Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[NH2:8].[CH:9]1([O:14][C:15]2[CH:16]=[C:17]([CH:21]=[CH:22][C:23]=2[O:24][CH3:25])[C:18](Cl)=[O:19])[CH2:13][CH2:12][CH2:11][CH2:10]1>N1C=CC=CC=1.C(OCC)C>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[NH:8][C:18](=[O:19])[C:17]1[CH:21]=[CH:22][C:23]([O:24][CH3:25])=[C:15]([O:14][CH:9]2[CH2:10][CH2:11][CH2:12][CH2:13]2)[CH:16]=1
Reactant: COc1ccc(C(=O)Cl)cc1OC1CCCC1
Reactant: Nc1cnccc1Cl
Solvent: CCOCC
Solvent: c1ccncc1
Product: COc1ccc(C(=O)Nc2cnccc2Cl)cc1OC1CCCC1
Reaction time: 8 h
Yield: 59.2 %

Procedure:
A stirred solution of 4-chloropyrid-3-ylamine (1.94 g) and 3-cyclopentyloxy-4-methoxybenzoyl chloride (3.85 g) in pyridine (50 mL) is heated at 80° C. for 7 hours and then it is allowed to stand overnight. The reaction mixture is evaporated, to give a brown oil, which is subjected to mplc on silica gel, using diethyl ether as eluent, to give N-(4-chloropyrid-3-yl)-3-cyclopentyloxy-4-methoxybenzamide (3.1 g), m.p. 130°-132° C.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]([OH:6])=[O:5].[CH3:7][S:8](Cl)(=[O:10])=[O:9].[OH-].[Na+]>CO>[CH3:7][S:8]([NH:1][CH2:2][CH2:3][C:4]([OH:6])=[O:5])(=[O:10])=[O:9]
Reactant: CS(=O)(=O)Cl
Reactant: NCCC(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CS(=O)(=O)NCCC(=O)O
Reaction time: 3 h

Procedure:
22.3 g of β-alanine are dissolved in 125 ml of 2N MeOH. 20 ml of methanesulfonyl chloride and 145 ml of 2N NaOH are simultaneously added dropwise at 0°-5° C., with vibromixing, and the mixture is vibrated at room temperature for 3 hours. The solution is extracted with ether and the extract is diluted to 400 ml and stirred with a strongly acid ion exchanger (Lewatit® S 100) until the pH reaches about 2. The solution is then evaporated to dryness in vacuo. The residue is taken up in ethyl acetate, the mixture is dried over sodium sulfate and DCA is added until an alkaline reaction is obtained. The precipitate which separates out is filtered off, washed with ethyl acetate and ether, dried and recrystallized from tetrahydrofuran.
Reaction SMILES: Cl[CH2:2][C:3]1[C:7]2[CH:8]=[CH:9][C:10]([O:12][C:13]3[S:14][C:15]4[C:16]([N:21]=3)=[N:17][CH:18]=[CH:19][CH:20]=4)=[CH:11][C:6]=2[O:5][CH:4]=1.[N-:22]=[N+:23]=[N-:24].[Na+]>CN(C=O)C>[N:22]([CH2:2][C:3]1[C:7]2[CH:8]=[CH:9][C:10]([O:12][C:13]3[S:14][C:15]4[C:16]([N:21]=3)=[N:17][CH:18]=[CH:19][CH:20]=4)=[CH:11][C:6]=2[O:5][CH:4]=1)=[N+:23]=[N-:24]
Reactant: ClCc1coc2cc(Oc3nc4ncccc4s3)ccc12
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: [N-]=[N+]=NCc1coc2cc(Oc3nc4ncccc4s3)ccc12
Temperature: 25 °C
Reaction time: 3 h
Yield: 65.5 %

