Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:7]=[O:8])[O:5][CH:6]=1.[C:9]1(B(O)O)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C([O-])([O-])=O.[K+].[K+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>COCCOC.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]>[CH:7]([C:4]1[O:5][CH:6]=[C:2]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:3]=1)=[O:8]
Reactant: OB(O)c1ccccc1
Reactant: O=Cc1cc(Br)co1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: O=C([O-])[O-]
Solvent: COCCOC
Product: O=Cc1cc(-c2ccccc2)co1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 41.3 %

Procedure:
Prepare a solution of 4-bromo-2-formylfuran (3.7 g, 21.1 mmol) in 1,2-dimethoxyethane (148 mL). Add phenyl boronic acid (5.16 g, 42.3 mmol), K2CO3 (31.6 mL, 63.4 mmol), Pd2(dba)3 (660 mg, 0.63 mmol), and PPh3 (670 mg, 2.5 mmol). Stir the reaction mixture under nitrogen for 10 minutes at room temperature. After 10 minutes, heat the mixture to 80° C. for 3 days. Wash the reaction mixture with brine (30 mL), dry (Na2SO4), filter, and concentrate. Perform flash chromatography on silica gel eluting with 1:1 hex/ethyl acetate to afford the title compound (1.5 g) as a brown liquid. 1H NMR (CDCl3) δ 9.71 (s, 1H), 7.97 (s, 1H), 6.82-7.55 (m, 6H).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]2[N:9]([C:13]3[C:18]([CH3:19])=[CH:17][C:16]([CH3:20])=[CH:15][C:14]=3[CH3:21])[N:10]=[C:11]([CH3:12])[C:3]=12.N[C@@H](CC)CO.[C:28]1([OH:34])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>>[CH3:12][C:11]1[C:3]2[C:4](=[N:5][C:6]([CH3:8])=[CH:7][C:2]=2[O:34][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:9]([C:13]2[C:18]([CH3:19])=[CH:17][C:16]([CH3:20])=[CH:15][C:14]=2[CH3:21])[N:10]=1
Reactant: Cc1cc(C)c(-n2nc(C)c3c(Cl)cc(C)nc32)c(C)c1
Reactant: Oc1ccccc1
Agent: CC[C@H](N)CO
Product: Cc1cc(C)c(-n2nc(C)c3c(Oc4ccccc4)cc(C)nc32)c(C)c1
Temperature: 190 °C
Yield: 14.5 %

Procedure:
A mixture of 4-chloro-3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridine (300 mg, 1 mmol), (S)-2-amino-1-butanol (107 mg, 1.2 mmol) and phenol (188 mg, 2 mmol) was heated in 190° C. oil bath for 15 hours. The mixture was cooled, quenched with 2 N sodium hydroxide and extracted with chloroform. The organic layer was separated and neutralized with 2 N hydrochloride and water. The organic layer was dried and concentrated to give an oil residue. The residue was purified through silica gel column chromatography using chloroform as eluent to give 157 mg of starting material, and 52 mg of 3,6-dimethyl-4-phenoxy-1-(2,4,6-trimethylphenyl)-1H-pyrazolo-[3,4-b]pyridine as beige crystals. 1H NMR (CDCl3): 7.1-7.45 (m, 5H), 6.95 (s, 2H), 6.06 (s, 1H), 2.71 (s, 3H), 2.38 (s, 3H), 2.29 (S, 3H), 1.94 (s, 6H) ppm; and 30 mg of 2-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1-H-pyrazolo[3,4-b]pyridin4-ylamino]-butan-1-olasa yellow glass.
Reaction SMILES: C([O:3][C:4](=[O:18])[CH:5]([NH2:17])[CH:6]=[C:7]([CH2:12][P:13]([OH:16])([OH:15])=[O:14])[CH2:8][CH2:9][CH2:10][OH:11])C>O>[NH2:17][CH:5]([CH:6]=[C:7]([CH2:12][P:13]([OH:16])([OH:15])=[O:14])[CH2:8][CH2:9][CH2:10][OH:11])[C:4]([OH:18])=[O:3]
Reactant: CCOC(=O)C(N)C=C(CCCO)CP(=O)(O)O
Solvent: O
Product: NC(C=C(CCCO)CP(=O)(O)O)C(=O)O

