Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:10]([C:11]#[C:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([NH:19][C:20]([C:22]3[O:23][CH:24]=[CH:25][C:26]=3[CH3:27])=[O:21])[CH:14]=2)=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][N:3]=1.CCN=C=NCCCN(C)C.[CH3:39][S:40]([C:43]1[CH:48]=[CH:47][C:46]([CH2:49][CH2:50][C:51]([O:53][CH3:54])=[O:52])=[CH:45][CH:44]=1)(=[NH:42])=[O:41]>CN(C=O)C.CN(C1C=CN=CC=1)C.CCOC(C)=O>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:6]([N:42]=[S:40]([C:43]2[CH:44]=[CH:45][C:46]([CH2:49][CH2:50][C:51]([O:53][CH3:54])=[O:52])=[CH:47][CH:48]=2)([CH3:39])=[O:41])=[O:7])=[CH:9][C:10]=1[C:11]#[C:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([NH:19][C:20]([C:22]2[O:23][CH:24]=[CH:25][C:26]=2[CH3:27])=[O:21])[CH:14]=1
Reactant: COC(=O)CCc1ccc(S(C)(=N)=O)cc1
Reactant: Cc1ccoc1C(=O)Nc1cccc(C#Cc2cc(C(=O)O)cnc2N)c1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COC(=O)CCc1ccc(S(C)(=O)=NC(=O)c2cnc(N)c(C#Cc3cccc(NC(=O)c4occc4C)c3)c2)cc1
Temperature: 60 °C
Reaction time: 0.33 h
Yield: 37 %

Procedure:
6-Amino-5-((3-(3-methylfuran-2-carboxamido)phenyl)ethynyl)nicotinic acid (0.1 g, 0.277 mmol) was dissolved in DMF (2.8 mL). EDCI (0.64 g, 0.332 mmol) and DMAP (3.42 mg, 0.028 mmol) were then added and the reaction mixture was stirred at 60° C. for 20 minutes. Methyl 3-(4-(S-methylsulfonimidoyl)-phenyl)propanoate (0.068 g, 0.277 mmol) was then added, and the reaction was allowed to stir for 3 hours at 60° C. The mixture was cooled to room temperature then taken up in EtOAc (10 mL) and extracted with brine (3×10 mL). The organic layer was dried over anhydrous Na2SO4(s), filtered and concentrated in vacuo. The crude product was then purified over silica purified via column chromatography (gradient eluant mixture of MeOH in EtOAc: 0% to 10% MeOH) to give the title compound (0.060 g, 37%).
Reaction SMILES: [CH:1]1[N:6]=[C:5](Cl)[C:4]2[N:8]=[CH:9][N:10]([C@@H:11]3[O:15][C@H:14]([CH2:16][OH:17])[C@@H:13]([OH:18])[C@H:12]3[OH:19])[C:3]=2[N:2]=1.[CH3:20][C:21]1[N:22]=[CH:23][NH:24][C:25]=1[CH2:26][S:27][CH2:28][CH2:29][NH2:30].C(N(CC)CC)C>C(O)C>[CH3:20][C:21]1[N:22]=[CH:23][NH:24][C:25]=1[CH2:26][S:27][CH2:28][CH2:29][NH:30][C:5]1[C:4]2[N:8]=[CH:9][N:10]([C:3]=2[N:2]=[CH:1][N:6]=1)[C@@H:11]1[O:15][C@H:14]([CH2:16][OH:17])[C@@H:13]([OH:18])[C@H:12]1[OH:19]
Reactant: OC[C@H]1O[C@@H](n2cnc3c(Cl)ncnc32)[C@H](O)[C@@H]1O
Reactant: Cc1nc[nH]c1CSCCN
Solvent: CCN(CC)CC
Solvent: CCO
Product: Cc1nc[nH]c1CSCCNc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O

