Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[OH:9].[H-].[Na+].[Cl:12][C:13]1[CH:18]=[C:17]([N+]([O-])=O)[CH:16]=[CH:15][N:14]=1>>[Cl:12][C:13]1[CH:18]=[C:17]([O:9][C:3]2[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=2[Cl:8])[CH:16]=[CH:15][N:14]=1
Reactant: Oc1c(Cl)cccc1Cl
Reactant: O=[N+]([O-])c1ccnc(Cl)c1
Agent: [H-]
Agent: [Na+]
Product: Clc1cc(Oc2c(Cl)cccc2Cl)ccn1
Yield: 64.5 %

Procedure:
Using the method of Example 3, Step A, 2,6-dichlorophenol (2.06 g, 12.6 mmol), 60% sodium hydride in mineral oil (505 mg, 12.6 mmol), and 2-chloro-4-nitropyridine (2.00 g, 12.6 mmol) were reacted at 80° C. overnight to provide 2-chloro-4-(2,6-dichlorophenoxy)pyridine (2.23 g, 64% yield) as an oil. 1H NMR (CDCl3) δ 8.27 (d, 1H), 7.44 (d, 2H), 7.24 (t, 1H), 6.71-6.75 (m, 2H).
Reaction SMILES: FC(F)(F)C(O)=O.[CH:8]1([CH:13]([N:18]2[CH:22]=[C:21]([C:23]3[C:24]4[CH:32]=[CH:31][N:30](OCC[Si](C)(C)C)[C:25]=4[N:26]=[C:27](C)[N:28]=3)[CH:20]=[N:19]2)[CH2:14][CH:15]2[CH2:17][CH2:16]2)[CH2:12][CH2:11][CH2:10][CH2:9]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:8]1([CH:13]([N:18]2[CH:22]=[C:21]([C:23]3[C:24]4[CH:32]=[CH:31][NH:30][C:25]=4[N:26]=[CH:27][N:28]=3)[CH:20]=[N:19]2)[CH2:14][CH:15]2[CH2:17][CH2:16]2)[CH2:12][CH2:11][CH2:10][CH2:9]1
Reactant: Cc1nc(-c2cnn(C(CC3CC3)C3CCCC3)c2)c2ccn(OCC[Si](C)(C)C)c2n1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: c1nc(-c2cnn(C(CC3CC3)C3CCCC3)c2)c2cc[nH]c2n1
Reaction time: 1 h
Yield: 0.1 %

Procedure:
4-[1-(1-Cyclopentyl-2-cyclopropylethyl)-1H-pyrazol-4-yl]-7-[2-(trimethylsilyl)ethoxy]-methyl-7H-pyrrolo[2,3-d]pyrimidine trifluoroacetate salt (13 mg, 0.023 mol) was stirred at room temperature in a solution of DCM (2 mL) containing TFA (1.5 mL) for two hours. The solvent was removed in vacuo. The resulting residue was redissolved in THF (3 mL), and 6N NaOH (2 mL) was added. After stirring for one hour, the mixture was partitioned between water and ethyl acetate. The organic layer was dried over sodium sulfate and the solvent was removed in vacuo. Purification via preparative-HPLC/MS (C18 eluting with a gradient of H2O and ACN containing 0.1% TFA) afforded the product (9 mg, 90%).
Reaction SMILES: CN1CCOCC1.[CH3:8][C:9]([CH3:25])([O:11][C:12]([NH:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[C:16]=1[C:17]([OH:19])=O)=[O:13])[CH3:10].[NH2:26][C:27]1[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=1.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH3:33][C:30]1[CH:31]=[CH:32][C:27]([NH:26][C:17](=[O:19])[C:16]2[C:20]([CH3:24])=[CH:21][CH:22]=[CH:23][C:15]=2[NH:14][C:12]([O:11][C:9]([CH3:8])([CH3:10])[CH3:25])=[O:13])=[CH:28][CH:29]=1
Reactant: Cc1cccc(NC(=O)OC(C)(C)C)c1C(=O)O
Reactant: Cc1ccc(N)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: Cc1ccc(NC(=O)c2c(C)cccc2NC(=O)OC(C)(C)C)cc1
Temperature: 18 °C
Reaction time: 16 h