Procedure:
To a solution of 2-(3-chloromethyl-benzofuran-6-yloxy)-thiazolo[4,5-b]pyridine (2.7 g, 8.5 mmol) in DMF (42 mL) at 0° C. was added sodium azide (0.61 g, 9.3 mmol). The mixture was stirred at (rt, 3 h), partitioned between ethyl acetate and brine, dried, filtered and concentrated. Upon addition of ethyl acetate and hexanes, precipitate was formed and filtered. Concentration and purification by silica gel flash chromatography using ethyl acetate/hexanes provided a solid that was combined with the previously filtered precipitate to provide the title compound (1.8 g, 65%). MS (ESI): mass calcd. for C15H9N5O2S, 323.05; m/z found, 324.0 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.57 (dd, J=4.8, 1.6, 1H), 8.09-7.95 (m, 1H), 7.74-7.64 (m, 3H), 7.36 (dd, J=8.5, 2.1, 1H), 7.22 (dd, J=7.9, 4.8, 1H), 4.50 (s, 2H).
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]([O:10]C)=O)[CH2:4][CH2:3]1.O.[NH2:13][NH2:14]>C(O)C>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]([NH:13][NH2:14])=[O:10])[CH2:4][CH2:3]1
Reactant: COC(=O)C1CCN(C)CC1
Reactant: NN
Solvent: CCO
Solvent: O
Product: CN1CCC(C(=O)NN)CC1
Temperature: 120 °C
Yield: 72.5 %

Procedure:
In a 25 mL sealed tube, methyl 1-methylpiperidine-4-carboxylate (0.2 g, 1.0 eq.) was dissolved in ethanol (5 mL) at RT. Hydrazine hydrate (0.127 g, 2 eq.) was introduced dropwise at RT and the reaction mixture was heated at 120° C. for 20 h. The reaction mixture was concentrated under reduced pressure (40° C., 20 mm Hg) to afford the crude 1-methylpiperidine-4-carbohydrazide (0.145 g) which was used without further purification in the following step.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[Cl:10])[CH2:5]Cl.[NH2:11][CH:12]([CH3:15])[CH2:13][OH:14]>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[Cl:10])[CH2:5][NH:11][CH:12]([CH3:15])[CH2:13][OH:14]
Reactant: ClCc1ccc(Cl)c(Cl)c1
Reactant: CC(N)CO
Product: CC(CO)NCc1ccc(Cl)c(Cl)c1
Temperature: 50 °C
Reaction time: 2 h
Yield: 79 %

Procedure:
3,4-Dichlorobenzyl chloride (0.988 g) was added to 2-amino-1-propanol (4.10 g) and the mixture was stirred at 50° C. under nitrogen for 2 h. The mixture was partitioned between saturated aqueous sodium bicarbonate (100 ml) and ethyl acetate (100 ml) and the phases were separated. The organic layer was washed with water (4×100 ml) and brine, dried (Na2SO4) then concentrated under vacuum to give the title compound as a white solid (0.935 g).
Reaction SMILES: Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)=[CH:12][CH:11]=2)[N:3]=1.N1C=CC=CC=1C1C=CC(CO)=CC=1.[NH:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1.C([O-])([O-])=O.[K+].[K+].N1C=CC=CC=1C1C=CC(C=O)=CC=1>>[N:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[C:13]1[CH:14]=[CH:15][C:10]([CH2:9][O:8][C:4]2[CH:5]=[N:6][CH:7]=[C:2]([N:36]3[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]3)[N:3]=2)=[CH:11][CH:12]=1
Reactant: C1CNCCN1
Reactant: Clc1cncc(OCc2ccc(-c3ccccn3)cc2)n1
Agent: O=C([O-])[O-]
Agent: O=Cc1ccc(-c2ccccn2)cc1
Agent: OCc1ccc(-c2ccccn2)cc1
Product: c1ccc(-c2ccc(COc3cncc(N4CCNCC4)n3)cc2)nc1

