Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:3]=1[CH2:4][O:5][C:6]1[C:7]([NH:12][C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)=S)=[N:8][CH:9]=[CH:10][CH:11]=1.[NH3:30]>>[Cl:1][C:2]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:3]=1[CH2:4][O:5][C:6]1[C:7]([NH:12][C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)=[NH:30])=[N:8][CH:9]=[CH:10][CH:11]=1
Reactant: N
Reactant: O=[N+]([O-])c1ccc(NC(=S)Nc2ncccc2OCc2c(F)cccc2Cl)cc1
Product: N=C(Nc1ccc([N+](=O)[O-])cc1)Nc1ncccc1OCc1c(F)cccc1Cl
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A mixture of yellow mercuric oxide (1.26g, 0.006 mol), N-[3-(2-chloro-6 fluorobenzyloxy)pyrid-2-yl]-N'-(4-nitrophenyl)thiourea (2.08g, 0.005 mol) and methanolic ammonia solution (40 ml) was stirred for 24 hours at room temperature, then heated under reflux for 30 min. The solvent was removed in vacuo and the black residue was boiled with chloroform and filtered hot. Evaporation of the solvent and recrystallisation from ethanol gave the desired product. Yield 1.16 g (58%), m.p 180°-182 ° C.
Reaction SMILES: I[CH2:2][C@@H:3]([CH3:16])[CH2:4][N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7][C:6]1=[O:15].[CH2:17]([O:20][CH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)[CH2:18][CH3:19]>CC#N>[CH3:16][C@H:3]([CH2:2][N:24]1[CH2:25][CH2:26][CH:21]([O:20][CH2:17][CH2:18][CH3:19])[CH2:22][CH2:23]1)[CH2:4][N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7][C:6]1=[O:15]
Reactant: CCCOC1CCNCC1
Reactant: C[C@H](CI)Cn1c(=O)ccc2ccccc21
Solvent: CC#N
Product: CCCOC1CCN(C[C@@H](C)Cn2c(=O)ccc3ccccc32)CC1
Temperature: 50 °C
Reaction time: 24 h
Yield: 25.6 %

Procedure:
A 4 mL vial was charged with crude (S)-1-(3-iodo-2-methylpropyl)-1H-quinolin-2-one (0.190 g), 4-propyloxypiperidine (0.137 g, 0.96 mmol) and dry CH3CN (2.5 mL). The mixture was shaken at 50° C. for 24 h and then purified by cation-exchange CC followed by flash CC (SiO2; EtOAc/MeOH 1:4) to give the title compound (0.051 g, 17%). 1H NMR (CD3OD) δ 7.85 (d, J=9.6 Hz), 7.70-7.63 (m, 2H), 7.60 (brt, J=7.8 Hz, 1H), 7.26 (brt, 7.6 Hz), 6.63 (d, J=9.6 Hz, 1H), 4.39-4.23 (m, 2H), 3.37 (t, J=6.6 Hz), 3.28-3.18 (m, 1H), 2.77-2.69 (m, 1H), 2.64-2.58 (m, 1H), 2.35 (dd, J=8.4, 12.0 Hz), 2.51-2.21 (m, 1H), 2.18 (dd, J=4.8, 12.0 Hz), 2.13-2.04 (m, 1H), 2.00-1.92 (m, 1H), 1.84-1.75 (m, 2H), 1.58-1.32 (m, 4H), 0.95-0.85 (m, 6H); 13C NMR (CD3OD) δ 163.7, 140.2, 139.5, 130.8, 129.2, 12.5, 121.4, 120.4, 115.2, 75.3, 69.5, 63.6, 52.3, 51.5, 46.8, 31.4, 31.3, 30.0, 23.1, 16.1, 9.8.
Reaction SMILES: [NH2:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11](=[N:13][OH:14])[NH2:12])=[CH:7][CH:6]=1)(=[O:4])=[O:3].C(C1C=CC(S(N)(=O)=O)=CC=1)#N.[CH3:27][CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][N:29]1[C:34]1[CH:42]=[CH:41][C:37]([C:38](O)=O)=[CH:36][C:35]=1[NH:43][S:44]([CH3:47])(=[O:46])=[O:45]>>[CH3:27][CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][N:29]1[C:34]1[CH:42]=[CH:41][C:37]([C:38]2[O:14][N:13]=[C:11]([C:8]3[CH:7]=[CH:6][C:5]([S:2]([NH2:1])(=[O:4])=[O:3])=[CH:10][CH:9]=3)[N:12]=2)=[CH:36][C:35]=1[NH:43][S:44]([CH3:47])(=[O:45])=[O:46]
Reactant: CC1CCCCN1c1ccc(C(=O)O)cc1NS(C)(=O)=O
Reactant: NC(=NO)c1ccc(S(N)(=O)=O)cc1
Agent: N#Cc1ccc(S(N)(=O)=O)cc1
Product: CC1CCCCN1c1ccc(-c2nc(-c3ccc(S(N)(=O)=O)cc3)no2)cc1NS(C)(=O)=O