Procedure:
1.1 g (3.9 mmol) of 2-amino-7-hydroxy-4-phosphonomethyl-hept-3-enoic acid ethyl ester in 8 ml of water are stirred at 130° C. for 18 hours in a bomb tube. The dark reaction solution is treated with activated carbon and filtered over Hyflo®. The colourless filtrate is concentrated to ~3 ml, and ~25 ml of ethanol are added. The resulting suspension is filtered with suction and dried under a high vacuum at 50° C. 2-amino-7-hydroxy-4-phosphonomethyl-hept-3-enoic acid having a melting point from 190° C. and above (decomp.) is obtained.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([O:8][CH3:9])[CH:5]=[CH:6][CH:7]=1.[Mg].II.[CH2:13]([N:20]1[CH2:25][CH2:24][CH2:23][C:22](=O)[CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[NH4+].[Cl-]>C(OCC)C.C(OC(=O)C)C>[CH3:9][O:8][C:4]1[CH:3]=[C:2]([CH:22]2[CH2:23][CH2:24][CH2:25][N:20]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:21]2)[CH:7]=[CH:6][CH:5]=1
Reactant: COc1cccc(Br)c1
Reactant: O=C1CCCN(Cc2ccccc2)C1
Agent: II
Agent: [Cl-]
Agent: [Mg]
Solvent: CCOC(C)=O
Solvent: CCOCC
Product: COc1cccc(C2CCCN(Cc3ccccc3)C2)c1
Reaction time: 1 h

Procedure:
3-Bromoanisole (14.824 g, 79.26 mmol) was dissolved in 160 mL of diethyl ether dried on Na. Approximately 10% of the solution of 3-bromoanisole in dry diethyl ether was added to magnesium (1.927 g, 79.27 mmol) and a few iodine crystals in a dried 500 mL three-necked flask in a nitrogen atmosphere while stirring. Almost instantly, H2 gas was visible. The brown mixture turned colourless. The remaining solution of 3-bromoanisole in dry diethyl ether was added drop wise. Gas forming was noticed during and after this. After 1 h, a lot of white precipitate was noticed. 1-Benzyl-3-piperidone (5.000 g, 26.42 mmol) was dissolved in 120 mL of dry diethyl ether and added to the reaction mixture drop wise at 30° C. The fine white/yellow precipitate turned more coarse and brownish. Stirring was continued at room temperature for 1 h. Then the suspension was poured in a Erlenmeyer flask and 150 mL of saturated NH4Cl solution was added. About 50 mL of ethylacetate was added to wash out the three-necked flask. The suspension was stirred for 5 min. The organic layer was separated and the aqueous layer was extracted three times with diethyl ether. The organic layers were collected, washed with brine and dried on NaSO4 overnight. The solution was filtered and the solvent evaporated. The residue (about 12.000 g) was extracted with ether once, the solvent evaporated. Yield: 7.6 g (32%). GCMS (EI): m/z 297 (M+), 206 (M−91), 177, 147, 134; GC (100-320° C., 15° C./min): 9.1 min.
Reaction SMILES: N1C=CC=CC=1.[C:7](Cl)(=[O:11])[CH:8]([CH3:10])[CH3:9].[NH2:13][C:14]1[C:22]2[C:17](=[N:18][CH:19]=[C:20]([Cl:38])[C:21]=2[N:23]2[CH2:28][CH2:27][CH2:26][C@@H:25]([N:29]([CH3:37])[C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:24]2)[NH:16][CH:15]=1.[Li+].[OH-]>CN1C(=O)CCC1.CC#N.O.C(Cl)Cl.O>[Cl:38][C:20]1[C:21]([N:23]2[CH2:28][CH2:27][CH2:26][C@@H:25]([N:29]([CH3:37])[C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:34])[CH3:35])[CH2:24]2)=[C:22]2[C:14]([NH:13][C:7](=[O:11])[CH:8]([CH3:10])[CH3:9])=[CH:15][NH:16][C:17]2=[N:18][CH:19]=1
Reactant: CN(C(=O)OC(C)(C)C)[C@@H]1CCCN(c2c(Cl)cnc3[nH]cc(N)c23)C1
Reactant: CC(C)C(=O)Cl
Agent: [Li+]
Agent: [OH-]
Solvent: CC#N
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(C)C(=O)Nc1c[nH]c2ncc(Cl)c(N3CCC[C@@H](N(C)C(=O)OC(C)(C)C)C3)c12
Temperature: 25 °C
Reaction time: 1 h
Yield: 50.6 %