Procedure:
5.0 g of 6-chloropurine riboside (0.0179 moles) 4.6 g of 4-methyl-5-[(2 aminoethyl)-thiomethyl]-imidazole (0.019 moles), and 8.78 ml of triethylamine (0.063 moles) are refluxed overnight in 100 ml of ethanol. 15 ml of solvent are then removed with nitrogen gas. The crystals formed therefrom are filtered and washed with ethanol. The crystals are then recrystallized from ethanol and washed with diethyl ether.
Reaction SMILES: C[O:2][C:3](=[O:31])[CH2:4][CH:5]1[CH2:10][NH:9][C@H:8]([C:11]([N:13]2[CH2:17][CH2:16][CH:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:14]2)=[O:12])[C@@H:7]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:6]1.[OH-].[Li+]>C1COCC1>[C:27]([O:26][C:24]([C@@H:7]1[C@@H:8]([C:11]([N:13]2[CH2:17][CH2:16][CH:15]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH2:14]2)=[O:12])[NH:9][CH2:10][CH:5]([CH2:4][C:3]([OH:31])=[O:2])[CH2:6]1)=[O:25])([CH3:30])([CH3:28])[CH3:29]
Reactant: COC(=O)CC1CN[C@H](C(=O)N2CCC(c3ccccc3)C2)[C@@H](C(=O)OC(C)(C)C)C1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)[C@H]1CC(CC(=O)O)CN[C@@H]1C(=O)N1CCC(c2ccccc2)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 87 %

Procedure:
A solution of tert-butyl (2S,3S)-5-(2-methoxy-2-oxoethyl)-2-[(3-phenylpyrrolidin-1-yl)carbonyl]piperidine-3-carboxylate in THF (3 mL) was cooled to 0° C. prior to the addition of lithium hydroxide (7 mg, 0.16 mmol). After warming to ambient temperature, the reaction mixture was stirred overnight. The volatiles were removed in-vacuo to afford 60 mg (87%) of {(5S,6S)-5-(tert-butoxycarbonyl)-6-[(3-phenylpyrrolidin-1-yl)carbonyl]piperidin-3-yl}acetic acid as an off-white solid that was used without neutralization and purification in the following coupling reaction. MS (ESI): 417 (M+H+).
Reaction SMILES: [CH3:1][C:2]1[C:3]2[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=2[S:5][C:6]=1[CH:7]=O.CN.CC(O)=O.[C:19]([BH3-])#[N:20].[Na+]>CO>[CH3:1][C:2]1[C:3]2[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=2[S:5][C:6]=1[CH2:7][NH:20][CH3:19]
Reactant: [BH3-]C#N
Reactant: Cc1c(C=O)sc2ccccc12
Agent: CN
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: CNCc1sc2ccccc2c1C
Temperature: 25 °C
Yield: 56 %

Procedure:
To a stirred solution of 3-methylbenzo[b]thiophene-2-carboxaldehyde (0.5 g, 2.8 mmole) in methanol (15 mL) was added 2.0 M methylamine in methanol (6 mL, 12 mmole) and HOAc (0.32 mL, 5.7 mmole). The reaction was stirred at RT for hr, then sodium cyanoborohydride (0.2 g, 3 mmole) was added in one portion. After stirring for an additional 16 hr the reaction was concentrated to dryness. The residue was taken up in Et2O and washed with 1.0 N NaOH then with brine, dried (Na2SO4), and concentrated under vacuum. Purification by flash chromatography on silica gel (95:5 CHCl3/methanol containing 5% NH4OH) gave the title compound (0.30 g, 56%) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J=7.8 Hz,1H), 7.62 (d, J=7.9 Hz, 1H), 7.34 (t,1H), 7.28 (t,1H), 3.99 (s, 2H), 2.49 (s, 3H), 2.34 (s, 3H), 1.77 (br s,1H).
Reaction SMILES: [CH2:1]1[O:11][C:4]2([CH2:9][CH2:8][C:7](=[O:10])[CH2:6][CH2:5]2)[O:3][CH2:2]1.[BH4-].[Na+]>C(O)C>[O:3]1[C:4]2([CH2:9][CH2:8][CH:7]([OH:10])[CH2:6][CH2:5]2)[O:11][CH2:1][CH2:2]1
Reactant: O=C1CCC2(CC1)OCCO2
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: OC1CCC2(CC1)OCCO2
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A solution of 15.6 grams (0.10 mole) of 1,4-cyclohexanedione mono-ethylene ketal in about 40 mL of ethanol is stirred, and 1.9 grams (0.05 mole) of sodium borohydride is added portionwise during a one hour period. Upon completion of addition, the reaction mixture is stirred at ambient temperature for about four hours. After this time the reaction mixture is concentrated under reduced pressure to a residue. The residue is taken up in about 40 mL of water, and the mixture is extracted with three 25 mL portions of diethyl ether. The combined extracts are washed with an aqueous solution saturated with sodium chloride. The organic layer is then dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, yielding 1,4-dioxaspiro-[4.5]decan-8-ol
Reaction SMILES: Br[C:2]1[CH:17]=[CH:16][C:5]([CH2:6][CH2:7][NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:4][C:3]=1[O:18][C:19]([F:22])([F:21])[F:20].C(=O)([O-])O.[Na+].[CH3:28][N:29](C=O)C>[C-]#N.[Zn+2].[C-]#N.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>[C:28]([C:2]1[CH:17]=[CH:16][C:5]([CH2:6][CH2:7][NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:4][C:3]=1[O:18][C:19]([F:22])([F:21])[F:20])#[N:29]
Reactant: CN(C)C=O
Reactant: CC(C)(C)OC(=O)NCCc1ccc(Br)c(OC(F)(F)F)c1
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: [C-]#N
Product: CC(C)(C)OC(=O)NCCc1ccc(C#N)c(OC(F)(F)F)c1
Temperature: 160 °C
Reaction time: 1 h
Yield: 38 %