Procedure:
The title compound was prepared following procedure described for example 4, step 1, but starting from 4-(aminosulfonyl)-N′-hydroxybenzenecarboximidamide, prepared as described in WO 2006/013104 A1 from 4-cyanobenzene-1-sulfonamide (ABCR; CD10716), (322.85 mg; 1.50 mmol) and Intermediate 25 (562.30 mg; 1.80 mmol). The reaction mixture was evaporated under reduce pressure and was purified by flash chromatography (c-hex/EtOAc: 9.5/0.5), affording the title compound as a pale yellow solid. 1H NMR (DMSO-d6, 300 MHz) δ 8.68 (br s, 1H), 8.31-8.27 (m, 2H), 8.22 (d, J=2.0 Hz, 1H), 8.06-8.03 (m, 2H), 7.94 (dd, J=8.2, 1.8 Hz, 1H), 7.57 (br s, 2H), 7.55 (s, 1H), 3.23 (s, 3H), 3.20-3.13 (m, 1H), 2.94-2.87 (m, 1H), 2.66-2.57 (m, 1H), 1.84-1.66 (m, 4H), 1.50-1.44 (m, 2H), 0.82 (d, J=6.1 Hz, 3H). LC/MS (Method B): 490.4 (M−H)−, 492.4 (M+H)+. HPLC (Method A) Rt 4.34 min (Purity: 97.9%).
Reaction SMILES: C([C@@:5]1([OH:26])[C@H:9]([O:10]CCCC)[C@@H:8]([C:15](=[SnH2])[OH:16])[O:7][C@H:6]1[N:18]1[CH:25]=[CH:24][C:22](=[O:23])[NH:21][C:19]1=[O:20])CCC.Br[CH2:28][CH2:29][CH2:30][CH2:31][CH3:32].[I-].[Na+]>CN(C=O)C>[CH2:28]([O:26][C@@H:5]1[C@H:9]([OH:10])[C@@H:8]([CH2:15][OH:16])[O:7][C@H:6]1[N:18]1[CH:25]=[CH:24][C:22](=[O:23])[NH:21][C:19]1=[O:20])[CH2:29][CH2:30][CH2:31][CH3:32]
Reactant: CCCCO[C@@H]1[C@@H](C(O)=[SnH2])O[C@@H](n2ccc(=O)[nH]c2=O)[C@@]1(O)CCCC
Reactant: CCCCCBr
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCCO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1n1ccc(=O)[nH]c1=O

Procedure:
Utilizing the procedures of Examples 50 and 51, 2′,3′-O-dibutylstannylene uridine (19.1 g) was treated with bromopentane (7 ml, 1.3 eq.) and sodium iodide (4.5 g) in DMF (90 ml). Purification on a silica gel column utilizing NeOH/CH2Cl2 5%→10% yielded the a mixture of 2′ and 3′ isomers; of the product as a dark oil (9.8 g).
Reaction SMILES: Br[C:2]1[C:12]2[O:11][CH2:10][CH2:9][N:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH3:20][C:21]([CH3:26])=[CH:22]B(O)O.C(=O)([O-])[O-].[Na+].[Na+].O>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>[CH3:22][C:21]([CH3:26])=[CH:20][C:2]1[C:12]2[O:11][CH2:10][CH2:9][N:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CCOc2c(Br)cccc2C1
Reactant: CC(C)=CB(O)O
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: COCCOC
Solvent: O
Product: CC(C)=Cc1cccc2c1OCCN(C(=O)OC(C)(C)C)C2
Temperature: 85 °C
Reaction time: 12 h
Yield: 89 %