Procedure:
Firstly N-methylmorpholine (6.15 mL. 5.64 g, 55.8 mmol) and then O-(benzotriazol-1-yl N,N,N′N′-tetramethyluronium hexalfuorophosphate (10.15 g, 26.8 mmol) are added to a stirred mixture of 2-{([(1,1-dimethylethoxy)carbonyl]amino}-6-methylbenzoic acid (5.60 g, 22.3 mmol) and p-toluidine 4.78 g, 44.6 mmol) in dry dimethylformamide (110 mL) under an argon atmosphere, and stirred at 18° C. for 16 hours. The solvent is evaporated off under reduced pressure to give a residue which is treated with aqueous sodium hydrogen carbonate solution (200 mL of 10%) and extracted with dichloromethane (3×100 mL). The combined extracts are washed with aqueous citric acid solution (100 mL of 10%), dried (Na2SO4), filtered and the solvent is evaporated off under reduced pressure to yield the crude product which is purified by column chromatography on silica gel, eluent 20% ethyl acetate in hexane, and recrystallised from tert-butyl methyl ether-hexane to give the title compound as a colourless crystalline solid, m.p. 250° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[C:13]([F:15])[C:12]([N+:16]([O-])=O)=[CH:11][C:10]=2[CH3:19])[CH:5]=[CH:4][N:3]=1>C(O)C.[Ni]>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:10]([CH3:19])=[CH:11][C:12]([NH2:16])=[C:13]([F:15])[CH:14]=2)[CH:5]=[CH:4][N:3]=1
Reactant: Cc1cc([N+](=O)[O-])c(F)cc1Oc1ccnc(Cl)c1
Agent: [Ni]
Solvent: CCO
Product: Cc1cc(N)c(F)cc1Oc1ccnc(Cl)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
To a solution of 2-chloro-4-(5-fluoro-2-methyl-4-nitrophenoxy)pyridine (0.48 g, 1.698 mmol) in ethanol (20 mL) was added Raney Ni (0.4 g). The mixture was stirred under a hydrogen atmosphere (1 atm) overnight at RT. The reaction mixture was filtered through a pad of Celite® and the filtrate was concentrated to obtain the crude 4-(2-chloropyridin-4-yloxy)-2-fluoro-5-methylbenzenamine (assuming a 100% yield).
Reaction SMILES: [CH2:1]([NH2:9])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:11]1[C:12]2[C:24]([Cl:25])=[C:23]([CH3:26])[S:22][C:13]=2[N:14]=[C:15]([C:17]2[O:21][N:20]=[CH:19][CH:18]=2)[N:16]=1>>[O:21]1[C:17]([C:15]2[N:16]=[C:11]([NH:9][CH2:1][CH2:2][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)[C:12]3[C:24]([Cl:25])=[C:23]([CH3:26])[S:22][C:13]=3[N:14]=2)=[CH:18][CH:19]=[N:20]1
Reactant: Cc1sc2nc(-c3ccno3)nc(Cl)c2c1Cl
Reactant: NCCc1ccccc1
Product: Cc1sc2nc(-c3ccno3)nc(NCCc3ccccc3)c2c1Cl

Procedure:
With the procedure of Example 1, the reaction of phenethylamine with 4-chloro-2-(isoxazol-5-yl)-5-chloro-6-methyl-thieno-[2,3-d]-pyrimidine yields 2-(isoxazol-5-yl)-4-phenethylamino-5-chloro-6-methyl-thieno-[2,3-d]-pyrimidine.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[OH:7][C:8]1[CH:12]=[C:11]([CH3:13])[NH:10][N:9]=1.[Cl:14][C:15]1[CH:16]=[C:17]([C:23]([F:26])([F:25])[F:24])[CH:18]=[C:19]([F:22])[C:20]=1F.Cl>CN(C=O)C>[Cl:14][C:15]1[CH:16]=[C:17]([C:23]([F:24])([F:25])[F:26])[CH:18]=[C:19]([F:22])[C:20]=1[O:7][C:8]1[CH:12]=[C:11]([CH3:13])[NH:10][N:9]=1
Reactant: Cc1cc(O)n[nH]1
Reactant: Fc1cc(C(F)(F)F)cc(Cl)c1F
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cc(Oc2c(F)cc(C(F)(F)F)cc2Cl)n[nH]1
Temperature: 70 °C
Yield: 31.1 %

