Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:18]=[CH:17][C:5]2[N:6]=[C:7]([NH:9][C:10]([NH:12][CH2:13][CH2:14][CH2:15]Cl)=[O:11])[S:8][C:4]=2[CH:3]=1.[NH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1>C1COCC1.CCO>[Br:1][C:2]1[CH:18]=[CH:17][C:5]2[N:6]=[C:7]([NH:9][C:10]([NH:12][CH2:13][CH2:14][CH2:15][N:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[O:11])[S:8][C:4]=2[CH:3]=1
Reactant: O=C(NCCCCl)Nc1nc2ccc(Br)cc2s1
Reactant: C1CNCCN1
Solvent: CCO
Solvent: C1CCOC1
Product: O=C(NCCCN1CCNCC1)Nc1nc2ccc(Br)cc2s1
Temperature: 55 °C

Procedure:
To a mixture of N-(6-bromo-1,3-benzothiazol-2-yl)-N′-(3-chloropropyl)urea (100 mg, 0.287 mmol) in THF/EtOH (0.50/0.25 mL) was added piperazine (247 mg, 2.87 mmol). The reaction mixture was heated to about 55° C. for about 16 hrs. The crude reaction mixture was pumped down and purified by flash chromatography on SiO2.
Reaction SMILES: [CH2:1]([C:4]1[C:5]([O:16][CH3:17])=[C:6]([CH:11]=[C:12]([Cl:15])[C:13]=1[NH2:14])[C:7]([O:9][CH3:10])=[O:8])[CH:2]=[CH2:3].C1C[O:21]CC1>C1COCC1.COCCOCCOC>[OH:21][CH2:3][CH2:2][CH2:1][C:4]1[C:5]([O:16][CH3:17])=[C:6]([CH:11]=[C:12]([Cl:15])[C:13]=1[NH2:14])[C:7]([O:9][CH3:10])=[O:8]
Reactant: C1CCOC1
Reactant: C=CCc1c(N)c(Cl)cc(C(=O)OC)c1OC
Solvent: COCCOCCOC
Product: COC(=O)c1cc(Cl)c(N)c(CCCO)c1OC
Temperature: 20 °C
Reaction time: 0.5 h

Procedure:
A mixture of a 1M solution of BH3 in THF(8 ml) and the compound of step 3 above (2 g) in THF-diglyme (10 ml/16 ml) is stirred under N2 for 30 minutes at 20° C. Me3NO.2H2O (2.2 g) is added to the mixture and refluxed in a preheated oil bath allowing the THF to evaporate, followed by refluxing the mixture for one hour. The mixture is cooled to 20° C., partitioned between CHCl3 and sat'd aqueous NaHCO3, and stirred for 30 minutes. The organic layer is separated, washed with H2O, dried (MgSO4), evaporated and the residue is chromatographed on silica gel affording the desired product as a solid which is determined to be the correct product by NMR.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:41]([O-])=O)[C:18]([NH:19][CH:20]4[CH2:28][CH:27]5[CH:23]([CH2:24][C:25](=[O:40])[N:26]5[CH2:29][C:30]5[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][C:31]=5[O:38][CH3:39])[CH2:22][CH2:21]4)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl-].[NH4+].O>C(O)C.[Fe]>[NH2:41][C:17]1[C:18]([NH:19][CH:20]2[CH2:28][CH:27]3[CH:23]([CH2:24][C:25](=[O:40])[N:26]3[CH2:29][C:30]3[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][C:31]=3[O:38][CH3:39])[CH2:22][CH2:21]2)=[C:13]2[CH:12]=[CH:11][N:10]([S:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)(=[O:8])=[O:9])[C:14]2=[N:15][CH:16]=1
Reactant: COc1ccc(CN2C(=O)CC3CCC(Nc4c([N+](=O)[O-])cnc5c4ccn5S(=O)(=O)c4ccccc4)CC32)c(OC)c1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: COc1ccc(CN2C(=O)CC3CCC(Nc4c(N)cnc5c4ccn5S(=O)(=O)c4ccccc4)CC32)c(OC)c1
Temperature: 70 °C
Reaction time: 1.5 h
Yield: 92.9 %

