+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CCO
Solvent: O
Product: CCCc1c(OCCCSc2nc3ccccc3[nH]2)ccc(C(C)=O)c1O
Yield: 81.4 %

Procedure:
To a suspension of 1.2 g of 2-mercaptobenzimidazole in 30 ml of ethanol was added 580 mg of potassium hydroxide under stirring and stirred at room termperature for 10 minutes. To this solution was added 2.8 g of 3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylbromide at one time, and stirred at room temperature for 4 hours. The solvent was distilled off under reduced pressure and resulting residue was diluted with dichloromethane-water, then extracted with dichloromethane three times. The organic layer was combined, then washed with water saturated with sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, the resulting residue was recrystallized from dichloromethane-n-hexane to give 2.5 g (yield 81%) of the aimed compound as colorless powder. mp 149°-150° C.
Reaction SMILES: N1C=CN=C1.[Si:6](Cl)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].[CH2:14]([O:21][C:22]([N:24]1[CH2:29][CH2:28][CH2:27][CH:26]([CH2:30][OH:31])[CH2:25]1)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.O>CN(C)C=O>[CH2:14]([O:21][C:22]([N:24]1[CH2:29][CH2:28][CH2:27][CH:26]([CH2:30][O:31][Si:6]([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7])[CH2:25]1)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: O=C(OCc1ccccc1)N1CCCC(CO)C1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)[Si](C)(C)OCC1CCCN(C(=O)OCc2ccccc2)C1
Temperature: 25 °C
Reaction time: 6 h
Yield: 98.9 %

Procedure:
Imidazole (3.00 g, 44.0 mmol) and tert-butyldimethylsilyl chloride (6.63 g, 44.0 mmol) were added to 1-(benzyloxycarbonyl)piperidin-3-yl methanol (9.15 g, 36.7 mmol) in N,N-dimethylformamide (40 mL). The solution was stirred at room temperature for 6 hours. Subsequently, water was added and the mixture was extracted with ethyl acetate. The extract washed with brine and was dried over magnesium sulfate, followed by evaporation of the solvent. Purification of the residue by silica gel column chromatography (hexane:ethyl acetate=20:1->5:1) gave 13.2 g (99%) of the desired compound as a colorless oil.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].CC1(C)C(C)(C)OB([C:22]2[CH:30]=[C:29]3[C:25]([C:26]([NH:39][C:40](=[O:44])[CH2:41][CH2:42][CH3:43])=[N:27][N:28]3[CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])=[CH:24][CH:23]=2)O1>O1CCOCC1.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.O.C(OCC)(=O)C>[N:5]1[CH:6]=[CH:7][C:2]([C:22]2[CH:30]=[C:29]3[C:25]([C:26]([NH:39][C:40](=[O:44])[CH2:41][CH2:42][CH3:43])=[N:27][N:28]3[CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:36])[CH3:37])=[CH:24][CH:23]=2)=[CH:3][CH:4]=1
Reactant: Ic1ccncc1
Reactant: CCCC(=O)Nc1nn(COCC[Si](C)(C)C)c2cc(B3OC(C)(C)C(C)(C)O3)ccc12
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: O
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: CCCC(=O)Nc1nn(COCC[Si](C)(C)C)c2cc(-c3ccncc3)ccc12
Yield: 97.9 %

Procedure:
246 mg of 4-iodopyridine, 10 cm3 of water, 201 mg of sodium carbonate and 69 mg of tetrakis(triphenylphosphine)palladium are added to 320 mg of N-[6-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously, in 20 cm3 of dioxane. The medium is refluxed for 20 hours, the mixture is then allowed to return to room temperature and 50 cm3 of ethyl acetate and 50 cm3 of water are added. The combined organic phases are washed with 50 cm3 of distilled water and then with 50 cm3 of saturated aqueous sodium chloride solution, and then dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45° C.). The residue is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with a cyclohexane/ethyl acetate mixture (70/30 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). 280 mg of N-[6-(4-pyridyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide are obtained in the form of a yellow oil.
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][C:11]3[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][CH:12]=3)=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.Cl.[NH2:20][NH:21][C:22]([NH2:24])=[O:23].C([O-])(=O)C.[Na+]>C(O)C.O>[CH2:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][C:11]3[CH:18]=[CH:17][C:14]([CH:15]=[N:20][NH:21][C:22]([NH2:24])=[O:23])=[CH:13][CH:12]=3)=[CH:7][CH:8]=2)[CH2:3][CH2:2]1
Reactant: O=Cc1ccc(Oc2ccc3c(c2)CCC3)cc1
Reactant: NNC(N)=O
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: NC(=O)NN=Cc1ccc(Oc2ccc3c(c2)CCC3)cc1
Reaction time: 1 h
Yield: 97.6 %