Procedure:
A mixture of tert-butyl 4-bromo-3-(trifluoromethoxy)phenethylcarbamate (460 mg, 1.2 mmol), zinc cyanide (463 mg, 1.56 mmol) and tetrakis(triphenylphosphine)palladium (69 mg, 0.06 mmol) in DMF (10 mL) was stirred at 160° C. for 1 h under nitrogen. The reaction was treated with saturated sodium hydrogen carbonate and extracted with ethyl acetate (30 mL×3). The combined organic layers were washed with brine, dried, concentrated and purified by preparative thin layer chromatography (2.9% MeOH in DCM) to afford the title compound (150 mg, 0.45 mmol, 38% yield). MS (ESI) m/z 331.1 [M+1]+.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:46]([C:49]1[CH:54]=[CH:53][C:52]([CH2:55][CH:56]([NH2:60])[C:57]([OH:59])=[O:58])=[CH:51][C:50]=1[NH2:61])(=[O:48])[CH3:47]>CN(C=O)C>[C:46]([C:49]1[CH:54]=[CH:53][C:52]([CH2:55][CH:56]([NH:60][C:8](=[O:10])[C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:12][CH:11]=2)[C:57]([OH:59])=[O:58])=[CH:51][C:50]=1[NH2:61])(=[O:48])[CH3:47]
Reactant: CC(=O)c1ccc(CC(N)C(=O)O)cc1N
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(=O)c1ccc(CC(NC(=O)c2ccc([N+](=O)[O-])cc2)C(=O)O)cc1N
Reaction time: 0.5 h

Procedure:
To 4-nitrobenzoic acid (50.1 mg), HATU (114 mg) and DIEA (105 μL) was added 1 mL DMF and the mixture was stirred for 30 minutes. Then the resulting solution was added to 3-(4-acetyl-3-aminophenyl)-2-aminopropanoic acid (66.7 mg, 1.0 equiv) in 1.0 mL DMF, and the reaction was stirred at room temperature, monitored by LC-MS. The title product was then isolated by preparative HPLC. 1H NMR (400 MHz, MeOD): δ 8.28 (d, J=8.8 Hz, 2H), 7.93 (d, J=8.8 Hz, 2H), 7.72 (d, J=8.4 Hz, 1H), 6.69 (d, J=1.6 Hz, 1H), 6.61 (dd, J′=8.4 Hz, J″=1.6 Hz, 1H), 3.28 (dd, J′=13.8 Hz, J″=10.0 Hz, 1H), 3.02 (dd, J′=13.8 Hz, J″=10.0 Hz, 1H), 2.51 (s, 3H); ESI-MS (m/z) 372.34 (MH+).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:17]=[C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:15]([C:26]([CH3:28])=[CH2:27])=[CH:14][C:10]=1[C:11](O)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.Cl.Cl.[CH2:45]1[C:53]2[C:48](=[CH:49][C:50]([C:54]3([OH:61])[CH2:59][CH2:58][N:57]([CH3:60])[CH2:56][CH2:55]3)=[CH:51][CH:52]=2)[CH2:47][NH:46]1.C(N(CC)CC)C>C(Cl)Cl.C1COCC1.CN(C=O)C.CCOC(C)=O>[CH2:1]([O:8][C:9]1[CH:17]=[C:16]([O:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:15]([C:26]([CH3:28])=[CH2:27])=[CH:14][C:10]=1[C:11]([N:46]1[CH2:47][C:48]2[C:53](=[CH:52][CH:51]=[C:50]([C:54]3([OH:61])[CH2:59][CH2:58][N:57]([CH3:60])[CH2:56][CH2:55]3)[CH:49]=2)[CH2:45]1)=[O:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C=C(C)c1cc(C(=O)O)c(OCc2ccccc2)cc1OCc1ccccc1
Reactant: CN1CCC(O)(c2ccc3c(c2)CNC3)CC1
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: C1CCOC1
Product: C=C(C)c1cc(C(=O)N2Cc3ccc(C4(O)CCN(C)CC4)cc3C2)c(OCc2ccccc2)cc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 55.2 %