Procedure:
The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-[{4-(2-pyridinyl)benzyl}oxy]pyrazine (2.73 g, 9.16 mmol; obtained according to the procedure of example 50, step 1, starting from 4-(2-pyridinyl)benzyl alcohol*), piperazine (2.41 g, 27.9 mmol) and K2CO3 (1.33 g, 9.62 mmol) with the exception that the final filtration through alumina was omitted. The yield of the of the title compound was 2.06 g (65%) which was obtained as a beige colored oil that solidified when refrigerated. Purity 100% (HPLC). MS m/z 347 (M)+. HRMS m/z calcd for C20H21N5O (M)+ 347.1746, found 347.1749. *Obtained by reduction (NaBH4) of 4-(2-pyridyl)benzaldehyde.
Reaction SMILES: CC(C)([O-:4])C.[K+].O.CN(OC)[C:10](=[O:18])[C@@H:11]([OH:17])[CH2:12][CH:13]1[CH2:16][CH2:15][CH2:14]1>C1COCC1>[OH:17][C@@H:11]([CH2:12][CH:13]1[CH2:16][CH2:15][CH2:14]1)[C:10]([OH:18])=[O:4]
Reactant: CC(C)(C)[O-]
Reactant: CON(C)C(=O)[C@@H](O)CC1CCC1
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)[C@@H](O)CC1CCC1
Temperature: 25 °C
Reaction time: 20 h
Yield: 85.3 %

Procedure:
A suspension of 33.66 g (0.3 mol) of potassium t-butoxide in 50 mL of THF was treated with 5.40 mL (0.3 mol) of H2O. The resulting mixture was treated with a solution of 11.48 g (0.061 mol) of N-methyl-N-methoxy 2-(S)-hydroxy-3-cyclobutyl propanamide (from Step C) in 20 mL of THF and stirred at rt for 20 h. The mixture was concentrated and the residue was partitioned between 300 mL of ether and 200 mL of H2O and the layers were separated. The pH of the aqueous layer was adjusted to 2 with concentrated HCl and extracted with 300 mL of EtOAc. The extract was washed with 100 mL of sat'd NaCl, dried over MgSO4 and concentrated to afford 7.50 g (85%) of the title compound: 1H NMR (500 MHz) δ1.66-1.76 (m, 2H), 1.78-1.98 (4H), 2.06-2.16 (m, 2H), 2.51-2.61 (m, 1H), 4.20 (dd, J=8.0,4.0, 1H).
Reaction SMILES: Cl[C:2]1[C:7]([C:8]2[N:13]=[N:12][C:11]([NH:14][CH2:15][C:16]3([C:20]4[C:25]([F:26])=[CH:24][CH:23]=[CH:22][N:21]=4)[CH2:19][CH2:18][CH2:17]3)=[CH:10][CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.O.[NH2:28][NH2:29].O1CCOCC1>C(OCC)(=O)C>[F:26][C:25]1[C:20]([C:16]2([CH2:15][NH:14][C:11]3[N:12]=[N:13][C:8]([C:7]4[C:2]([NH:28][NH2:29])=[N:3][CH:4]=[CH:5][CH:6]=4)=[CH:9][CH:10]=3)[CH2:19][CH2:18][CH2:17]2)=[N:21][CH:22]=[CH:23][CH:24]=1
Reactant: NN
Reactant: Fc1cccnc1C1(CNc2ccc(-c3cccnc3Cl)nn2)CCC1
Solvent: O
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: NNc1ncccc1-c1ccc(NCC2(c3ncccc3F)CCC2)nn1
Temperature: 160 °C

Procedure:
To a 5 mL microwave reaction vessel was added 6-(2-chloropyridin-3-yl)-N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)pyridazin-3-amine (750 mg, 2.0 mmol), hydrazine hydrate (1 mL), and dioxane (4 mL). The reaction was heated in a microwave reactor to 160° C. for 15 min, then diluted with ethyl acetate (50 mL), and washed with brine (20 mL). The organic layer was dried over Na2SO4, filtered, and concentrated to give a crude solid that was purified by reverse phase column chromatography to give 150 mg of N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)-6-(2-hydrazinylpyridin-3-yl)pyridazin-3-amine as an off-white solid. The isolated product was then dissolved in methanol and added to a vial containing ˜1 mL of Raney Nickel suspension in water. The mixture was then stirred under 50 psi of hydrogen for 2 h. The reaction was then filtered, concentrated, and purified by reverse phase column chromatography to give 10 mg (88%) of 6-(2-aminopyridin-3-yl)-N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)pyridazin-3-amine as an off-white solid, m/z=351.1 [M+H].
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[N:12]=[CH:11][C:10](Br)=[CH:9]2)([O-:3])=[O:2].[CH2:15]([Sn](CCCC)(CCCC)C=C)[CH2:16]CC>C(COC)OC.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>[N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[N:12]=[CH:11][C:10]([CH:15]=[CH2:16])=[CH:9]2)([O-:3])=[O:2]
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Reactant: O=[N+]([O-])c1cccc2cc(Br)cnc12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: COCCOC
Product: C=Cc1cnc2c([N+](=O)[O-])cccc2c1
Yield: 53.5 %