Procedure:
Pyridine (1 mL) and isobutyryl chloride (0.421 g, 3.95 mmol) were added to (R)-tert-butyl 1-(3-amino-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-yl(methyl)carbamate (0.300 g, 0.790 mmol; Example 112, Step A) in NMP (2 mL), and the reaction was stirred at room temperature for 1 hour. 3M aqueous LiOH (3 mL) was then added, and the reaction was stirred for 10 minutes. Water (10 mL) and DCM (10 mL) were then added, and the organic layer was separated, dried, filtered and concentrated. The crude residue was purified by reverse phase chromatography (Biotage SP4, C-18 12M+, 5-95% CH3CN/water) to give (R)-tert-butyl 1-(5-chloro-3-isobutyramido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-yl(methyl)carbamate (0.180 g, 51% yield).
Reaction SMILES: C(C1N=C(N2CCC(F)(F)C2)C2N=NN(CC)C=2N=1)(C)(C)C.[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:40][C:39]([F:42])([F:41])[C:38]([F:44])([F:43])[CH2:37]2)[C:30]2[N:35]=[N:34][NH:33][C:31]=2[N:32]=1)([CH3:26])([CH3:25])[CH3:24].Br[CH2:46][C:47]1[C:51]([CH3:52])=[N:50][O:49][N:48]=1>>[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:40][C:39]([F:41])([F:42])[C:38]([F:43])([F:44])[CH2:37]2)[C:30]2[N:35]=[N:34][N:33]([CH2:46][C:47]3[C:51]([CH3:52])=[N:50][O:49][N:48]=3)[C:31]=2[N:32]=1)([CH3:26])([CH3:24])[CH3:25]
Reactant: CC(C)(C)c1nc(N2CC(F)(F)C(F)(F)C2)c2nn[nH]c2n1
Reactant: Cc1nonc1CBr
Agent: CCn1nnc2c(N3CCC(F)(F)C3)nc(C(C)(C)C)nc21
Product: Cc1nonc1Cn1nnc2c(N3CC(F)(F)C(F)(F)C3)nc(C(C)(C)C)nc21

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-7-(3,3-difluoropyrrolidin-1-yl)-3-ethyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 61), the title compound was prepared from 5-tert-Butyl-7-(3,3,4,4-tetrafluoro-pyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 3-(bromomethyl)-4-methyl-1,2,5-oxadiazole and isolated as light-yellow gum. MS(m/e): 415.3 (MH+).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:14][CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][C@H:9]2[CH2:22][NH:23][C:24](=[O:30])[CH2:25][O:26][CH:27]([CH3:29])[CH3:28])=[CH:4][C:3]=1[F:31].C(OCC)(=O)C.Cl>>[ClH:1].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:14][CH2:13][CH2:12][NH:11][CH2:10][C@H:9]2[CH2:22][NH:23][C:24](=[O:30])[CH2:25][O:26][CH:27]([CH3:28])[CH3:29])=[CH:4][C:3]=1[F:31]
Reactant: CC(C)OCC(=O)NC[C@@H]1CN(C(=O)OC(C)(C)C)CCO[C@H]1c1ccc(Cl)c(F)c1
Agent: Cl
Solvent: CCOC(C)=O
Product: CC(C)OCC(=O)NC[C@@H]1CNCCO[C@H]1c1ccc(Cl)c(F)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 92.8 %