Procedure:
Potassium carbonate (1.66 g, 12 mmol) was added to a solution of 3-hydroxy-5-methylpyrazole (2.45 g, 25.0 mmol) and 3-chloro-4,5-difluorobenzotrifluoride (2.5 g, 25.0 mmol) in DMF (40 ml), and the mixture was stirred under heating at 70° C. for 4 hours. After completion of the reaction, the reaction mixture was poured into 2N hydrochloric acid (100 ml) and extracted with ethyl acetate (50 ml×3). An organic layer was washed with water, dried over anhydrous magnesium sulfate and filtered to remove a desiccant, and the solvent was distilled off from the filtrate under reduced pressure. The resultant crude product was purified with a silica gel column (ethyl acetate/hexane=1/5), to give a white solid of 3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole (2.29 g, yield: 33.8%). mp: 171-174° C.; 1H-NMR (CDCl3, TMS, ppm): δ 2.27 (s, 3H), 5.71 (s, 1H), 7.37 (dd, JHF=1.8 and 9.4 Hz, 1H), 7.54 (s, 1H), 8.85-9.55 (br s, 1H).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([NH:7]C(=O)OCC)[CH:2]=1.[CH3:13][O:14][CH2:15][CH:16]1[CH2:20][O:19][C:18](=O)[O:17]1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>O>[CH3:13][O:14][CH2:15][CH:16]1[O:17][C:18](=[O:19])[N:7]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[CH2:20]1
Reactant: COCC1COC(=O)O1
Reactant: CCOC(=O)Nc1cccnc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Product: COCC1CN(c2cccnc2)C(=O)O1
Yield: 83.6 %

Procedure:
A mixture of 16.8 g of ethyl pyridin-3-yl-carbamate, 20 g of 4-methoxymethyl-1,3-dioxolan-2-one and 2.8 g of potassium carbonate was heated to 160° for 3 h. The mixture was cooled and treated with ethyl acetate and water. The phases were separated, the aqueous phase was extracted with ethyl acetate and the organic phase was washed with saturated sodium chloride solution. The organic phases were combined, dried with magnesium sulfate and concentrated. Chromatography of the residue (21 g) on silica gel with ethyl acetate/methanol mixtures (1:0-20:1) yielded 17.6 g of (RS)-5-methoxymethyl-3-pyridin-3-yl-oxazolidin-2-one which was recrystallized from diethyl ether. M.p.: 65°-66°.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:11]([OH:13])=O)=[CH:4][NH:5][C:6]=1[C:7]([O:9][CH3:10])=[O:8].CC[N:16](C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[NH2:16][C:11]([C:3]1[C:2]([Cl:1])=[C:6]([C:7]([O:9][CH3:10])=[O:8])[NH:5][CH:4]=1)=[O:13]
Reactant: COC(=O)c1[nH]cc(C(=O)O)c1Cl
Reactant: CCN(C(C)C)C(C)C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Product: COC(=O)c1[nH]cc(C(N)=O)c1Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 59 %

Procedure:
To a solution of 4-chloro-5-[(methyloxy)carbonyl]-1H-pyrrole-3-carboxylic acid (0.075 g, 0.368 mmol) in DMF (1 mL) was added DIPEA (0.097 mL, 0.553 mmol) and HATU (0.168 g, 0.442 mmol). Ammonia was bubbled through the reaction mixture for 5 min. and the reaction stirred at RT for 1 h. The crude material was purified by HPLC. The desired fractions were collected and lypholized to afford methyl 4-(aminocarbonyl)-3-chloro-1H-pyrrole-2-carboxylate (0.044 g, 59% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 12.40-12.56 (m, 1H) 7.54 (d, 1H) 7.29 (br. s., 1H) 7.13 (br. s., 1H) 3.80 (s, 3H). MS: m/z 203.0 (M+1).
Reaction SMILES: [C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].[H-].[Na+].C(=O)(O[CH:16]([C:19]1[S:20][CH:21]=[CH:22][CH:23]=1)[CH:17]=[CH2:18])OC.O>C1COCC1.C(Cl)(Cl)Cl>[S:20]1[CH:21]=[CH:22][CH:23]=[C:19]1[CH:16]([CH:2]([C:1]([O:8][CH3:9])=[O:7])[C:3]([O:5][CH3:6])=[O:4])[CH:17]=[CH2:18]
Reactant: C=CC(OC(=O)OC)c1cccs1
Reactant: COC(=O)CC(=O)OC
Agent: [H-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: C1CCOC1
Solvent: O
Product: C=CC(c1cccs1)C(C(=O)OC)C(=O)OC
Temperature: 60 °C