Procedure:
To a solution of 6-(1-Benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-1-(2,4-dimethoxy-benzyl)-octahydro-indol-2-one (prepared as in Example 111) (152.3 mg, 0.2515 mmol) in ethanol (3 mL) was added ammonium chloride (59.0 mg, 1.10 mmol), iron powder (70.4 mg, 1.26 mmol), and water (5 mL). The reaction mixture was stirred at 70° C. for 1.5 hours. After cooling to room temperature, the reaction mixture was filtered through celite to remove iron and inorganic solids, rinsing with ethanol. The filtrate was neutralized with saturated aqueous sodium bicarbonate, and extracted twice with dichloromethane. The combined organic extracts were dried over magnesium sulphate, filtered, and evaporated in vacuo to yield 134.5 mg (93%) of 6-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-1-(2,4-dimethoxy-benzyl)-octahydro-indol-2-one, which was carried forward without purification. LCMS (Method E, ESI): RT=1.43 min, m+H=576.2.
Reaction SMILES: [C:1]([O:4][CH:5]([CH3:9])[C:6](O)=[O:7])(=[O:3])[CH3:2].C(Cl)(=O)C([Cl:13])=O>>[C:1]([O:4][CH:5]([CH3:9])[C:6]([Cl:13])=[O:7])(=[O:3])[CH3:2]
Reactant: CC(=O)OC(C)C(=O)O
Reactant: O=C(Cl)C(=O)Cl
Product: CC(=O)OC(C)C(=O)Cl

Procedure:
Stir a mixture of 2-acetoxy-propionic acid (550 g, 4.16 mol) in oxalyl chloride (500 mL) at room temperature for overnight. After removal of oxalyl chloride under vacuum, ˜700 g crude product is obtained (quantitative yield crude), which is used directly in the next step. 1H NMR (CDCl3, 400 MHz): δ 5.16 (m, 1H), 2.13 (s, 3H), 1.58 (d, J=7.2, 3H).
Reaction SMILES: Br[C:2]([C:5](=[O:11])[C:6]1[CH:10]=[CH:9][S:8][CH:7]=1)([CH3:4])[CH3:3].[N-:12]=[N+:13]=[N-:14].[Na+].O>CS(C)=O>[N:12]([C:2]([C:5](=[O:11])[C:6]1[CH:10]=[CH:9][S:8][CH:7]=1)([CH3:4])[CH3:3])=[N+:13]=[N-:14]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)(Br)C(=O)c1ccsc1
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CC(C)(N=[N+]=[N-])C(=O)c1ccsc1

Procedure:
0.87 of 2-bromo-2-(3-thenoyl)propane was dissolved in 5 ml of dimethyl sulfoxide, then 0.44 g of sodium azide was added thereto and reacted at 70° C. for 1 hour. After completion of the reaction, the reaction mixture was allowed to cool and put into 200 ml of water, and then extracted with ethyl ether. The organic layer was washed with water, then dried over magnesium sulfate, followed by concentration to obtain 0.70 g of 2-azido-2-(3-thenoyl)propane. The NMR spectrum data of this product were as follows.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][N:11]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]=[C:12]1[CH:20]([O:24][CH3:25])[C:21](O)=[O:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.Cl.[CH2:28]([O:35][C:36](=[O:48])[NH:37][C:38]([C:40]1[CH:45]=[CH:44][C:43]([CH2:46][NH2:47])=[CH:42][CH:41]=1)=[NH:39])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>>[CH2:28]([O:35][C:36](=[O:48])/[N:37]=[C:38](\[NH2:39])/[C:40]1[CH:41]=[CH:42][C:43]([CH2:46][NH:47][C:21](=[O:22])[CH:20]([C:12]2[N:11]([CH2:10][CH2:9][O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=3[N:13]=2)[O:24][CH3:25])=[CH:44][CH:45]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: COC(C(=O)O)c1nc2ccccc2n1CCOCc1ccccc1
Reactant: N=C(NC(=O)OCc1ccccc1)c1ccc(CN)cc1
Agent: Cl
Product: COC(C(=O)NCc1ccc(/C(N)=N/C(=O)OCc2ccccc2)cc1)c1nc2ccccc2n1CCOCc1ccccc1