Procedure:
A mixture of tert-butyl 9-bromo-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (328 mg, 1.00 mmol), 2,2-dimethylethenylboronic acid (98.0 mg, 1.00 mmol), saturated aqueous sodium carbonate solution (14 ml) and tetrakis(triphenylphosphine)palladium(0) (32.6 mg, 0.0282 mmol) in dimethoxyethane (10 ml) was stirred at 85° C. for 12 hr under a nitrogen atmosphere. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1) to give the desired product (270 mg, 89.1%) as an oil.
Reaction SMILES: N(S([O-])(=O)=O)(S([O-])(=O)=[O:4])[O].[K+].[K+].[K].[CH3:14][O:15][C:16]1[CH:17]=[C:18]([OH:22])[CH:19]=[CH:20][CH:21]=1>O.CC(C)=O>[CH3:14][O:15][C:16]1[C:21](=[O:4])[CH:20]=[CH:19][C:18](=[O:22])[CH:17]=1
Reactant: COc1cccc(O)c1
Reactant: [O]N(S(=O)(=O)[O-])S(=O)(=O)[O-]
Agent: [K+]
Agent: [K]
Solvent: CC(C)=O
Solvent: O
Product: COC1=CC(=O)C=CC1=O
Reaction time: 0.17 h
Yield: 117.5 %

Procedure:
A solution of potassium nitrosodisulfonate (0.75 g) and potassium monobasic phosphate (0.75 g) in water (37.5 ml) was added to m-methoxyphenol (109 mg, 0.9 mmol) in acetone (12.5 ml) and the resulting mixture was stirred vigorously for 10 minutes. Potassium nitrosodisulfonate (0.75 g) was added to the reaction mixture in two portions at 30 minute intervals and the stirring was continued for an additional two hours. After removal of acetone under reduced pressure, the resulting aqueous solution was extracted with dichloromethane (four 10 ml aliquots). The combined organic layers were washed with 0.01 N sodium hydroxide (10 ml) and then with water (10 ml) and then dried over anhydrous magnesium sulfate. The dried solution was filtered and the solvents removed under reduced pressure to yield 146.1 mg of 2 -methoxy-p-benzoquinone.
Reaction SMILES: Cl[CH:2]([CH2:6][CH2:7][Cl:8])[C:3](=[O:5])[CH3:4].[C:9]([S-:11])#[N:10].[Na+]>C(O)C>[S:11]([CH:2]([CH2:6][CH2:7][Cl:8])[C:3](=[O:5])[CH3:4])[C:9]#[N:10]
Reactant: N#C[S-]
Reactant: CC(=O)C(Cl)CCCl
Agent: [Na+]
Solvent: CCO
Product: CC(=O)C(CCCl)SC#N
Yield: 86.7 %

Procedure:
A solution of 7.8 g (0.05 moles) of 3,5-dichloro-2-pentanone with 4.15 g (0.051 moles) of sodium rhodanide in 50 cm3 of ethanol is boiled for 2 hours under stirring. Then the procedure described in Example 1 is followed. 7.7 g (87%) of 3-thiocyanato-5-chloro-2-pentanone are obtained, which is identical in all respect with the product of
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10](O)=[O:11])=[CH:7][C:6]=2[CH:13]=1.S(Cl)([Cl:16])=O>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10]([Cl:16])=[O:11])=[CH:7][C:6]=2[CH:13]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1cc2cc(Cl)ccc2o1
Product: O=C(Cl)c1cc2cc(Cl)ccc2o1