Procedure:
To a solution of 4-(5-indanoxy)benzaldehyde (6.2 g) in ethanol (100 mL) was added a solution of semicarbazide hydrochloride (3.2 g) and sodium acetate (2.3 g) in water (50 mL) at room temperature. The mixture was stirred for 1 h, and the resulting solid was collected by filtration, washed with water (3×100 mL) and dried in vacuo to yield the title compound as a pale yellow solid (7.5 g, 97%), mp: 218-220° C. 1H NMR (DMSO-d6): δ 10.19 (s, 1H), 7.80 (s, 1H), 7.70 (d, J=8.7, 2H), 7.24 (d, J=8.1, 1H), 6.94 (d, J=8.7, 2H), 6.92 (s, 1H), 6.82 (d, J=8.1, 1H), 6.45 (s, 2H), 2.84 (t, J=7.5, 4H), 2.05 (m, 2H).
Reaction SMILES: [NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.[C:14](Cl)(=[O:18])[CH:15]([CH3:17])[CH3:16].C(N(CC)CC)C>C(Cl)Cl>[C:14]([NH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1)(=[O:18])[CH:15]([CH3:17])[CH3:16]
Reactant: CC(C)(C)OC(=O)N1CC[C@H](N)C1
Reactant: CC(C)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)C(=O)N[C@H]1CCN(C(=O)OC(C)(C)C)C1
Reaction time: 2 h

Procedure:
tert-Butyl (3S)-3-aminopyrrolidine-1-carboxylate (0.09 mL, 0.5 mmol) was combined with isobutyryl chloride (0.067 mL, 0.64 mmol) and triethylamine (0.22 mL, 1.6 mmol) in methylene chloride (2 mL) at room temperature and stirred for 2 hours. The reaction was diluted with dichloromethane, washed with water, dried over MgSO4 and concentrated. The residue was purified on silica gel (eluting with 0 to 10% methanol in dichloromethane) to give tert-butyl (3S)-3-(isobutyrylamino)pyrrolidine-1-carboxylate, LCMS [M+Na] 279.2. The latter was treated with 4.57 M hydrogen chloride in 1,4-dioxane (1 mL, 4 mmol) at room temperature for 1 hour. The mixture was concentrated to give the crude product (35 mg, 30%), which was used directly in the next step. LCMS calculated for C8H17N2O (M+H)+: m/z=157.1; Found: 157.2.
Reaction SMILES: [CH2:1]([CH:4]([CH2:15][CH:16]=[CH2:17])[CH2:5][O:6][SiH2:7][C:8]1[CH:13]=[CH:12][C:11](I)=[CH:10][CH:9]=1)[CH:2]=[CH2:3].C1COCC1.CCN(CC)CC.[CH3:30][C:31]([OH:38])([CH2:34][CH:35]([CH3:37])[CH3:36])[C:32]#[CH:33]>CCOCC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH2:1]([CH:4]([CH2:15][CH:16]=[CH2:17])[CH2:5][O:6][SiH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:33]#[C:32][C:31]([CH3:30])([OH:38])[CH2:34][CH:35]([CH3:37])[CH3:36])=[CH:10][CH:9]=1)[CH:2]=[CH2:3]
Reactant: C=CCC(CC=C)CO[SiH2]c1ccc(I)cc1
Reactant: C#CC(C)(O)CC(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCN(CC)CC
Solvent: CCOCC
Solvent: C1CCOC1
Product: C=CCC(CC=C)CO[SiH2]c1ccc(C#CC(C)(O)CC(C)C)cc1
Yield: 88.3 %

Procedure:
Firstly, a mixture of 4-(diallylethoxysilyl)iodobenzene (147 mg, 0.41 mmol), PdCl2(PPh3)2 (11.5 mg, 0.016 mmol) and CuI (3.1 mg, 0.016 mmol) was added with dist. THF (2 mL), dist. Et3N (3 mL) and 3,5-dimethyl-1-hexyn-3-ol (79 μL, 0.54 mmol). The resultant mixture was stirred under a nitrogen atmosphere at 50° C. for 3 hours to obtain a reaction mixture. Then, the reaction mixture was diluted with ether, and an organic layer was washed with dist. H2O and sat. NaCl. After that, the organic layer was dried with MgSO4, and the dried organic layer was then filtered and concentrated to obtain a crude product. The obtained crude product was separated and purified by silica gel column chromatography (hexane/EtOAc=5/1) to obtain 1-(diallylethoxysilyl)-4-(3,5-dimethyl-3-hydroxy-hexynyl)benzene (129.1 mg, 88% yield).