Procedure:
Cycloheptyl ligand IV (10.2 mg, 0.030 mmol) and Mo(CO)3(C2H5CN)3 (6.9 mg, 0.020 mmol) were dissolved in 1.0 ml of THF at rt. The reaction mixture was heated at 60° C. for 1 h. After cooling to rt., 1.0 ml of THF solution of sodium dimethylmalonate enolate, prepared from dimethyl malonate (58.0 mg, 0.44 mmol) and sodium hydride (10.2 mg, 0.40 mmol) in tetrahydrofuran, and methyl 1-(2-thienyl)-2-propenyl carbonate were added successively. The reaction mixture was heated at 65° C. for 4.5 h. The reaction mixture was poured into water and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, and the solvent was removed under reduced pressure. The ratio of dimethyl 2-(1-thiophene-2-yl-allyl)-malonate and linear compound was determined by 1H NMR (400 MHz) to be 16.0/1. The residue was chromatographed on silica (1/7 ethyl acetate/petroleum ether, Rf=0.3) to yield the mixture of branched and linear compound. (40.3 mg, 78%) [α]D−31.1° (c 1.35, CHCl3); 92% e.e. for major isomer.
Reaction SMILES: [C:1]([C:5]1[Se:9][C:8]([C:10]#[N:11])=[C:7]([OH:12])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH:13]S(O)(=O)=O>FC(F)(F)C(O)=O>[C:1]([C:5]1[Se:9][C:8]([C:10]([NH2:11])=[O:13])=[C:7]([OH:12])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: O=S(=O)(O)O
Reactant: CC(C)(C)c1cc(O)c(C#N)[se]1
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(C)c1cc(O)c(C(N)=O)[se]1
Temperature: 0 °C
Reaction time: 6 h
Yield: 86 %

Procedure:
To an ice cold solution of 5-tert-butyl-3-hydroxyselenophene-2-carbonitrile (0.5 g) in trifluoroacetic acid (2 mL) was added H2SO4 (0.5 mL) dropwise for 15 min. The reaction mixture was allowed to rt and stirred for 6 h. The reaction mixture was poured into ice cold water extracted with chloroform (3×50 mL). The combined chloroform layer was washed with water, brine and dried over sodium sulfate. The solution was filtered and evaporated the solvent. The residue was chromatographed over silica gel column using hexane-EtOAc (75:25) as eluents to give the product as a brown color solid (460 mg, 86%), mp 164-168° C. 1H NMR (400 MHz, CDCl3): δ 11.53 (1H, br s), 6.81 (1H, s), 5.35 (2H, s), 1.35 (9H, s); LC-MS (negative ion mode): m/z 244, 246 (M−H)−.
Reaction SMILES: [H-].[Na+].[CH2:3]([C:5]1[NH:6][C:7]2[C:8]([N:15]=1)=[N:9][C:10]([CH3:14])=[CH:11][C:12]=2[CH3:13])[CH3:4].[CH2:16]([O:18][C:19]([C:21]1([C:26]2[S:27][C:28]([CH2:31]Cl)=[CH:29][CH:30]=2)[CH2:25][CH:24]=[CH:23][CH2:22]1)=[O:20])[CH3:17].[Na+].[Cl-]>CN(C=O)C>[CH2:16]([O:18][C:19]([C:21]1([C:26]2[S:27][C:28]([CH2:31][N:15]3[C:8]4=[N:9][C:10]([CH3:14])=[CH:11][C:12]([CH3:13])=[C:7]4[N:6]=[C:5]3[CH2:3][CH3:4])=[CH:29][CH:30]=2)[CH2:25][CH:24]=[CH:23][CH2:22]1)=[O:20])[CH3:17]
Reactant: CCc1nc2nc(C)cc(C)c2[nH]1
Reactant: CCOC(=O)C1(c2ccc(CCl)s2)CC=CC1
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)C1(c2ccc(Cn3c(CC)nc4c(C)cc(C)nc43)s2)CC=CC1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a suspension of petroleum ether washed NaH (1.1 equiv.) in DMF was added 2-ethyl-5,7-dimethylimidazo[4,5-b]pyridine (7) (1.1 equiv.). The reaction mixture was stirred for 15 minutes at ambient temperature and then the product of Step 4, above (5) (1 equiv.), dissolved in DMF, was cannulated into the mixture of the anion in DMF. The reaction mixture was stirred at ambient temperature for 17 hours and was then poured into saturated NaCl solution and extracted 2 times with EtOAc. The combined extracts were dried over MgSO4, filtered and concentrated to dryness. The crude material was chromatographed on silica gel with a gradient elution from 50% EtOAc in hexanes to 60% EtOAc in hexanes to yield the title compound (6).
Reaction SMILES: [CH:1]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[CH:8]2)([CH2:3]C)[CH3:2].C(C1C=C2C(=CC=1)N(C(=O)C(F)(F)F)C=C2)(CC)C>>[CH:1]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[CH:8]2)([CH3:3])[CH3:2]
Reactant: CCC(C)c1ccc2[nH]ccc2c1
Agent: CCC(C)c1ccc2c(ccn2C(=O)C(F)(F)F)c1
Product: CC(C)c1ccc2[nH]ccc2c1