Procedure:
According to general procedure C, (RS)-[1-(2-benzyloxy-ethyl)-1H-benzoimidazol-2-yl]-methoxy-acetic acid was reacted with [(4-aminomethyl-phenyl)-imino-methyl]-carbamic acid benzyl ester dihydrochloride (CAS 172348-75-3) to give (RS)-[1-amino-1-[4-({2-[1-(2-benzyloxy-ethyl)-1H-benzoimidazol-2-yl]-2-methoxy-acetylamino}-methyl)-phenyl]-meth-(Z)-ylidene]-carbamic acid benzyl ester. Off-white gum.
Reaction SMILES: [C:1]([N:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C@@H:7]([OH:14])[CH2:6][C@@H:5]1[CH3:15])(=[O:3])[CH3:2].[F:16][C:17]1[CH:18]=[C:19]([CH:21]=[CH:22][CH:23]=1)N>>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C@H:7]([O:14][C:22]2[CH:21]=[CH:19][CH:18]=[C:17]([F:16])[CH:23]=2)[CH2:6][C@@H:5]1[CH3:15])(=[O:3])[CH3:2]
Reactant: Nc1cccc(F)c1
Reactant: CC(=O)N1c2ccccc2[C@@H](O)C[C@@H]1C
Product: CC(=O)N1c2ccccc2[C@H](Oc2cccc(F)c2)C[C@@H]1C
Yield: 48 %

Procedure:
A compound was produced in the same manner as in Example 12, using 100 mg of trans-1-acetyl-4-hydroxy-2-methyl-1,2,3,4-tetrahydroquinoline and 112 mg of 3-fluoroaniline, and thus 70 mg (47%) of the title compound was obtained as a colorless oily substance.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[NH:17]1[CH:21]=[CH:20][N:19]=[CH:18]1.C>C1(C)C=CC=CC=1.[Cu].O>[N+:8]([C:4]1[CH:3]=[C:2]([N:17]2[CH:21]=[CH:20][N:19]=[CH:18]2)[CH:7]=[CH:6][CH:5]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1cccc(I)c1
Reactant: c1c[nH]cn1
Agent: [Cu]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: Cc1ccccc1
Product: O=[N+]([O-])c1cccc(-n2ccnc2)c1
Temperature: 200 °C
Reaction time: 16 h
Yield: 71.4 %

Procedure:
An intimate mixture of 1-iodo-3-nitrobenzene (24.9 g, 0.1 mol), copper bronze (320 mg, 5 mmol), potassium carbonate (15.2 g, 0.11 mol) and imidazole (15.0 g, 0.22 mol) was heated under a stream of nitrogen at 200° C. for 90 minutes. The reaction was cooled to 100° C., carefully treated with water (750 ml) and the resulting suspension stirred to ambient temperature over 16 hours. Filtration gave a grey-coloured solid which was dissolved in hot toluene (125 ml) and treated with decolourising charcoal (2 g). Filtration and cooling afforded 1-(3-nitrophenyl)-1H-imidazole as pale green needles (13.5 g, 71%). δH (360 MHz, CDCl3) 7.29 (1H, br s), 7.38 (1H, br s), 7.68-7.78 (2H, m), 7.97 (1H, br s), 8.23-8.29 (2H, m).
Reaction SMILES: [Cl:1][C:2]1[C:7](=[O:8])[NH:6][N:5]=[CH:4][C:3]=1[O:9][C:10]1[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=1[C:12]#[N:13].S(=O)(=O)(O)[OH:19]>>[Cl:1][C:2]1[C:7](=[O:8])[NH:6][N:5]=[CH:4][C:3]=1[O:9][C:10]1[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=1[C:12]([NH2:13])=[O:19]
Reactant: N#Cc1ccccc1Oc1cn[nH]c(=O)c1Cl
Reactant: O=S(=O)(O)O
Product: NC(=O)c1ccccc1Oc1cn[nH]c(=O)c1Cl
Temperature: 25 °C
Yield: 96 %