Procedure:
A solution of 2,4-bis-benzyloxy-5-isopropenyl-benzoic acid (145 mg; 1.2 equiv.) in DCM (5 ml) was treated with EDC (80 mg; 1.3 equiv.) and HOAt (66 mg; 1.5 equiv.) then stirred at room temperature for 30 minutes. This solution was then added to a mixture of 4-(2,3-dihydro-1H-isoindol-5-yl)-1-methyl-piperidin-4-ol dihydrochloride (112 mg; 0.32 mmol) and triethylamine (90 μl; 2 equiv.) in THF (5 ml) and DMF (2 ml), the reaction was then stirred at room temperature overnight. The reaction mixture was diluted with EtOAc, washed with water, 1N NaOH and brine, the EtOAc layer was separated, dried (MgSO4) and evaporated. Purification by flash column chromatography on SiO2, gradient elution from 0% to 5% 2M methanolic ammonia/DCM gave 104 mg of (2,4-bis-benzyloxy-5-isopropenyl-phenyl)-[5-(4-hydroxy-1-methyl-piperidin-4-yl)-1,3-dihydro-isoindol-2-yl]-methanone as a yellow glass.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.Cl[CH2:16][CH2:17][O:18][C:19](=[O:23])[C:20]([O-])=[O:21]>C(Cl)Cl>[O:21]=[C:20]([NH:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1)[C:19]([O:18][CH2:17][CH3:16])=[O:23]
Reactant: Nc1cccnc1
Reactant: O=C([O-])C(=O)OCCCl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)C(=O)Nc1cccnc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 82 %

Procedure:
To a solution 3-aminopyridine (3.00 g, 27.0 mmol) in methylene chloride (110 mL) at 23 ° C. was added triethylamine (7.53 mL, 54.0 mmol) and N,N-dimethylarninopyridine (330 mg, 2.70 mmol). The solution was cooled to 0° C. and chloroethyloxalate 4.42 g, 32.4 mmol) was added in a dropwise fashion. The reaction mixture was stirred at 0° C. for 2 hours and then quenched with water (30 mL) and partitioned. The organic portion was washed with 10% sodium bicarbonate solution (30 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to provide 4.30 g of the title compound.
Reaction SMILES: O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.OP(O)(O)=O.N1C(C(N)=O)=CN=C1.[NH2:28][C:29]1[C:34]([NH:35][C:36]([C:38]2[N:39]=[CH:40][N:41](COCC[Si](C)(C)C)[C:42]=2[C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=O)=[C:33]([NH2:57])[N:32]=[CH:31][N:30]=1.N>>[C:43]1([C:42]2[N:41]=[CH:40][NH:39][C:38]=2[C:36]2[NH:28][C:29]3[C:34]([N:35]=2)=[C:33]([NH2:57])[N:32]=[CH:31][N:30]=3)[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1
Reactant: C[Si](C)(C)CCOCn1cnc(C(=O)Nc2c(N)ncnc2N)c1-c1ccccc1
Agent: N
Agent: NC(=O)c1cnc[nH]1
Agent: O=P(O)(O)O
Product: Nc1ncnc2[nH]c(-c3[nH]cnc3-c3ccccc3)nc12
Temperature: 160 °C
Yield: 6.1 %