Procedure:
A mixture of 8-nitro-3-bromoquinoline (300 mg), tri-n-butyl(vinyl)tin (491 mg) and tetrakis(triphenylphosphine)palladium(0) (28 mg) in dimethoxyethane (6 ml) was refluxed for 1 hour. The mixture was concentrated in vacuo, and the residue was purified by column chromatography on silica gel (n-hexane-toluene) to give 8-nitro-3-vinylquinoline (127 mg).
Reaction SMILES: Cl.[S:2]([N:12]1[C:16]2=[N:17][CH:18]=[C:19]([CH2:21][NH2:22])[N:20]=[C:15]2[CH:14]=[CH:13]1)([C:5]1[CH:11]=[CH:10][C:8]([CH3:9])=[CH:7][CH:6]=1)(=[O:4])=[O:3].CCN(C(C)C)C(C)C.[C:32]([N:39]1[CH2:44][CH2:43][CH2:42][C@@H:41]([C:45](O)=[O:46])[CH2:40]1)([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.O>[S:2]([N:12]1[C:16]2=[N:17][CH:18]=[C:19]([CH2:21][NH:22][C:45]([C@@H:41]3[CH2:42][CH2:43][CH2:44][N:39]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:40]3)=[O:46])[N:20]=[C:15]2[CH:14]=[CH:13]1)([C:5]1[CH:6]=[CH:7][C:8]([CH3:9])=[CH:10][CH:11]=1)(=[O:3])=[O:4]
Reactant: Cc1ccc(S(=O)(=O)n2ccc3nc(CN)cnc32)cc1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H](C(=O)O)C1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(S(=O)(=O)n2ccc3nc(CNC(=O)[C@@H]4CCCN(C(=O)OC(C)(C)C)C4)cnc32)cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 100.4 %

Procedure:
To a solution of (5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanamine hydrochloride (5 g, 14.7 mmol) in DCM (78 mL) was added DIEA (7.7 mL, 44.3 mmol) and stirred at ambient temperature for about 10 min followed by the addition of (R)-N-Boc-piperidine-3-carboxylic acid (3.38 g, 14.7 mmol, CNH-Technologies) and HATU (5.61 g, 14.7 mmol). The mixture was stirred for about 1 h at ambient temperature and to it was added water (30 mL) and the layers were separated. The organic layer was washed with saturated aqueous NaHCO3 (30 mL) and brine (30 mL), dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 0-5% MeOH in DCM to afford crude (R)-tert-butyl 3-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methylcarbamoyl)piperidine-1-carboxylate (7.58 g, 94%): LC/MS (Table 1, Method b) Rt=2.30 min; MS m/z: 514 (M+H)+.
Reaction SMILES: [F:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[C:4]([F:9])[C:3]=1[NH:10][C:11]1[C:16]([C:17]2[N:25]=[CH:24][N:23]=[C:22]3[C:18]=2[N:19]=[CH:20][N:21]3[CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][O:27]2)=[CH:15][CH:14]=[CH:13][N:12]=1.[CH3:32][N:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][C:40]=2[S:42](Cl)(=[O:44])=[O:43])[CH:35]=[CH:34]1.N1C=CC=CC=1>ClCCl>[F:1][C:2]1[C:3]([NH:10][C:11]2[C:16]([C:17]3[N:25]=[CH:24][N:23]=[C:22]4[C:18]=3[N:19]=[CH:20][N:21]4[CH:26]3[CH2:31][CH2:30][CH2:29][CH2:28][O:27]3)=[CH:15][CH:14]=[CH:13][N:12]=2)=[C:4]([F:9])[CH:5]=[CH:6][C:7]=1[NH:8][S:42]([C:40]1[CH:39]=[CH:38][CH:37]=[C:36]2[C:41]=1[N:33]([CH3:32])[CH:34]=[CH:35]2)(=[O:43])=[O:44]
Reactant: Nc1ccc(F)c(Nc2ncccc2-c2ncnc3c2ncn3C2CCCCO2)c1F
Reactant: Cn1ccc2cccc(S(=O)(=O)Cl)c21
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cn1ccc2cccc(S(=O)(=O)Nc3ccc(F)c(Nc4ncccc4-c4ncnc5c4ncn5C4CCCCO4)c3F)c21
Temperature: 50 °C
Reaction time: 2 h