Procedure:
A solution of 2-(5-chloro-6-oxo-1,6-dihydro-pyridazin-4-yloxy)-benzonitrile (43.1 g, 0.17 mol) in concentrated sulfuric acid (150 mL) was stirred at 110° C. for 1 h and was then allowed to cool to 25° C. The reaction was added dropwise to ice water. The resulting precipitate was collected by filtration, washed with cold water and dried in vacuo to afford 2-(5-chloro-6-oxo-1,6-dihydro-pyridazin-4-yloxy)-benzamide (44.5 g, 96%) as a white solid; ESI-MS 266 [M+H+]; HPLC: >97% (purity). 1H-NMR (300 MHz, DMSO-d6) δ 13.38 (s, 1H), 7.81 (s, 2H), 7.62-7.65 (m, 1H), 7.47-7.55 (m, 2H), 7.33-7.38 (m, 1H), 7.24-7.27 (m, 1H).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([NH2:8])[CH:5]=[C:4]([C:9]2[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=2[O:16][CH3:17])[N:3]=1.[CH3:18][C:19]1[CH:20]=[CH:21][C:22]([NH2:25])=[CH:23][CH:24]=1>Cl>[Cl:15][C:13]1[CH:12]=[CH:11][C:10]([O:16][CH3:17])=[C:9]([C:4]2[N:3]=[C:2]([NH:25][C:22]3[CH:23]=[CH:24][C:19]([CH3:18])=[CH:20][CH:21]=3)[CH:7]=[C:6]([NH2:8])[CH:5]=2)[CH:14]=1
Reactant: COc1ccc(Cl)cc1-c1cc(N)cc(Cl)n1
Reactant: Cc1ccc(N)cc1
Agent: Cl
Product: COc1ccc(Cl)cc1-c1cc(N)cc(Nc2ccc(C)cc2)n1
Temperature: 190 °C
Yield: 79 %

Procedure:
A mixture of 2-chloro-6-(5-chloro-2-methoxy-phenyl)-pyridin-4-yl-amine, prepared in Example 1, (120 mg, 0.45 mmol) and p-tolylamine (1.0 g, 9.3 mmol) was heated at 190° C. for 45 minutes. After cooling to room temperature, the mixture was treated with hydrochloric acid (1 M, 50 ml). The mixture was extracted with ethyl acetate (50 ml). The organic extract was dried over magnesium sulfate and purified by flash chromatography on silica gel column eluting with ethyl acetate-hexane (1:4 followed by 1:1) to give the title compound (120 mg, 79% yield). 1H NMR (acetone-d6) δ 2.27 (s, 3H, CH3), 3.89 (s, 3H, CH3), 5.30 (d, 2H, J=6.4 Hz, NH2), 6.11 (d, 1H, J=1.7 Hz, Ar), 6.89 (d, 1H, J=1.7 Hz, Ar), 7.07 (d, 2H, J=8.3 Hz, Ar), 7.10 (d, 1H, J=8.8 Hz, Ar), 7.32 (dd, 1H, J=8.8 Hz, J=2.8 Hz, Ar), 7.51-7.54 (m, 2H, Ar), 7.68 (s, 1H, NH), 7.99 (d, 1H, J=2.8 Hz, Ar).
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([CH3:9])[C:3]=1[NH2:4].[CH3:10][O:11][CH2:12][CH:13]=O.CN(C)C>C1C=CC=CC=1.CO>[CH3:10][O:11][CH2:12][CH:13]=[N:4][C:3]1[C:5]([CH3:9])=[CH:6][CH:7]=[CH:8][C:2]=1[CH3:1]
Reactant: COCC=O
Reactant: Cc1cccc(C)c1N
Agent: CN(C)C
Solvent: c1ccccc1
Solvent: CO
Product: COCC=Nc1c(C)cccc1C

Procedure:
A solution of 24.2 (0.2 mole) of 2,6-dimethylaniline and 17.8 g (0.24 mole) of methoxy-acetaldehyde in 150 ml of benzene is treated with 1 ml of 25% trimethylamine solution in methanol and the mixture is refluxed for 5 hours using a steam trap. The reaction mixture is evaporated in vacuo and vacuum distillation of the residue yields the 1-(2'-methoxy-ethylidene-amino)-2,6-dimethylbenzene with a boiling point of 58°-61° C. at 0.1 Torr.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C(=O)([O-])[O-].[K+].[K+].[CH3:16][CH2:17][CH2:18]Br>CC(C)=O>[CH2:16]([O:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5])[CH2:17][CH3:18]
Reactant: N#Cc1ccccc1O
Reactant: CCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCOc1ccccc1C#N

Procedure:
75 g (630 mmol) of 2-hydroxybenzonitrile, 174 g (1.26 mol) of potassium carbonate and 232.3 g (1.89 mol) of n-propyl bromide in 11 of acetone are refluxed overnight. The solid is filtered off, the solvent is removed under reduced pressure and the residue is distilled under reduced pressure.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8](I)[C:7]([C:11]([F:14])([F:13])[CH3:12])=[CH:6][C:5]=1[NH2:15].[CH:17]([N:20]1[C:24]([Sn](CCCC)(CCCC)CCCC)=[CH:23][CH:22]=[N:21]1)([CH3:19])[CH3:18]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([C:24]2[N:20]([CH:17]([CH3:19])[CH3:18])[N:21]=[CH:22][CH:23]=2)[C:7]([C:11]([F:14])([F:13])[CH3:12])=[CH:6][C:5]=1[NH2:15]
Reactant: COC(=O)c1cc(I)c(C(C)(F)F)cc1N
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccnn1C(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: C1COCCO1
Product: COC(=O)c1cc(-c2ccnn2C(C)C)c(C(C)(F)F)cc1N
Temperature: 90 °C
Reaction time: 72 h
Yield: 18.4 %