Procedure:
5-Sec-butyl-1H-indole; from 5-sec-butyl-1-trifluoroacetylindole (Example 2c) (94%).
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[CH2:11][CH2:12][C:13]1[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][CH:14]=1.[N+:21]([O-])([O-:23])=[O:22].[K+]>S(=O)(=O)(O)O>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([N+:21]([O-:23])=[O:22])=[CH:8][CH:9]=2)[CH:4]=[C:3]1[CH2:11][CH2:12][C:13]1[CH:14]=[CH:15][C:16]([C:17]#[N:18])=[CH:19][CH:20]=1
Reactant: Cn1c(CCc2ccc(C#N)cc2)cc2ccccc21
Reactant: O=[N+]([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Product: Cn1c(CCc2ccc(C#N)cc2)cc2cc([N+](=O)[O-])ccc21
Temperature: 2 °C
Reaction time: 0.5 h

Procedure:
Within 2 hours 1.7 g (6.53 mmol) of 4-[2-(1-methyl-indol-2-yl)ethyl]benzonitrile is dissolved in 20 ml conc. sulphuric acid at 15° C. and then cooled to 2° C. Then 0.66 g (6.53 mmol) of potassium nitrate are added batchwise (temperature rise to about 10° C.). The mixture is stirred for a further 30 minutes at 2-5° C. and then poured onto ice. The yellowish precipitate formed is filtered off and washed with water.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([C@@H:10]([NH:12][C:13]2[N:18]=[C:17]([N:19]3[C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=4[N:21]=[CH:20]3)[CH:16]=[CH:15][N:14]=2)[CH3:11])[CH:7]=[CH:8][CH:9]=1)(O)=[O:2].[CH2:28]([NH2:34])[C:29]1[O:33][CH:32]=[CH:31][CH:30]=1.Cl.CN(C)CCCN=C=NCC.CN(C1C=CC=CN=1)C>C(Cl)Cl.C(N(CC)CC)C>[O:33]1[CH:32]=[CH:31][CH:30]=[C:29]1[CH2:28][NH:34][C:1]([C:4]1[CH:5]=[C:6]([C@@H:10]([NH:12][C:13]2[N:18]=[C:17]([N:19]3[C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=4[N:21]=[CH:20]3)[CH:16]=[CH:15][N:14]=2)[CH3:11])[CH:7]=[CH:8][CH:9]=1)=[O:2]
Reactant: NCc1ccco1
Reactant: C[C@H](Nc1nccc(-n2cnc3ccccc32)n1)c1cccc(C(=O)O)c1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccccn1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C[C@H](Nc1nccc(-n2cnc3ccccc32)n1)c1cccc(C(=O)NCc2ccco2)c1
Temperature: 25 °C
Yield: 61.8 %