Procedure:
A solution of 5-chloro-1-benzofuran-2-carboxylic acid (827 mg, 42 mmol) in thionyl chloride (4 mL) was refluxed over night. The solvent was removed in vacuo to give the 5-chloro-1-benzofuran-2-carbonyl chloride in quantitative yield.
Reaction SMILES: [CH2:1]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9]Cl)=[CH:7][CH:6]=1)[CH:2]([CH3:4])[CH3:3].[Cl:13][C:14]1[CH:15]=[C:16]([CH2:21][C:22]([O:24]C)=[O:23])[CH:17]=[CH:18][C:19]=1[OH:20]>CO.O>[Cl:13][C:14]1[CH:15]=[C:16]([CH2:21][C:22]([OH:24])=[O:23])[CH:17]=[CH:18][C:19]=1[O:20][CH2:9][C:8]1[CH:11]=[CH:12][C:5]([CH2:1][CH:2]([CH3:4])[CH3:3])=[CH:6][CH:7]=1
Reactant: CC(C)Cc1ccc(CCl)cc1
Reactant: COC(=O)Cc1ccc(O)c(Cl)c1
Solvent: CO
Solvent: O
Product: CC(C)Cc1ccc(COc2ccc(CC(=O)O)cc2Cl)cc1

Procedure:
3-chloro-4-(4'-isobutylbenzyloxy) phenylacetic acid was prepared in accordance with the procedure designated (f) above by reacting 4-isobutylbenzyl chloride and methyl 3-chloro-4-hydroxyphenylacetate. The resultant product evidenced a melting point of 97°-99° C. (methanol-water 4:1), the yield being 61%.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([NH2:9])=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:17][S:18](Cl)(=[O:20])=[O:19]>ClCCl>[Cl:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([N:9]([S:18]([CH3:17])(=[O:20])=[O:19])[S:18]([CH3:17])(=[O:20])=[O:19])=[CH:4][CH:3]=1
Reactant: Cc1nc(Cl)ccc1N
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1nc(Cl)ccc1N(S(C)(=O)=O)S(C)(=O)=O
Temperature: 0 °C
Reaction time: 0.33 h

Procedure:
In a dry flask, 6-chloro-2-methylpyridin-3-amine (160 mg, 1.12 mmol) and triethylamine (470 μl, 3.37 mmol) were taken up in dichloromethane (5.6 ml) under argon. The solution was cooled to 0° C. and stirred for 20 minutes. Methanesulfonyl chloride (131 μl, 1.68 mmol) was added dropwise over 15 minutes. The mixture was allowed to warm to room temperature and stirred as such for 16 hours. The reaction was quenched with aqueous sodium bicarbonate and washed three times with ethyl acetate. The organic layers were combined, dried over anhydrous magnesium sulfate, and concentrated to afford the title compound.
Reaction SMILES: I[C:2]1[C:10]2[CH:9]=[N:8][CH:7]=[N:6][C:5]=2[N:4]([CH:11]([CH3:13])[CH3:12])[CH:3]=1.[Li]CCCC.[Br:19][C:20]1[C:21]([O:32][CH2:33][CH3:34])=[N:22][CH:23]=[C:24]([CH:31]=1)[C:25](N(OC)C)=[O:26]>C(OCC)C.CCCCCC>[Br:19][C:20]1[CH:31]=[C:24]([C:25]([C:2]2[C:10]3[CH:9]=[N:8][CH:7]=[N:6][C:5]=3[N:4]([CH:11]([CH3:13])[CH3:12])[CH:3]=2)=[O:26])[CH:23]=[N:22][C:21]=1[O:32][CH2:33][CH3:34]
Reactant: CC(C)n1cc(I)c2cncnc21
Reactant: CCOc1ncc(C(=O)N(C)OC)cc1Br
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: CCCCCC
Product: CCOc1ncc(C(=O)c2cn(C(C)C)c3ncncc23)cc1Br
Temperature: 25 °C
Reaction time: 1 h
Yield: 49 %