Procedure:
To tert-butyl (6R,7R)-7-(4-chloro-3-fluorophenyl)-6-({[(1-methylethoxy)acetyl]amino}methyl)-1,4-oxazepane-4-carboxylate (384 mg) was added 4.0 M hydrogen chloride-ethyl acetate solution (6.28 ml), and the mixture was stirred at room temperature for 1 hr. The residue obtained by concentration under reduced pressure was crystallized from ethanol-hexane solvent to give the title compound (153.4 mg).
Reaction SMILES: [I:1][C:2]1[NH:6][C:5]([CH:7]([CH3:9])C)=[N:4][C:3]=1[CH3:10].[O:11]1CC[CH2:13][CH:12]1C=O>>[I:1][C:2]1[NH:6][C:5]([CH:7]2[CH2:9][CH2:13][CH2:12][O:11]2)=[N:4][C:3]=1[CH3:10]
Reactant: Cc1nc(C(C)C)[nH]c1I
Reactant: O=CC1CCCO1
Product: Cc1nc(C2CCCO2)[nH]c1I

Procedure:
The title compound was prepared using standard chemical manipulations and procedures similar to those used for the preparation of compound 159.2, except tetrahydrofuran-2-carbaldehyde was used in place of isobutyraldehyde. m/z (ES+) 279 (M+H)+.
Reaction SMILES: Br[C:2]1[C:3]([C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)=[N:4][N:5]([C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][N:8]=2)[CH:6]=1.[CH2:21]([O:28]/[N:29]=[C:30]1\[CH2:31][CH2:32][C:33]2[C:38]\1=[CH:37][CH:36]=[C:35](B(O)O)[CH:34]=2)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O>[CH2:21]([O:28]/[N:29]=[C:30]1\[CH2:31][CH2:32][C:33]2[C:38]\1=[CH:37][CH:36]=[C:35]([C:2]1[C:3]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)=[N:4][N:5]([C:7]3[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][N:8]=3)[CH:6]=1)[CH:34]=2)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: OB(O)c1ccc2c(c1)CC/C2=N\OCc1ccccc1
Reactant: N#Cc1ccc(-n2cc(Br)c(-c3ccncc3)n2)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: N#Cc1ccc(-n2cc(-c3ccc4c(c3)CC/C4=N\OCc3ccccc3)c(-c3ccncc3)n2)nc1
Temperature: 80 °C
Yield: 39 %

Procedure:
To 6-(4-bromo-3-(pyridin-4-yl)-1H-pyrazol-1-yl)nicotinonitrile (0.26 g; Example 6, step 1) in 16 mL acetonitrile and 4 mL water was added (E)-1-(benzyloxyimino)-2,3-dihydro-1H-inden-5-ylboronic acid (0.34 g; Example 2, Step 4) and 0.33 g potassium carbonate. The reaction mixture was purged with nitrogen and 46 mg tetrakis(triphenyphosphine)palladium(0) catalyst was added. The reaction mixture was heated to 80° C. for 1.5 hours, filtered through celite, the filter cake was washed with acetonitrile. The filtrate was evaporated to yield crude product, which was purified by chromatography, eluting with a 10:1 mixture of dichloromethane-methanol to afford 0.15 g (36% yield) product as a pale yellow solid. 1H NMR (CDCl3) was consistent with the desired structure. LC/MS showed one peak with a M+1 molecular ion of m/z 483.2 by positive ESI.
Reaction SMILES: [N:1]1([CH:7]=[CH:8][C:9]([O:11][CH3:12])=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.N1C=CC=CC=1.[F:19][CH:20]([F:24])[C:21](F)=[O:22]>C1(C)C=CC=CC=1>[F:19][CH:20]([F:24])[C:21](=[O:22])[C:8](=[CH:7][N:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[C:9]([O:11][CH3:12])=[O:10]
Reactant: COC(=O)C=CN1CCCCC1
Reactant: O=C(F)C(F)F
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: COC(=O)C(=CN1CCCCC1)C(=O)C(F)F
Temperature: -30 °C
Reaction time: 3 h
Yield: 93.2 %