Procedure:
2-[(S)1-(3-carboxyphenyl)ethylamino]-4-[benzimidazol-1-yl]pyrimidine (EXAMPLE 58, 14.2 mg) and furfurylamine (11 μL, 0.12 mmol) were mixed in CH2Cl2 (2 mL) under nitrogen. Triethylamine (28 μL), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (26.3 mg) and dimethylaminopyridine (approx. 1 mg) were added and the mixture stirred at room temperature. After 16 h the mixture was concentrated in vacuo then eluted directly on silica gel (60:40 hexanes:acetone to 50:50 hexanes:acetone) to yield 10.7 mg of the title compound. Mass spectrum (ESI) 439.2 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]([CH2:14][C:15]([OH:17])=O)[CH:7]=[C:6]2[C:18]1[NH:26][C:21]2=[N:22][CH:23]=[CH:24][CH:25]=[C:20]2[CH:19]=1.[CH3:27][N:28]1[CH2:33][CH2:32][NH:31][CH2:30][C:29]1=[O:34]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]([CH2:14][C:15]([N:31]1[CH2:32][CH2:33][N:28]([CH3:27])[C:29](=[O:34])[CH2:30]1)=[O:17])[CH:7]=[C:6]2[C:18]1[NH:26][C:21]2=[N:22][CH:23]=[CH:24][CH:25]=[C:20]2[CH:19]=1
Reactant: COc1cc2c(-c3cc4cccnc4[nH]3)cn(CC(=O)O)c2cc1OC
Reactant: CN1CCNCC1=O
Product: COc1cc2c(-c3cc4cccnc4[nH]3)cn(CC(=O)N3CCN(C)C(=O)C3)c2cc1OC
Yield: 69.1 %

Procedure:
4-{[5,6-Dimethoxy-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-indol-1-yl]acetyl}-1-methylpiperazin-2-one is prepared by following the procedure described in example 93, but using 0.1 g of 2-[5,6-dimethoxy-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)indol-1-yl]acetic acid and 0.039 g of 1-methylpiperazin-2-one. 0.088 g of 4-{[5,6-dimethoxy-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)indol-1-yl]acetyl}-1-methylpiperazin-2-one is obtained, the characteristics of which are as follows:
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:11]=[C:12]([NH:16][C:17]([CH:19]3[CH2:23][CH2:22][C:21](=[O:24])[O:20]3)=[O:18])[CH:13]=[CH:14][CH:15]=2)[CH:5]=[C:4]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[OH:31])[N:3]=1.[OH-:32].[Na+:33]>CO>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:11]=[C:12]([NH:16][C:17](=[O:18])[CH:19]([OH:32])[CH2:23][CH2:22][C:21]([O-:20])=[O:24])[CH:13]=[CH:14][CH:15]=2)[CH:5]=[C:4]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[OH:31])[N:3]=1.[Na+:33]
Reactant: N#Cc1c(-c2cccc(NC(=O)C3CCC(=O)O3)c2)cc(-c2ccccc2O)nc1N
Reactant: [OH-]
Agent: [Na+]
Solvent: CO
Product: N#Cc1c(-c2cccc(NC(=O)C(O)CCC(=O)[O-])c2)cc(-c2ccccc2O)nc1N
Reaction time: 0.17 h
Yield: 60 %

Procedure:
To a suspension of N-{3-[2-amino-3-cyano-6-(2-hydroxyphenyl)-4-pyridinyl]phenyl}-5-oxotetrahydro-2-furancarboxamide (0.250 g, 0.603 mmol) in methanol (10 mL) was added dropwise 2N NaOH solution (0.3 mL). After the mixture was stirred for 10 minutes, insoluble solid was filtered off. The filtrate was concentrated under reduced pressure and the residue was crystallized from methanol and ethyl ether. The resulting solid was collected by filtration under an argon atmosphere, washed with ethyl ether, and dried under reduced pressure to give Sodium 5-({3-[2-amino-3-cyano-6-(2-hydroxyphenyl)-4-pyridinyl]phenyl}amino)-4-hydroxy-5-oxopentanoate as a pale yellow solid (0.165 g, yield 60%).
Reaction SMILES: [NH2:1][CH:2]([C:11]1[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[CH:13][C:12]=1[O:19][CH3:20])[CH2:3][CH2:4][CH2:5][CH2:6][C:7]([O:9]C)=O.[N:21]1([C:27]2[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=2)[CH:30]=O)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1>>[CH3:20][O:19][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([O:17][CH3:18])[C:11]=1[CH:2]1[N:1]([CH2:30][C:29]2[CH:32]=[CH:33][CH:34]=[C:27]([N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:28]=2)[C:7](=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3]1
Reactant: O=Cc1cccc(N2CCCCC2)c1
Reactant: COC(=O)CCCCC(N)c1c(OC)cccc1OC
Product: COc1cccc(OC)c1C1CCCCC(=O)N1Cc1cccc(N2CCCCC2)c1