Procedure:
A solution of 5-Iodo-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidine (Preparation 93, 530 mg, 1.85 mmol) in anhydrous diethyl ether (8 mL) was cooled to −78° C. under nitrogen and n-BuLi (1 mL of a 2.03M solution in Hexane, 2.03 mmol) was added drop wise over a period of 10 min. Just after the completion of addition of n-BuLi, a solution of 5-Bromo-6-ethoxy-N-methoxy-N-methyl-nicotinamide (Preparation 240) in anhydrous diethyl ether (7 mL) was added slowly to the mixture and it was stirred at the same temperature for another 1 hour. The reaction mixture was warmed to room temperature and allowed to stir for another hour before being quenched with sat. aq. NH4Cl (15 mL). The mixture was extracted with EtOAc (3×15 mL), washed with water (20 mL), brine (15 mL), dried (Na2SO4) and evaporated in vacuo. The crude material was purified by column chromatography on silica gel (EtOAc:petroleum ether 2:10) to afford the title compound as a yellow gum in 49% yield, 350 mg.
Reaction SMILES: [OH:1][NH:2]/[C:3](=[N:14]\[H])/[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:13])([F:12])[F:11])[CH:5]=1.[O:16]=[C:17]1[C:22]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:21][CH2:20][CH2:19][N:18]1[CH2:35][C:36](O)=O.Cl.C(N=C=NCCCN(C)C)C>ClC(Cl)C>[C:29]1([C:22]2([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH2:21][CH2:20][CH2:19][N:18]([CH2:35][C:36]3[O:1][N:2]=[C:3]([C:4]4[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:13])([F:12])[F:11])[CH:5]=4)[N:14]=3)[C:17]2=[O:16])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: [H]/N=C(\NO)c1cccc(C(F)(F)F)c1
Reactant: O=C(O)CN1CCCC(c2ccccc2)(c2ccccc2)C1=O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CC(Cl)Cl
Product: O=C1N(Cc2nc(-c3cccc(C(F)(F)F)c3)no2)CCCC1(c1ccccc1)c1ccccc1
Temperature: 85 °C
Reaction time: 8 h

Procedure:
A solution of (Z)—N-hydroxy-3-(trifluoromethyl)benzimidamide (0.155 g, 0.761 mmol), 2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetic acid (0.214 g, 0.692 mmol; Example 68E) and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.172 g, 0.899 mmol) were stirred together in dichloroethane (0.5 mL) at room temperature for 3 hours. The reaction was then heated to 85° C. and stirred overnight. The reaction was cooled, loaded onto a SF15-12 column (Analogix®) and the product eluted using a gradient of 5% ethyl acetate/hexanes to 35% ethyl acetate over 30 minutes (Flow=30 mL/minute) to supply the title compound. 1H NMR (300 MHz, CDCl3) δ 8.40 (s, 1H), 8.31 (d, J=7.7, 1H), 7.80 (d, J=7.9, 1H), 7.64 (dd, J=6.4, 14.3, 1H), 7.39-7.10 (m, 10H), 4.89 (d, J=20.0, 2H), 3.70-3.56 (m, 2H), 2.70 (dt, J=11.5, 25.9, 2H), 1.92 (dtd, J=3.1, 6.4, 9.4, 2H).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:10].[C:17]([C:21]1[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1)([CH3:20])([CH3:19])[CH3:18]>>[C:9]([C:3]1[CH:4]=[C:5]([Cl:8])[CH:6]=[CH:7][C:2]=1[NH:1][S:27]([C:24]1[CH:25]=[CH:26][C:21]([C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:22][CH:23]=1)(=[O:29])=[O:28])(=[O:10])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: CC(C)(C)c1ccc(S(=O)(=O)Cl)cc1
Reactant: Nc1ccc(Cl)cc1C(=O)c1ccccc1
Product: CC(C)(C)c1ccc(S(=O)(=O)Nc2ccc(Cl)cc2C(=O)c2ccccc2)cc1