Procedure:
Methyl 3-piperidin-1-ylacrylate (99%, 8.7 g, 51 mmol) and pyridine (4.26 g, 54 mmol) was initially charged in toluene (150 ml) and cooled to −30° C. At this temperature, difluoroacetyl fluoride (10 g, 61 mmol) was introduced. The reaction mixture was stirred at −30° C. for 3 h and then, over a period of 1 hour, warmed to room temperature. The reaction mixture was washed with deionized water (200 ml). After separation of the phases, the aqueous phase was extracted once with toluene (100 ml). The toluene phases were combined and washed with an aqueous saturated NaCl solution (100 ml), and the solvent was then removed under reduced pressure. This gave methyl 4,4-difluoro-3-oxo-2-(1-piperidin-1-ylmethylidene)butyrate as an orange oil (amount: 12.0 g; purity according to GC: 97.7%; yield: 93.2%).
Reaction SMILES: [N:1]1[C:6]2[C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=3[Se:9][C:5]=2[C:4](=[O:14])[NH:3][N:2]=1.[C:15](=O)([O-])[O-].[K+].[K+].IC>CC(C)=O>[CH3:15][N:3]1[C:4](=[O:14])[C:5]2[Se:9][C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[C:6]=2[N:1]=[N:2]1
Reactant: O=c1[nH]nnc2c1[se]c1ccccc12
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CC(C)=O
Product: Cn1nnc2c([se]c3ccccc32)c1=O
Temperature: 25 °C
Reaction time: 16 h
Yield: 56.8 %

Procedure:
To a solution of 3H-benzo[b]1,2,3-triazino[4,5-d]selenophen-4-one (200 mg, 0.8 mmol) in acetone (50 mL) was added sequentially potassium carbonate (400 mg, 1.6 mmol), iodomethane (0.1 mL, 0.9 mmol) and a catalytic amount of PEG-400 was added at rt and the mixture was stirred at rt for 16 h. The solution was filtered and the solids were washed with acetone. Acetone was evaporated under reduced pressure and the residue was chromatographed over silica gel column using hexane-chloroform (70:30) as eluents to give the product as a off-white solid (120 mg, 47%), mp 190-192° C. IR (neat) νmax 3431, 1673, 1220, 1021 cm−1; 1H NMR (400 MHz, CDCl3): δ 8.56-8.58 (1H, m, H-9), 7.98-8.01 (1H, m, H-6), 7.58-7.66 (2H, m, H-7,8), 4.13 (3H, s, —NCH3); 13C NMR (100 MHz, CDCl3): δ 155.5, 152.8, 142.3, 135.3, 130.4, 129.8, 126.4, 126.2, 126.0, 37.8; LC-MS (positive ion mode): m/z 286, 288 (M+Na)+.
Reaction SMILES: Cl[CH2:2][CH2:3][O:4][C:5]1[CH:13]=[C:12]2[C:8]([C:9]([C:15]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:18]4=[N:19][CH:20]=[CH:21][CH:22]=[C:17]4[CH:16]=3)=[CH:10][N:11]2[CH3:14])=[CH:7][C:6]=1[O:34][CH3:35].[I-:36].[Na+].C1CCCCC1.C(OCC)(=O)C>C(C(C)=O)C>[I:36][CH2:2][CH2:3][O:4][C:5]1[CH:13]=[C:12]2[C:8]([C:9]([C:15]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:18]4=[N:19][CH:20]=[CH:21][CH:22]=[C:17]4[CH:16]=3)=[CH:10][N:11]2[CH3:14])=[CH:7][C:6]=1[O:34][CH3:35]
Reactant: [I-]
Reactant: COc1cc2c(-c3cc4cccnc4n3S(=O)(=O)c3ccc(C)cc3)cn(C)c2cc1OCCCl
Agent: [Na+]
Solvent: C1CCCCC1
Solvent: CCOC(C)=O
Solvent: CCC(C)=O
Product: COc1cc2c(-c3cc4cccnc4n3S(=O)(=O)c3ccc(C)cc3)cn(C)c2cc1OCCI
Yield: 89.3 %