Procedure:
Prepared according to the described general procedure 1 (GP1) by reaction of methyl 6-amino-6-(2,6-dimethoxyphenyl)hexanoate with commercially available 3-(piperidin-1-yl)benzaldehyde. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions A): tR=0.65 min.; [M+H]+: 423.10 g/mol.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9]([CH2:12][S:13]([CH3:16])(=[O:15])=[O:14])=[CH:8][C:4]=1[C:5]([OH:7])=O.Cl.[CH2:18]([O:20][CH2:21][CH2:22][N:23]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[N:25]=[C:24]1[N:32]1[CH2:38][CH2:37][CH2:36][N:35]([CH2:39][CH2:40][C:41]2([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[CH2:45][CH2:44][NH:43][CH2:42]2)[CH2:34][CH2:33]1)[CH3:19]>>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9]([CH2:12][S:13]([CH3:16])(=[O:15])=[O:14])=[CH:8][C:4]=1[C:5]([N:43]1[CH2:44][CH2:45][C:41]([CH2:40][CH2:39][N:35]2[CH2:36][CH2:37][CH2:38][N:32]([C:24]3[N:23]([CH2:22][CH2:21][O:20][CH2:18][CH3:19])[C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=4[N:25]=3)[CH2:33][CH2:34]2)([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH2:42]1)=[O:7]
Reactant: CCOCCn1c(N2CCCN(CCC3(c4ccccc4)CCNC3)CC2)nc2ccccc21
Reactant: COc1ccc(CS(C)(=O)=O)cc1C(=O)O
Agent: Cl
Product: CCOCCn1c(N2CCCN(CCC3(c4ccccc4)CCN(C(=O)c4cc(CS(C)(=O)=O)ccc4OC)C3)CC2)nc2ccccc21

Procedure:
Prepare by the method of Example 56.1 using 2-methoxy-5-(methylsulfonylmethyl)benzoic acid and 3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine hydrochloric acid salt (prepared from (−)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid salt) to give the title compound.
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]2[C:11](=[O:19])[NH:12][NH:13][C:14]=2[C:15]([F:18])([F:17])[F:16])=[CH:5][CH:4]=1.[CH3:20][C:21]([O:23][CH2:24][C@H:25]1[O:30][C@H:29](Br)[C@H:28]([O:32][C:33]([CH3:35])=[O:34])[C@@H:27]([O:36][C:37]([CH3:39])=[O:38])[C@@H:26]1[O:40][C:41]([CH3:43])=[O:42])=[O:22].C(=O)([O-])[O-].[K+].[K+].O>C(#N)C>[CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]2[C:11]([O:19][C@@H:29]3[O:30][C@H:25]([CH2:24][O:23][C:21](=[O:22])[CH3:20])[C@@H:26]([O:40][C:41](=[O:42])[CH3:43])[C@H:27]([O:36][C:37](=[O:38])[CH3:39])[C@H:28]3[O:32][C:33](=[O:34])[CH3:35])=[N:12][NH:13][C:14]=2[C:15]([F:18])([F:17])[F:16])=[CH:5][CH:4]=1
Reactant: CC(=O)OC[C@H]1O[C@H](Br)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: CSc1ccc(Cc2c(C(F)(F)F)[nH][nH]c2=O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: CSc1ccc(Cc2c(O[C@@H]3O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]3OC(C)=O)n[nH]c2C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 46.6 %

Procedure:
To a solution of 1,2-dihydro-4-[(4-methylthiophenyl)methyl]-5-trifluoromethyl-3H-pyrazol-3-one (2.0 g) in acetonitrile (100 mL) were added acetobromo-α-D-glucose (3.1 g) and potassium carbonate (1.1 g), and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=1/1) to give 4-[(4-methylthiophenyl)methyl]-3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-5-trifluoromethyl-1H-pyrazole (2.0 g).