Procedure:
The title compound was prepared according to the general procedure for the synthesis of N-Aryl-benzenesulfonamides previously described using 115 mg of (2-amino-5-chloro-phenyl)-phenyl-methanone and 116 mg of 4-tert-Butyl-benzenesulfonyl chloride. 1H-NMR (400 MHz, CDCl3): δ 1.21 (s, 9H), 7.28-7.34 (m, 3H), 7.37-7.44 (m, 4H), 7.48 (dd, 1H, J=8.8, 2.4 Hz), 7.54-7.62 (m, 3H), 7.78 (d, 1H, J=8.8 Hz), 9.89 (s, 1H). MS: m/z 428.9 (M++1).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:9]=1[CH2:10][C:11](=[O:17])[NH:12]2.[N:18]1([CH2:23][CH2:24][NH:25][C:26]([C:28]2[C:32]([CH3:33])=[C:31]([CH:34]=O)[NH:30][C:29]=2[CH3:36])=[O:27])[CH:22]=[CH:21][N:20]=[N:19]1>C(O)C.N1CCCCC1>[N:18]1([CH2:23][CH2:24][NH:25][C:26]([C:28]2[C:32]([CH3:33])=[C:31]([CH:34]=[C:10]3[C:9]4[C:13](=[CH:14][CH:15]=[CH:16][C:8]=4[C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[F:1])[NH:12][C:11]3=[O:17])[NH:30][C:29]=2[CH3:36])=[O:27])[CH:22]=[CH:21][N:20]=[N:19]1
Reactant: Cc1[nH]c(C=O)c(C)c1C(=O)NCCn1ccnn1
Reactant: O=C1Cc2c(cccc2-c2ccccc2F)N1
Solvent: CCO
Solvent: C1CCNCC1
Product: Cc1[nH]c(C=C2C(=O)Nc3cccc(-c4ccccc4F)c32)c(C)c1C(=O)NCCn1ccnn1
Temperature: 25 °C
Reaction time: 72 h
Yield: 44.9 %

Procedure:
To a solution of 4-(2-fluoro-phenyl)-1,3-dihydro-indol-2-one (56.8 mg, 0.25 mmol) and 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-[1,2,3]triazol-1-yl-ethyl)-amide (67.9 mg, 0.26 mmol) in ethanol (2 mL) was added piperidine (3 drops). The reaction mixture was stirred at room temperature for three days. A yellow solid product was precipitated out, filtered, washed by ethanol for three times, and dried under high vacuum to provide pure product 5-[4-(2-fluoro-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-[1,2,3]triazol-1-yl-ethyl)-amide as a yellow solid (52.8 mg, 45%).
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8](Cl)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].[Cl:13][C:14]1[CH:15]=[N:16][CH:17]=[C:18]([Cl:33])[C:19]=1[CH2:20][C:21]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH3:32])[CH:24]=1)=[O:22]>>[Cl:33][C:18]1[CH:17]=[N:16][CH:15]=[C:14]([Cl:13])[C:19]=1/[CH:20]=[C:21](\[O:22][C:8](=[O:9])[C:7]1[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:12][CH:11]=1)/[C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH3:32])[CH:24]=1
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Reactant: COc1ccc(C(=O)Cc2c(Cl)cncc2Cl)cc1OC
Product: COc1ccc(/C(=C/c2c(Cl)cncc2Cl)OC(=O)c2ccc([N+](=O)[O-])cc2)cc1OC

Procedure:
The compound was obtained starting from 4-nitro-benzoyl chloride and 2-(3,5-dichloro-pyridin-4-yl)-1-(3,4-dimethoxy-phenyl)-ethanone, following the procedure of Example 7.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]=[O:11])=[CH:5][N:4]=1.[CH3:12][Si:13](Cl)([CH3:15])[CH3:14].C(N(CC)CC)C>C1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH:10]=[O:11])[Si:13]([CH3:15])([CH3:14])[CH3:12])=[CH:5][N:4]=1
Reactant: COc1ccc(NC=O)cn1
Reactant: C[Si](C)(C)Cl
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: COc1ccc(N(C=O)[Si](C)(C)C)cn1
Temperature: 10 °C
Yield: 87 %

Procedure:
N-(2-Methoxy-5-pyridyl)formamide (30.4 g, 0.2 mol) was added to 200 ml benzene. This was stirred with a mechanical stirrer under argon at 10° C. Trimethylsilyl chloride (25 g, 0.23 mol) was added. While stirring at 10° C., triethylamine (21 g, 0.21 mol) dissolved in 50 ml benzene was added dropwise over 0.5 hour. The slurry was warmed to room temperature and after 0.5 hour filtered. The salt cake was washed with 100 ml benzene and the combined filtrates concentrated on a rotary evaporator at 30° C. under aspirator vacuum. The dark liquid product was distilled under reduced pressure. A clear liquid, 39 g, 87% yield, (b.p. 87° C./0.25 mmHg). The product was stored under argon.
Reaction SMILES: [CH:1]1([C:6]2[CH:11]=[C:10]([F:12])[CH:9]=[CH:8][C:7]=2[OH:13])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.Cl[C:22]([O:24][CH3:25])=[O:23]>ClCCl>[C:22](=[O:23])([O:24][CH3:25])[O:13][C:7]1[CH:8]=[CH:9][C:10]([F:12])=[CH:11][C:6]=1[CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: Oc1ccc(F)cc1C1CCCC1
Reactant: COC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)Oc1ccc(F)cc1C1CCCC1
Temperature: 25 °C