Procedure:
A solution of 2-[6-(2-chloroethoxy)-5-methoxy-1-methyl-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine (0.660 g, 1,294 μmol) in methyl ethyl ketone (10 ml) is placed in a 50 ml single-necked flask and sodium iodide (0.29 g; 1.941 mmol) is then added. The reaction mixture is refluxed for 16 hours. Analysis by thin layer chromatography (50/50 cyclohexane/ethyl acetate) shows that the reaction has come to an end. After returning to 20° C., the reaction mixture is evaporated under reduced pressure and the residue is taken up in a mixture of water (50 ml) and dichloromethane (50 ml), which is separated by settling out; the organic extract is washed with water (30 ml) and dried over magnesium sulfate. After evaporation, the compound obtained is purified by chromatography on silica gel (cartridge FC-10-Si-BP-Sup, 10 g of silica with a particle size of 15-35 μm, elution being carried out with a 70/30 mixture of cyclohexane/ethyl acetate). The fractions containing the expected compound are combined and then evaporated under reduced pressure, giving 2-[6-(2-iodoethoxy)-5-methoxy-1-methyl-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine (0.695 g; 89%) the characteristics of which are as follows:
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:15]([OH:17])=O)=[N:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[CH:6][CH:7]=1.[NH2:18][C:19]1[CH:43]=[CH:42][C:22]2[CH2:23][CH2:24][C:25]3[C:26]([C:39]([NH2:41])=[O:40])=[N:27][N:28]([C:30]4[CH:38]=[CH:37][C:33]5[O:34][CH2:35][O:36][C:32]=5[CH:31]=4)[C:29]=3[C:21]=2[CH:20]=1>>[O:34]1[C:33]2[CH:37]=[CH:38][C:30]([N:28]3[C:29]4[C:21]5[CH:20]=[C:19]([NH:18][C:15]([C:3]6[C:2]([Cl:1])=[CH:7][CH:6]=[C:5]([N:8]7[CH2:9][CH2:10][N:11]([CH3:14])[CH2:12][CH2:13]7)[N:4]=6)=[O:17])[CH:43]=[CH:42][C:22]=5[CH2:23][CH2:24][C:25]=4[C:26]([C:39]([NH2:41])=[O:40])=[N:27]3)=[CH:31][C:32]=2[O:36][CH2:35]1
Reactant: CN1CCN(c2ccc(Cl)c(C(=O)O)n2)CC1
Reactant: NC(=O)c1nn(-c2ccc3c(c2)OCO3)c2c1CCc1ccc(N)cc1-2
Product: CN1CCN(c2ccc(Cl)c(C(=O)Nc3ccc4c(c3)-c3c(c(C(N)=O)nn3-c3ccc5c(c3)OCO5)CC4)n2)CC1