Procedure:
The 2,6-difluoro-N1-(3-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)benzene-1,3-diamine (20 mg, 0.047 mmol) prepared at Step 9 was added and dissolved into dichloromethane solvent. 1-methyl-1H-indole-7-sulfonyl chloride (16 mg, 0.07 mmol) and pyridine (8 uL, 0.094 mmol) were added into the reaction solution and stirred at 50° C. for 2 hours. After the reaction, the reactant was washed with 1N aqueous hydrochloric acid solution and salt water. After extraction with dichloromethane, the organic layer was dried with sulfuric anhydride magnesium and vacuum concentrated, and then refined by means of column chromatography, so that the target compound was obtained.
Reaction SMILES: C(O[C:4](=[N:15][OH:16])[CH2:5][C:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[O:8][N:7]=1)C.[NH3:17]>C(O)C>[O:8]1[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:6]([CH2:5][C:4](=[N:15][OH:16])[NH2:17])=[N:7]1
Reactant: CCOC(Cc1noc2ccccc12)=NO
Reactant: N
Solvent: CCO
Product: NC(Cc1noc2ccccc12)=NO
Temperature: 150 °C

Procedure:
In ethanol (35 ml) was dissolved 1,2-benzisoxazole-3-acetohydroximic acid ethyl ester (0.5 g) and the mixture was saturated with ammonia gas and then heated in a sealed tube at 150°C for 7 hours. The reaction mixture was distilled under a reduced pressure and the oily residue was subjected to silica gel column chromatography and eluted with 5 % methanol-chloroform. The eluates were collected and resulting crystallines were recrystallized from ethanol to give the desired compound (0.05 g). m.p. 160° to 162°C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:15]2[C:23]3[C:18](=[C:19]([CH2:25][S:26][CH3:27])[C:20]([F:24])=[CH:21][CH:22]=3)[NH:17][CH:16]=2)[CH2:9][C:10](OCC)=[O:11])=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C(#N)C.O>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:15]2[C:23]3[C:18](=[C:19]([CH2:25][S:26][CH3:27])[C:20]([F:24])=[CH:21][CH:22]=3)[NH:17][CH:16]=2)[CH2:9][CH2:10][OH:11])=[CH:6][CH:7]=1
Reactant: CCOC(=O)CC(c1ccc(Cl)cc1)c1c[nH]c2c(CSC)c(F)ccc12
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Solvent: CC#N
Product: CSCc1c(F)ccc2c(C(CCO)c3ccc(Cl)cc3)c[nH]c12
Temperature: 60 °C
Reaction time: 1 h