Procedure:
2-Cyclopentyl-4-fluorophenol (1.70 g, 9.43 mmol) was dissolved in dichloromethane (20 mL) and triethylamine (2.6 mL, 18.85 mmol), cooled to 0° C., then treated with methyl chloroformate (1.09 mL, 14.14 mmol) and allowed to warm to room temperature over 16 h. The reaction was quenched with 3 mL saturated NaHCO3, washed with 50% saturated NaHCO3 (1×50 mL) and brine (1×50 mL), then dried over Na2SO4. Filtration followed by concentration yielded 2-cyclopentyl-4-fluorophenyl methyl carbonate as an oil which was used for the next step without purification. 1H NMR (400.0 MHz, CDCl3) δ 7.09-7.01 (m, 2H), 6.92-6.87 (m, 1H), 3.92 (s, 3H), 3.13 (dd, J=8.4, 17.2 Hz, 1H), 2.08-2.01 (m, 2H), 1.86-1.66 (m, 4H), 1.59-1.50 (m, 2H). MS (ESI) m/z (M+H+): 239.5.
Reaction SMILES: Cl.[F:2][C:3]([F:29])([F:28])[C:4]1[CH:5]=[C:6]([CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1)[CH2:7][O:8][C@H:9]1[CH2:14][CH2:13][NH:12][CH2:11][C@H:10]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[C:30](Cl)(=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>>[C:30]([N:12]1[CH2:13][CH2:14][C@H:9]([O:8][CH2:7][C:6]2[CH:21]=[C:22]([C:24]([F:27])([F:25])[F:26])[CH:23]=[C:4]([C:3]([F:2])([F:28])[F:29])[CH:5]=2)[C@H:10]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:11]1)(=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: FC(F)(F)c1cc(CO[C@H]2CCNC[C@H]2c2ccccc2)cc(C(F)(F)F)c1
Agent: Cl
Product: O=C(c1ccccc1)N1CC[C@H](OCc2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@H](c2ccccc2)C1
Yield: 91 %

Procedure:
The compound (0.15 g) obtained in Example 1 and benzoyl chloride (0.060 ml) were reacted and treated in the same manner as in the method described in Example 2 to obtain the title compound as colorless oil (0.16 g, 91%).
Reaction SMILES: [NH3:1].[Cl:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[C:8]([O:13][C:14]3[CH:27]=[CH:26][C:17]([O:18][CH:19]([CH3:25])[C:20](OCC)=[O:21])=[CH:16][CH:15]=3)[CH:9]=[N:10]2)=[CH:5][CH:4]=1>CC(C)=O>[Cl:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[C:8]([O:13][C:14]3[CH:27]=[CH:26][C:17]([O:18][CH:19]([CH3:25])[C:20]([NH2:1])=[O:21])=[CH:16][CH:15]=3)[CH:9]=[N:10]2)=[CH:5][CH:4]=1
Reactant: N
Reactant: CCOC(=O)C(C)Oc1ccc(Oc2cnc3cc(Cl)ccc3c2)cc1
Solvent: CC(C)=O
Product: CC(Oc1ccc(Oc2cnc3cc(Cl)ccc3c2)cc1)C(N)=O
Temperature: 60 °C
Reaction time: 8 h

Procedure:
Concentrated ammonia was added at 20° C. to a solution of ethyl 2-[4-(7-chloroquinolin-3-yloxy)phenoxy]propionate (3.0 g) (see Example 5) in acetone (50 ml) until the mixture just began to turn cloudy. The mixture was then heated at 60° C. for 8 hours and allowed to cool and stand overnight. Colourless crystals (1.5 g) 2-[4-(7-chloroquinolin-3-yloxy)phenoxy]propionamide were collected by filtration. The compound was characterised by its proton magnetic resonance spectrum. (Table 3).