Procedure:
The title compound was synthesized from 0.30 g of 3-chloro-6-(4-methylpiperazin-1-yl)-2-pyridine carboxylic acid, obtained by acidification of its K-salt from step 1, and the title compound of step 4 of Example 161 (0.217 g) by the same procedure used for Example 260. The title compound is a brown solid (0.23 g, 61%), m.p. 264-266° C. (decomposition). Its structure was confirmed by 1H NMR and LC/MS: 1H NMR (d6-DMSO): δ 2.70 (s, 3H), 2.72-4.30 (m, 12H), 6.02 (s, 2H), 6.92-7.12 (m, 4H), 7.22-7.36 (m, 3H), 7.42-7.53 (m, 2H), 7.77 (d, 1H, J=9 Hz), 10.32 (s, 1H). ESI mass spectrum for C30H29ClN7O4+: 586 (M+1).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH2:14][CH2:15][CH3:16])[CH2:10][C:11]([OH:13])=O)=[CH:5][C:4]=1[C:17]([F:20])([F:19])[F:18])#[N:2].[CH2:21]([NH2:24])[CH2:22][CH3:23]>>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH2:14][CH2:15][CH3:16])[CH2:10][C:11]([NH:24][CH2:21][CH2:22][CH3:23])=[O:13])=[CH:5][C:4]=1[C:17]([F:20])([F:19])[F:18])#[N:2]
Reactant: CCCN
Reactant: CCCN(CC(=O)O)c1ccc(C#N)c(C(F)(F)F)c1
Product: CCCNC(=O)CN(CCC)c1ccc(C#N)c(C(F)(F)F)c1

Procedure:
Synthesized as described in example 3 using N-[4-cyano-3-(trifluoromethyl)phenyl]-N-propylglycine and propylamine: 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J=8.6 Hz, 1H), 6.92 (d, J=2.5 Hz, 1H), 6.76 (dd, J=8.8, 2.5 Hz, 1H), 5.94 (bs, 1H), 3.98 (s, 2H), 3.41 (t, J=7.9 Hz, 2H), 3.22 (q, J=6.8 Hz, 2H), 1.68 (m, 2H), 1.45 (m, 2H), 0.99 (t, J=7.3 Hz, 3H), 0.82 (t, J=7.5 Hz, 3H).
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]1[N:15]=[CH:14][C:13]2[N:16]=[CH:17][N:18]([C:19]3[S:23][C:22]([C:24]([O:26][CH3:27])=[O:25])=[C:21]([OH:28])[CH:20]=3)[C:12]=2[CH:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[F:29][C:30]([F:41])([F:40])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[C@H:37](O)[CH3:38].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>ClCCl>[Si:1]([O:8][CH2:9][C:10]1[N:15]=[CH:14][C:13]2[N:16]=[CH:17][N:18]([C:19]3[S:23][C:22]([C:24]([O:26][CH3:27])=[O:25])=[C:21]([O:28][C@H:37]([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=4[C:30]([F:29])([F:40])[F:41])[CH3:38])[CH:20]=3)[C:12]=2[CH:11]=1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]
Reactant: COC(=O)c1sc(-n2cnc3cnc(CO[Si](C)(C)C(C)(C)C)cc32)cc1O
Reactant: C[C@@H](O)c1ccccc1C(F)(F)F
Agent: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COC(=O)c1sc(-n2cnc3cnc(CO[Si](C)(C)C(C)(C)C)cc32)cc1O[C@@H](C)c1ccccc1C(F)(F)F

Procedure:
In a similar manner as described for example B31, 441 mg of methyl 5-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-hydroxythiophene-2-carboxylate, 300 mg of (1R)-1-[2-(trifluoromethyl)phenyl]ethanol, 672 mg of triphenylphosphine (polymer bound, ˜3 mmol/g) and 484 mg of di-tert-butyl azodicarboxylate in 12 ml anhydrous dichloromethane yield the title compound.
Reaction SMILES: [C:1]1([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:6]=[CH:5][C:4]([C:7]([N:9]2[CH2:13][C:12](=O)[CH2:11][C@H:10]2[CH2:15][C:16]([OH:18])=[O:17])=[O:8])=[CH:3][CH:2]=1.[CH3:25][O:26][NH3+:27].[Cl-].C(N(CC)CC)C>C(Cl)(Cl)Cl>[C:1]1([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:2]=[CH:3][C:4]([C:7]([N:9]2[CH2:13][C:12](=[N:27][O:26][CH3:25])[CH2:11][C@H:10]2[CH2:15][C:16]([OH:18])=[O:17])=[O:8])=[CH:5][CH:6]=1
Reactant: O=C(O)C[C@@H]1CC(=O)CN1C(=O)c1ccc(-c2ccccc2)cc1
Reactant: CO[NH3+]
Agent: [Cl-]
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CON=C1C[C@@H](CC(=O)O)N(C(=O)c2ccc(-c3ccccc3)cc2)C1
Yield: 48.7 %