Procedure:
A solution of 2.33 g (5.7 mmol) of the compound from Example 47A in 18 ml of tetrahydrofuran was added dropwise to 20.1 ml (60.1 mmol) of a 1N solution of lithium aluminum hydride in tetrahydrofuran and 20 ml of tetrahydrofuran at RT. The mixture was stirred at 60° C. for 1 h, acetonitrile was added, and water was added to the solution while cooling in ice. The solid was filtered off with suction from the suspension, the filtrate was concentrated, and the residue was purified by preparative HPLC (mobile phase: acetonitrile/water gradient). 1.72 g (82% of theory) of the title compound were obtained.
Reaction SMILES: [CH2:1]([O:4][CH2:5][C:6]1[CH:11]=[C:10]([Cl:12])[C:9]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([CH2:20][CH3:21])=[CH:16][CH:15]=2)=[CH:8][C:7]=1[C@H:22]1[C@H:27]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C@@H:26]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C@H:25]([O:44][CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C@@H:24]([CH2:52][O:53][CH2:54][C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[O:23]1)[CH:2]=[CH2:3].CN(C=[O:65])C>[Pd](Cl)Cl.[Cu](Cl)Cl>[Cl:12][C:10]1[C:9]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([CH2:20][CH3:21])=[CH:18][CH:19]=2)=[CH:8][C:7]([C@H:22]2[C@H:27]([O:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C@@H:26]([O:36][CH2:37][C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)[C@H:25]([O:44][CH2:45][C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[C@@H:24]([CH2:52][O:53][CH2:54][C:55]3[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=3)[O:23]2)=[C:6]([CH:11]=1)[CH2:5][O:4][CH2:1][C:2](=[O:65])[CH3:3]
Reactant: CN(C)C=O
Reactant: C=CCOCc1cc(Cl)c(Cc2ccc(CC)cc2)cc1[C@@H]1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Agent: Cl[Cu]Cl
Agent: Cl[Pd]Cl
Product: CCc1ccc(Cc2cc([C@@H]3O[C@H](COCc4ccccc4)[C@@H](OCc4ccccc4)[C@H](OCc4ccccc4)[C@H]3OCc3ccccc3)c(COCC(C)=O)cc2Cl)cc1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 58.2 %

Procedure:
A mixture of palladium chloride (159 mg, 0.053 mmol) and copper chloride (267 mg, 0.27 mmol) in DMF (3 mL) was stirred for 2.5 h at room temperature. (2S,3S,4R,5R,6R)-2-(2-(allyloxymethyl)-4-chloro-5-(4-ethylbenzyl)phenyl)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)tetrahydro-2H-pyran (intermediate O-1) (300 mg, 0.36 mmol) was added to the mixture and stirred overnight under oxygen. The reaction mixture was filtered, the filtrate was poured into water and extracted with ethyl acetate (20 mL×3). The combined extracts were dried over Na2SO4, filtered, and evaporated to dryness. The residue was purified by preparative TLC, which afforded 1-(5-chloro-4-(4-ethylbenzyl)-2-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)benzyloxy)propan-2-one (intermediate T-1) (178 mg, 0.33 mmol, yield 58.2%). 1H-NMR (DMSO-d6, 300 MHz) δ 1.062 (t, J=8.1 Hz, 3H), 1.988 (s, 3H), 2.452 (dd, J=8.1 Hz, 2H), 3.603 (m, 6H), 3.793 (m, 2H), 3.997 (s, 2H), 4.125 (s, 2H), 4.491 (11, 7H), 4.744 (m, 4H), 6.789 (m, 2H), 7.015 (m, 4H), 7.169 (m, 5H), 7.288 (m, 13H), 7.457 (s, 2H).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[C:15]([CH3:16])=[CH:14][CH:13]=[CH:12][N:11]3[CH:17]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[Cl:25][CH2:26][CH2:27][CH2:28][S:29](Cl)(=[O:31])=[O:30]>CN(C)C=O>[CH3:16][C:15]1[C:10]2[N:11]([CH:17]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([NH:1][S:29]([CH2:28][CH2:27][CH2:26][Cl:25])(=[O:31])=[O:30])=[CH:7][CH:6]=3)[N:9]=2)[CH:12]=[CH:13][CH:14]=1
Reactant: O=S(=O)(Cl)CCCCl
Reactant: Cc1cccn2cc(-c3ccc(N)cc3)nc12
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cc1cccn2cc(-c3ccc(NS(=O)(=O)CCCCl)cc3)nc12
Temperature: 0 °C
Reaction time: 1.5 h