Procedure:
P2O5 (0.29 g) and H3PO4 (0.21 mL) were added to a mixture of N-(4,6-diaminopyrimidin-5-yl)-4-phenyl-1-{[2- trimethylsilyl)ethoxy]methyl}-1H-imidazole-5-carboxamide and N-(4,6-diaminopyrimidin-5-yl)-5-phenyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole-4-carboxamide (Intermediate 36) (65 mg) and heated at 160° C. for 24 hours. After cooling to ambient temperature, ice was added and the reaction mixture adjusted to pH 5 with NH3 solution. The solvent was evaporated in vacuo to give a yellow oil. Purification by preparative RPHPLC (MeCN:water:TFA, 90:10:0.1) gave the title compound as a colourless solid (2.6 mg, 6%);
Reaction SMILES: [C:1]([C:3]1[CH:4]=[CH:5][C:6](Cl)=[N:7][CH:8]=1)#[N:2].[C:10]1(B(O)O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCOC(C)=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>[C:10]1([C:6]2[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][N:7]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: OB(O)c1ccccc1
Reactant: N#Cc1ccc(Cl)nc1
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: Cc1ccccc1
Solvent: CCOC(C)=O
Product: N#Cc1ccc(-c2ccccc2)nc1
Yield: 93.8 %

Procedure:
5-Cyano-2-chloropyridine (5.0 g, 36.1 mmol), phenylboronic acid (6.6 g, 54 mmol), tetrakis(triphenylphosphine)palladium (0) (0.5 g), and aqueous Na2CO3 (7.6 g), in toluene (100 mL) were heated at 90° C. for 16 h. The mixture was diluted with EtOAc and washed with H2O. The organic layer was dried (MgSO4), filtered, and concentrated. The residue was purified by silica gel chromatography (hexanes/EtOAc 2/1) to afford the title compound (6.1 g, 94%). MS (ESI) m/z 181 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[C:7](Br)[CH:8]=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:13]([NH:15][CH2:16][CH2:17][CH3:18])=[O:14].[N:19]1[CH:24]=[CH:23][CH:22]=[C:21](B(O)O)[CH:20]=1>>[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([C:21]3[CH:20]=[N:19][CH:24]=[CH:23][CH:22]=3)[CH:8]=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:13]([NH:15][CH2:16][CH2:17][CH3:18])=[O:14]
Reactant: CCCNC(=O)c1nnc2c(Br)cccc2c1N
Reactant: OB(O)c1cccnc1
Product: CCCNC(=O)c1nnc2c(-c3cccnc3)cccc2c1N
Yield: 76.9 %

Procedure:
Using method A, 4-amino-8-bromo-N-propyl-cinnoline-3-carboxamide (200 mg, 0.647 mmol) and pyridin-3-ylboronic acid (160 mg, 1.301 mmol) were reacted to afford the title compound (153 mg, 74% yield) as an off-white solid. 1H NMR (300 MHz, CDCl3) δ 8.89 (m, 1H), 8.68 (m, 1H), 8.54 (br, 1H), 8.13 (m, 1H), 7.93 (m, 1H), 7.85-7.73 (m, 2H), 7.44 (m, 1H), 3.47 (apparent quartet, J=7.0 Hz, 2H), 1.68 (apparent sextet, J=7.0 Hz, 2H), 1.01 (t, J=7.0 Hz, 3H). MS APCI, m/z=308 (M+H) HPLC 1.46 min.
Reaction SMILES: Cl.FC1C=C(C=CC=1)CN1C=C(C2C3C(=NC=C(C4C=CC(C5CCNCC5)=CC=4)C=3)N(S(C3C=CC(C)=CC=3)(=O)=O)C=2)C=N1.[F:46][C:47]1[CH:48]=[C:49]([CH:91]=[CH:92][CH:93]=1)[CH2:50][N:51]1[CH:55]=[C:54]([C:56]2[C:64]3[C:59](=[N:60][CH:61]=[C:62]([C:65]4[CH:66]=[N:67][C:68]([N:71]5[CH2:76][CH2:75][N:74]([CH2:77][CH:78]([CH3:80])[CH3:79])[CH2:73][CH2:72]5)=[CH:69][CH:70]=4)[CH:63]=3)[N:58](S(C3C=CC(C)=CC=3)(=O)=O)[CH:57]=2)[CH:53]=[N:52]1.[OH-].[Li+]>C1COCC1.CO.O>[F:46][C:47]1[CH:48]=[C:49]([CH:91]=[CH:92][CH:93]=1)[CH2:50][N:51]1[CH:55]=[C:54]([C:56]2[C:64]3[C:59](=[N:60][CH:61]=[C:62]([C:65]4[CH:66]=[N:67][C:68]([N:71]5[CH2:72][CH2:73][N:74]([CH2:77][CH:78]([CH3:79])[CH3:80])[CH2:75][CH2:76]5)=[CH:69][CH:70]=4)[CH:63]=3)[NH:58][CH:57]=2)[CH:53]=[N:52]1
Reactant: Cc1ccc(S(=O)(=O)n2cc(-c3cnn(Cc4cccc(F)c4)c3)c3cc(-c4ccc(N5CCN(CC(C)C)CC5)nc4)cnc32)cc1
Agent: Cc1ccc(S(=O)(=O)n2cc(-c3cnn(Cc4cccc(F)c4)c3)c3cc(-c4ccc(C5CCNCC5)cc4)cnc32)cc1
Agent: Cl
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: CC(C)CN1CCN(c2ccc(-c3cnc4[nH]cc(-c5cnn(Cc6cccc(F)c6)c5)c4c3)cn2)CC1
Yield: 15 %