Procedure:
To a solution of 2-amino-4-(1,1-difluoro-ethyl)-5-iodo-benzoic acid methyl ester (0.809 g, 2.37 mmol) in dioxane (10 mL) were added 1-isopropyl-5-tributylstannanyl-1H-pyrazole (1.14 g, 2.84 mmol) and Pd(PPh3)2Cl2 (170 mg, 0.237 mmol) and the resulting mixture was stirred at 90° C. for 72 h. The solvent was removed in vacuo to afford a dark oil. The crude product was purified by flash chromatography (silica gel, EtOAc/hexanes (0:10 to 3:7)) to give 2-amino-4-(1,1-difluoro-ethyl)-5-(2-isopropyl-2H-pyrazol-3-yl)-benzoic acid methyl ester (141 mg, 0.436 mmol, 18%) ES-MS: m/z 324 [M+H]+, rt 6.39 min.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([CH2:20][N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)=[CH:15][CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:34].C(N(CC)CC)C.[CH3:42][O:43][C:44]1[CH:49]=[C:48]([O:50][CH3:51])[CH:47]=[CH:46][C:45]=1[S:52](Cl)(=[O:54])=[O:53]>C(#N)C>[CH3:42][O:43][C:44]1[CH:49]=[C:48]([O:50][CH3:51])[CH:47]=[CH:46][C:45]=1[S:52]([O:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:27]([O:29][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:28])[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([CH2:20][N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)=[CH:15][CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:34])(=[O:53])=[O:54]
Reactant: COc1ccc(S(=O)(=O)Cl)c(OC)c1
Reactant: CC(C)(C)OC(=O)n1c(-c2ccc(O)c3c2C(=O)NC3)cc2cc(CN3CCCCC3)ccc21
Solvent: CCN(CC)CC
Solvent: CC#N
Product: COc1ccc(S(=O)(=O)Oc2ccc(-c3cc4cc(CN5CCCCC5)ccc4n3C(=O)OC(C)(C)C)c3c2CNC3=O)c(OC)c1
Yield: 28.2 %

Procedure:
In a similar manner to Step 1 of Example 233, 4-hydroxy-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (0.0289 g, 0.0626 mmol) was dissolved in acetonitrile (0.650 mL), and the solution was treated with triethylamine (0.0540 mL, 0.390 mmol) and 2,4-dimethoxybenzenesulfonyl chloride (0.0462 g, 0.195 mmol) to obtain 4-(2,4-dimethoxybenzenesulfonyloxy)-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (0.0117 g, yield 20%).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([O:12][CH3:13])=[O:11])=[N:2]1.[Cl:14][C:15]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:16]=1[CH2:17]Cl.C([O-])([O-])=O.[K+].[K+]>CC(C)=O.C(Cl)Cl>[CH3:13][O:12][C:10]([C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[N:1]([CH2:17][C:16]2[CH:19]=[CH:20][C:21]([Cl:23])=[CH:22][C:15]=2[Cl:14])[N:2]=1)=[O:11]
Reactant: ClCc1ccc(Cl)cc1Cl
Reactant: COC(=O)c1n[nH]c2ccccc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CC(C)=O
Product: COC(=O)c1nn(Cc2ccc(Cl)cc2Cl)c2ccccc12
Temperature: 70 °C
Reaction time: 8 h