Procedure:
A solution of [(2S)-1-(biphenyl-4-ylcarbonyl)-4-oxopyrrolidin-2-yl]acetic acid (Intermediate 5, 1.50 g, 6.64 mmol), hydroxylamine methyl ether hydrochloride (0.58 g, 6.96 mmol) and triethylamine (1.62 ml, 11.60 mmol) in chloroforme (30 ml) was stirred at RT for 2 days Solvent was removed under reduced pressure and the residue was taken up in ethyl acetate. Organic phase was washed twice with a solution of citric acid 10% and once with brine. Organic phase was then dried on MgSO4, filtered, and concentrated to give [(2S,4EZ)-1-(biphenyl-4-ylcarbonyl)-4-(methoxyimino)pyrrolidin-2-yl]acetic acid as a cream solid (1.14 g). Yield: 45%. HLPC purity: 92%
Reaction SMILES: COC1C=C(C(C2C=CC(OC)=C(OC)C=2)=CC(OC)=O)C=CC=1OC.[CH3:27][O:28][C:29]1[CH:30]=[C:31]([CH:46]=[CH:47][C:48]=1[O:49][CH3:50])[C:32]([C:34]1[CH:39]=[CH:38][C:37]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[CH:36][CH:35]=1)=O.C(OP([CH2:59][C:60]#[N:61])(=O)OCC)C.C[Si](C)(C)[N-][Si](C)(C)C.[Li+]>>[C:37]1([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:38]=[CH:39][C:34]([C:32]([C:31]2[CH:46]=[CH:47][C:48]([O:49][CH3:50])=[C:29]([O:28][CH3:27])[CH:30]=2)=[CH:59][C:60]#[N:61])=[CH:35][CH:36]=1
Reactant: COc1ccc(C(=O)c2ccc(-c3ccccc3)cc2)cc1OC
Reactant: CCOP(=O)(CC#N)OCC
Agent: COC(=O)C=C(c1ccc(OC)c(OC)c1)c1ccc(OC)c(OC)c1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Product: COc1ccc(C(=CC#N)c2ccc(-c3ccccc3)cc2)cc1OC

Procedure:
3-(4-Biphenylyl)-3-(3,4-dimethoxyphenyl)acrylonitrile was prepared analogously to methyl 3,3-bis-(3',4'-dimethoxyphenyl)acrylate using 3,4-dimethoxy-4'-phenylbenzophenone (2.33 g, 7.32 mmol), diethylcyanomethylphosphonate (1.5 mL, 8.1 mmol) and lithium hexamethyldisilazide (8.1 mL, 8.1 mmol, 1M) with a reaction time of 22 hours. The crude product was purified by chromatography (silica gel, 1% ethyl acetate/methylene chloride) to afford 1.76 g (70%) of a mixture of the E and Z isomers as a white solid: mp 132.0-134° C.; 1H NMR (CDCl3) δ 7.70-7.39 (m, 18 H), 7.10-6.80 (m, 6 H), 5.69 (s, 1 H), 5.68 (s, 1 H), 3.95 (s, 6 H), 3.93 (s, 3 H), 3.89 (s, 3 H), 3.85 (s, 3 H); 13C NMR (CDCl3) δ 162.2, 151.1, 148.8, 148.6, 143.0, 142.6, 140.0, 137.9, 135.9, 131.4, 130.1, 129.3, 129.1, 128.8, 128.8, 127.9, 127.1, 127.0, 126.0, 126.9, 123.1, 122.2, 118.3, 118.2, 112.6, 111.1, 110.7, 93.2, 92.9, 56.0, 55.9, 55.8; Anal. Calcd for C23H19NO2. Theoretical: C, 80.92; H, 5.61; N, 4.10. Found: C, 80.55; H, 5.80; N, 3.95.