Procedure:
Using similar reaction conditions as described in step-iii of example-1, 3-(1-(3-fluorobenzyl)-1H-pyrazol-4-yl)-5-(6-(4-isobutylpiperazin-1-yl)pyridin-3-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine (70 mg, 0.105 mmol) was hydrolyzed by lithium hydroxide (27 mg, 0.632 mmol) in THF/methanol/water (3/2/1 ml) to yield 8 mg (15.0% yield) of the titled compound. 1H NMR (CDCl3, 300 MHz): δ 8.83 (s, 1H), 8.49-8.45 (dd, 2H), 8.11-8.10 (d, 1H), 7.85 (s, 1H), 7.76-7.69 (m, 2H), 7.42-7.41 (d, 1H), 7.39-7.30 (m, 1H), 7.10-6.90 (m, 3H), 6.77-6.74 (d, 1H), 5.38 (s, 2H), 3.60-3.59 (t, 4H), 2.60-2.50 (t, 4H), 2.16-2.14 (d, 2H), 1.90-1.80 (m, 1H), 0.95-0.93 (d, 6H). MS: m/z=510.3 (M+1), HPLC: 93.26% in method A.
Reaction SMILES: I[C:2]1[C:10]2[N:9]3[CH:11]=[CH:12][CH:13]=[C:8]3[C:7](=[O:14])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[N:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[C:17](B(O)O)[CH:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[N:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[C:17]([C:2]2[C:10]3[N:9]4[CH:11]=[CH:12][CH:13]=[C:8]4[C:7](=[O:14])[C:6]=3[CH:5]=[CH:4][CH:3]=2)[CH:16]=1
Reactant: OB(O)c1cnc2ccccc2c1
Reactant: O=C1c2cccc(I)c2-n2cccc21
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: O=C1c2cccc(-c3cnc4ccccc4c3)c2-n2cccc21
Temperature: 123 °C
Reaction time: 3 h
Yield: 63.7 %