Procedure:
Next, a mixture of methyl indazole-3-carboxylate (2.05 g, 11.4 mmol), 2,4-dichlorobenzyl chloride (3.35 mL, 12.54 mml), and K2CO3 (7.0 g, 50 mmol) in acetone (22 mL) was refluxed overnight at a temperature of 70° C. The reaction mixture was cooled to room temperature, filtered, and the residue was washed with acetone. The combined filtrate was concentrated under vacuum (rotovapor). The solid thus obtained was dissolved in CH2Cl2 and filtered to remove any undissolved solid. The solution was then concentrated, diluted with hexane and left in the refrigerator overnight. The precipitated solid was then filtered, washed with a mixture of hexane/ethyl acetate (9:1) to yield the pure product as a white solid. Yield=3.5 g (89%); m.p.=144°-146° C.; 1H NMR (400 MHz, CDCl3) δ 8.31 (d, J=8.8 Hz, 1H), 7.39-7.47 (m, 4H), 7.12 (d, J=8.8 Hz, 1H), 6.71 (d, J=8.8 Hz, 1H), 5.81 (s, 2H), 4.11 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:44])[N:5]([C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:38]#[C:39][Si](C)(C)C)[CH:33]=1)[C:6]([CH:12]([NH:14][C:15]1[N:23]=[CH:22][N:21]=[C:20]3[C:16]=1[N:17]=[CH:18][N:19]3COCC[Si](C)(C)C)[CH3:13])=[N:7]2.Cl.C[OH:47]>>[C:38]([C:34]1[CH:33]=[C:32]([N:5]2[C:4](=[O:44])[C:3]3[C:8](=[CH:9][CH:10]=[CH:11][C:2]=3[CH3:1])[N:7]=[C:6]2[CH:12]([NH:14][C:15]2[N:23]=[CH:22][N:21]=[C:20]3[C:16]=2[N:17]=[CH:18][NH:19]3)[CH3:13])[CH:37]=[CH:36][CH:35]=1)(=[O:47])[CH3:39]
Reactant: Cc1cccc2nc(C(C)Nc3ncnc4c3ncn4COCC[Si](C)(C)C)n(-c3cccc(C#C[Si](C)(C)C)c3)c(=O)c12
Reactant: CO
Agent: Cl
Product: CC(=O)c1cccc(-n2c(C(C)Nc3ncnc4[nH]cnc34)nc3cccc(C)c3c2=O)c1

Procedure:
Compound 139 was treated with 4N HCl in MeOH at 70° C. for 16 hours in accordance with the procedure described for compound 0.121 (step D). This reaction afforded compound 144, the structure of which is shown below. m/z=440 (M+H)
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[N:10]([OH:17])[C:9]=2[C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[CH:4][CH:3]=1.[N+](=[CH2:26])=[N-]>C(Cl)(Cl)Cl.CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[N:10]([O:17][CH3:26])[C:9]=2[C:18]2[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=2)=[CH:6][CH:7]=1
Reactant: C=[N+]=[N-]
Reactant: On1c(-c2ccncc2)c(-c2ccc(F)cc2)c2ncccc21
Solvent: ClC(Cl)Cl
Solvent: CO
Product: COn1c(-c2ccncc2)c(-c2ccc(F)cc2)c2ncccc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 3-(4-fluorophenyl)-1-hydroxy-2-(pyridin-4yl)-1H-pyrrolo[3,2-b]pyridine (0.38 g, 1.25 mmol) in chloroform (8 ml) and methanol (2 ml) was added to a solution of diazomethane at 0° C. The reaction was warmed to room temperature and stirred overnight. The solvent was removed in vacuo and the residue was purified by flash column chromatography (50%-100% ethyl acetate/hexanes gradient) to 3-(4-fluorophenyl)-1-methoxy-2-(pyridin-4-yl)-1H-pyrrolo[3,2-b]pyridine as an off white solid (210 mg).
Reaction SMILES: [CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:17]([CH3:23])[NH:18][C:19](=[O:22])[NH:20][N:21]=2)=[CH:12][CH:11]=1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[CH2:1]([NH:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2[CH:17]([CH3:23])[NH:18][C:19](=[O:22])[NH:20][N:21]=2)=[CH:14][CH:15]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC1NC(=O)NN=C1c1ccc(N)cc1
Reactant: O=Cc1ccccc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: CC1NC(=O)NN=C1c1ccc(NCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 98.3 %

Procedure:
Benzaldehyde (0.25 g) was added to a solution of 6-(4-aminophenyl)-5-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one (0.48 g) in methanol (45 ml), and the mixture was stirred for 1.5 hours at room temperature. Acetic acid (0.13 ml) was added thereto and then a solution of sodium cyanoborohydride (0.1 g) in methanol (0.7 ml) was added dropwise with stirring. After adding, the reaction mixture was warmed at 50° C. for 2 hours under stirring and evaporated in vacuo. An aqueous solution of sodium bicarbonate was added to the residue and the mixture was triturated to give 6-(4-benzylaminophenyl)-5-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one (0.68 g).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:7]=[C:8](Br)[C:9]=1[O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH:5]=[O:6].O[C:21]1C=C(C=CC=1)C=O>>[CH3:21][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH:5]=[O:6]
Reactant: CCCCCCCCOc1c(Br)cc(C=O)cc1Br
Reactant: O=Cc1cccc(O)c1
Product: CCCCCCCCOc1ccc(C=O)cc1C