Procedure:
To a suspension of the product of Example 27 Step B (195 mg) in N,N-dimethylformamide (2 mL) was added triethylamine (0.12 mL) and the mixture cooled to 0° C. 3-chloropropanesulfonyl chloride (0.11 mL) was added dropwise and the mixture stirred for 1.5 hours before the addition of H20 (2 mL). The reaction mixture was partitioned between H2O (15 mL) and ethyl acetate (15 mL). The aqueous layer was brought to pH=9-10 with saturated sodium bicarbonate solution and extracted with ethyl acetate (2×). The combined organic layers were dried over magnesium sulfate, decanted, and evaporated. The residue was purified via silica gel chromatography (dichloromethane/methanol) to give the title compound (210 mg).
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7]2[C:9]([C:13]3[N:23]([S:24]([C:27]4[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=4)(=[O:26])=[O:25])[C:16]4[N:17]=[CH:18][CH:19]=[C:20]([CH:21]=O)[C:15]=4[CH:14]=3)=[CH:10][N:11]([CH3:12])[C:6]2=[CH:5][C:4]=1[O:34][CH3:35].Cl.Cl.[CH3:38][N:39]1[C:43]([CH2:44][CH2:45][NH2:46])=[CH:42][N:41]=[CH:40]1>>[CH3:1][O:2][C:3]1[N:8]=[C:7]2[C:9]([C:13]3[N:23]([S:24]([C:27]4[CH:28]=[CH:29][C:30]([CH3:33])=[CH:31][CH:32]=4)(=[O:25])=[O:26])[C:16]4=[N:17][CH:18]=[CH:19][C:20]([CH2:21][NH:46][CH2:45][CH2:44][C:43]5[N:39]([CH3:38])[CH:40]=[N:41][CH:42]=5)=[C:15]4[CH:14]=3)=[CH:10][N:11]([CH3:12])[C:6]2=[CH:5][C:4]=1[O:34][CH3:35]
Reactant: COc1cc2c(nc1OC)c(-c1cc3c(C=O)ccnc3n1S(=O)(=O)c1ccc(C)cc1)cn2C
Reactant: Cn1cncc1CCN
Agent: Cl
Product: COc1cc2c(nc1OC)c(-c1cc3c(CNCCc4cncn4C)ccnc3n1S(=O)(=O)c1ccc(C)cc1)cn2C
Yield: 95.4 %

Procedure:
The product is prepared by following the procedure described in example 34 stage (j) starting with 0.06 g of 2-(5,6-dimethoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-carbaldehyde and 0.05 g of 3-methylhistamine dihydrochloride instead of the cyclopropylamine used in example 34 stage (j). After purification by flash-pack chromatography (SiO2, dichloromethane/methanol 98/02 by volume as eluents), 0.070 g of [2-(5,6-dimethoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-ylmethyl]-[2-(3-methyl-3H-imidazol-4-yl)-ethyl]amine is obtained with the following characteristics:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[N:11]=[C:10]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.CC1(C)C(C)(C)OB([C:34]2[CH:47]=[CH:46][C:45]3[C:36](=[C:37]4[C:42](=[CH:43][CH:44]=3)[CH:41]=[CH:40][CH:39]=[N:38]4)[N:35]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:14]1([C:12]2[N:11]=[C:10]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:9]=[C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([C:39]4[CH:40]=[CH:41][C:42]5[C:37](=[C:36]6[C:45](=[CH:44][CH:43]=5)[CH:46]=[CH:47][CH:34]=[N:35]6)[N:38]=4)[CH:3]=3)[N:13]=2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: Brc1cccc(-c2nc(-c3ccccc3)nc(-c3ccccc3)n2)c1
Reactant: CC1(C)OB(c2ccc3ccc4cccnc4c3n2)OC1(C)C
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: C1CCOC1
Product: c1ccc(-c2nc(-c3ccccc3)nc(-c3cccc(-c4ccc5ccc6cccnc6c5n4)c3)n2)cc1
Temperature: 25 °C

Procedure:
In a stream of argon, 1.20 g of 2-(3-bromophenyl)-4,6-diphenyl-1,3,5-triazine, 1.30 g of 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,10-phenanthroline, 1.11 g of cesium carbonate, 14 mg of palladium acetate and 32 mg of triphenylphosphine were suspended in 140 mL of tetrahydrofuran. The suspension was heated under reflux for 19 hours. Then the reaction mixture was left to be cooled to room temperature, and distilled under a reduced pressure to remove low-boiling point ingredients. Methanol was added to the residue, and the deposited solid was collected by filtration. The thus-obtained crude product was purified by silica gel column chromatography using a methanol/chloroform (1:100 to 1:77) mixed solvent as a developing solvent to give 1.37 g of target 4,6-diphenyl-2-[3-(1,10-phenanthrolin-2-yl)phenyl]-1,3,5-triazine as a white solid (yield, 91%).