Procedure:
In a 100 ml round-bottomed flask under argon, a mixture of 361 mg of 5-iodopyrrolo[1,2-a]indol-9-one (which can be prepared according to J. Med. Chem. 2004, 47(6), 1448), 214 mg of 3-quinolineboronic acid, 603 mg of caesium carbonate and 143 mg of tetrakis(triphenylphosphine)palladium(O) in 20 ml of dimethylformamide is heated at 123° C. After 3 hours, the reaction medium is evaporated to dryness under vacuum and the residue is taken up in ethyl acetate and filtered. The filtrate is washed with water, twice with a saturated solution of sodium bicarbonate and then with a saturated solution of sodium chloride, dried with magnesium sulphate, and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (15-40 μm), elution being carried out with a gradient of ethyl acetate (20% to 30% v/v) in n-heptane. 231 mg of 5-quinolin-3-ylpyrrolo[1,2-a]indol-9-one are obtained in the form of a solid, the characteristics of which are the following:
Reaction SMILES: [O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH2:9]([NH:16][C:17]([NH2:19])=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.Br[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CNCCNC>[Cu]I.O1CCOCC1>[CH2:9]([NH:16][C:17]([NH:19][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: Brc1ccccc1
Reactant: NC(=O)NCc1ccccc1
Agent: [Cu]I
Agent: CNCCNC
Agent: O=P([O-])([O-])[O-]
Solvent: C1COCCO1
Product: O=C(NCc1ccccc1)Nc1ccccc1
Temperature: 80 °C
Reaction time: 25 h
Yield: 79.1 %

Procedure:
A test tube was charged with CuI (20 mg, 0.10 mmol, 0.10 equiv), K3PO4 (425 mg, 2.0 mmol, 2.0 equiv), benzylurea (225 mg, 1.5 mmol, 1.5 equiv), filled with argon. Bromobenzene (105 μL, 1.0 mmol, 1.0 equiv), N,N′-dimethylethylendiamine (22 μL, 0.20 mmol, 0.20 equiv) and dry dioxane (1.0 mL) were added under argon. The test tube was sealed and the reaction mixture was stirred at 80° C. for 25 h. The resulting suspension was cooled to room temperature and filtered through a 0.5×1 cm pad of silica gel, eluting with ethyl acetate. The filtrate was concentrated in vacuo. The solid residue was dissolved in ˜2 mL DMF. Purification of the residue by flash chromatography on silica gel (2×20 cm; hexane:ethyl acetate 3:1) provided 179 mg (79% yield) of the title compound as a white solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[CH:11][CH:10]=[C:9]2[C:13]2[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.[Xe](F)[F:24].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[F:24][C:12]1[N:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[C:9]([C:13]2[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:14]=2)=[CH:10][CH:11]=1
Reactant: CS(=O)(=O)c1ccc(-c2cccn2-c2ccc(F)cc2)cc1
Reactant: F[Xe]F
Agent: *CC*
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Product: CS(=O)(=O)c1ccc(-c2ccc(F)n2-c2ccc(F)cc2)cc1
Yield: 35.6 %

Procedure:
0.90 g (2.7 mmol) of 1-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)pyrrole (prepared as described in Example 33) was dissolved in 10 ml of acetonitrile in a reaction vessel made of polyethylene, and 0.46 g (2.7 mmol) of xenon difluoride was added to the resulting solution at 0° C., whilst stirring. The temperature of the reaction mixture was then allowed to return to room temperature, and the mixture was stirred at room temperature for 20 hours. At the end of this time, 20 ml of a saturated aqueous solution of sodium carbonate was added to the mixture, which was then extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium carbonate and then with water, after which it was dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure. The resulting residue was applied to a silica gel chromatography column and eluted with a 3:1 by volume mixture of hexane and ethyl acetate, to give 0.32 g of the title compound as white prismatic crystals (yield 34%), melting at 140-141° C.
Reaction SMILES: Br[C:2]1[N:3]=[CH:4][N:5]([C:7]2[N:12]=[C:11]([CH3:13])[CH:10]=[C:9]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[N:8]=2)[CH:6]=1.CC1(C)C(C)(C)OB([C:32]2[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=2)O1>>[CH3:13][C:11]1[CH:10]=[C:9]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[N:8]=[C:7]([N:5]2[CH:6]=[C:2]([C:32]3[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=3)[N:3]=[CH:4]2)[N:12]=1
Reactant: CC1(C)OB(c2cccnc2)OC1(C)C
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(-n2cnc(Br)c2)n1
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(-n2cnc(-c3cccnc3)c2)n1

Procedure:
The title compound was prepared from 2-(4-bromo-imidazol-1-yl)-4-methyl-6-(4-trifluoromethyl-phenyl)-pyrimidine (example E.13) (0.31 g, 0.8 mmol) and commercially available 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.16 g, 0.8 mmol) according to the general procedure VI. Obtained as an off-white solid (0.012 g, 4%). MS (ISP) 382.3 [(M+H)+]; mp 208-210° C.