Procedure:
The title compound was prepared using a procedure analogous to Aldehyde 3 substituting 3-methyl-4-hydroxybenzaldehyde for 3-hydroxybenzaldehyde.
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]([F:34])([F:33])[C:7]([F:32])([F:31])[C:8]([F:30])([F:29])[C:9]([F:28])([F:27])[C:10]([F:26])([F:25])[C:11]([F:24])([F:23])[C:12]([F:22])([F:21])[C:13]([F:20])([F:19])[CH2:14][CH2:15][CH2:16][CH2:17]Br.[OH:35][C:36]1[CH:41]=[CH:40][C:39]([C:42]2[CH:47]=[CH:46][C:45]([C:48]#[N:49])=[CH:44][CH:43]=2)=[CH:38][CH:37]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Br:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]([F:34])([F:33])[C:7]([F:31])([F:32])[C:8]([F:30])([F:29])[C:9]([F:27])([F:28])[C:10]([F:25])([F:26])[C:11]([F:23])([F:24])[C:12]([F:22])([F:21])[C:13]([F:19])([F:20])[CH2:14][CH2:15][CH2:16][CH2:17][O:35][C:36]1[CH:37]=[CH:38][C:39]([C:42]2[CH:47]=[CH:46][C:45]([C:48]#[N:49])=[CH:44][CH:43]=2)=[CH:40][CH:41]=1
Reactant: N#Cc1ccc(-c2ccc(O)cc2)cc1
Reactant: FC(F)(CCCCBr)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)CCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: N#Cc1ccc(-c2ccc(OCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)CCCCBr)cc2)cc1

Procedure:
A solution of 1,16-dibromo-5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12-hexadecafluorohexadecane (20.16 g), 4'-hydroxy-4-cyanobiphenyl (2.05 g), potassium carbonate (2.07 g) and acetone (30 mL) is refluxed for 8 hrs. The acetone is removed under reduced pressure and the residue diluted with water and extracted with ethyl ether. The extracts are washed with water and brine, dried (MgSO4), concentrated, and purified by chromatography to give 4'-(16-bromo-5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12-hexadecafluorohexadecyloxy)-4-cyanobiphenyl.
Reaction SMILES: [CH2:1]([O:8][C:9]([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:23]([O:25][C:26]1[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][CH:27]=1)=[O:24].O>C1COCC1>[N+:32]([C:29]1[CH:28]=[CH:27][C:26]([O:25][C:23]([N:13]2[C:14]3[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:11]([C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:10])=[CH:12]2)=[O:24])=[CH:31][CH:30]=1)([O-:34])=[O:33]
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Reactant: O=C(OCc1ccccc1)c1c[nH]c2ccccc12
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: O=C(OCc1ccccc1)c1cn(C(=O)Oc2ccc([N+](=O)[O-])cc2)c2ccccc12
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
To a solution of 1H-indole-3-carboxylic acid benzyl ester (100 mg, 0.398 mmol) in dry THF (2 mL) at 0° C. under nitrogen was added NaH (60% in mineral oil, 32 mg, 0.796 mmol). The resulting solution was stirred at 0° C. for 10 min, and added dropwise to a stirred solution of 4-nitrophenyl chloroformate (160 mg, 0.796 mmol) in dry THF (2 mL) cooled at 0° C. The resulting solution was stirred at RT under nitrogen for 48 h. The mixture was poured into water and extracted twice with CH2Cl2. The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude residue was successively purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 7:3) and by preparative HPLC (Waters SunFire C18-ODB, 5 μm, 19×50 mm, 20% CH3CN/H2O 2.5 min, 20-100% CH3CN/H2O in 10 min, CH3CN/H2O containing 0.1% HCOOH flow: 20 mL/min) to give after extraction of the pure fractions the desired compound. TLC, Rf (c-hexane/EtOAc 1:1)=0.8; MS (LC/MS): 439.0 [M+Na]+; tR (HPLC conditions a): 4.58 min.