Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:6]([NH:7][C:8](=O)[CH3:9])=[CH:5][N:4]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[N:3]=1.B(F)(F)F.CCOCC.[BH4-].[Na+].Cl.C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C.O1CCCC1>[Cl:1][C:2]1[C:6]([NH:7][CH2:8][CH3:9])=[CH:5][N:4]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[N:3]=1
Reactant: CC(=O)Nc1cn(-c2cccnc2)nc1Cl
Agent: Cl
Agent: FB(F)F
Agent: O=C([O-])O
Solvent: CCOC(C)=O
Solvent: O
Solvent: CCOCC
Product: CCNc1cn(-c2cccnc2)nc1Cl
Temperature: 60 °C
Reaction time: 0.25 h
Yield: 78.6 %

Procedure:
A 100 mL 3-neck round bottom flask was charged with N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)acetamide (475 mg, 2.01 mmol) and tetrahydrofuran (10 mL). borontrifluoride etherate (0.63 mL, 5.02 mmol) was added and the mixture was stirred for 15 minutes to give a suspension. Sodium borohydride (228 mg, 6.02 mmol) was added and the reaction was heated at 60° C. for 4 hours, at which point thin layer chromatography analysis [Eluent: ethyl acetate, sample was prepared by treatment of reaction mixture with hydrochloric acid, followed by sodium bicarbonate basification and ethyl acetate extraction] indicated that the reaction was complete. Water (10 mL) and concentrated hydrochloric acid (1 mL) were added and the reaction was heated at 60° C. for 1 hour. The reaction mixture was cooled to room temperature and distilled to remove tetrahydrofuran. The mixture was neutralized with saturated aqueous sodium bicarbonate to pH˜8 to afford a suspension, which was stirred for 1 hour and filtered. The filter cake was rinsed with water (10 mL) and dried under vacuum to afford a white solid (352 mg, 79%): mp 93-96° C.; 1H NMR (400 MHz, DMSO-d6) δ 8.99 (d, J=2.7 Hz, 1H), 8.44 (dd, J=4.6, 1.4 Hz, 1H), 8.10 (ddd, J=8.4, 2.7, 1.4 Hz, 1H), 8.06 (s, 1H), 7.50 (dd, J=8.4, 4.7 Hz, 1H), 4.63 (t, J=6.0 Hz, 1H), 3.06-2.92 (m, 2H), 1.18 (t, J=7.1 Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ 146.17, 138.31, 135.81, 132.82, 130.84, 124.10, 123.96, 112.23, 40.51, 14.28; EIMS m/z 222 ([M]+).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([C@H:11]1[CH2:15][N:14]([C:16]([C:18]2([C:21]3[C:26]([F:27])=[CH:25][C:24]([Cl:28])=[CH:23][N:22]=3)[CH2:20][CH2:19]2)=[O:17])[C@H:13]([C:29](O)=[O:30])[CH2:12]1)(=[O:10])=[O:9].[NH2:32][C@@H:33]([CH2:42][CH2:43][CH3:44])[C@H:34]([OH:41])[C:35]([NH:37][CH:38]1[CH2:40][CH2:39]1)=[O:36]>>[Cl:28][C:24]1[CH:25]=[C:26]([F:27])[C:21]([C:18]2([C:16]([N:14]3[CH2:15][C@H:11]([S:8]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[Cl:1])(=[O:9])=[O:10])[CH2:12][C@H:13]3[C:29]([NH:32][C@@H:33]([CH2:42][CH2:43][CH3:44])[C:34](=[O:41])[C:35]([NH:37][CH:38]3[CH2:40][CH2:39]3)=[O:36])=[O:30])=[O:17])[CH2:20][CH2:19]2)=[N:22][CH:23]=1
Reactant: CCC[C@H](N)[C@H](O)C(=O)NC1CC1
Reactant: O=C(O)[C@@H]1C[C@@H](S(=O)(=O)c2ccccc2Cl)CN1C(=O)C1(c2ncc(Cl)cc2F)CC1
Product: CCC[C@H](NC(=O)[C@@H]1C[C@@H](S(=O)(=O)c2ccccc2Cl)CN1C(=O)C1(c2ncc(Cl)cc2F)CC1)C(=O)C(=O)NC1CC1

Procedure:
The title compound was prepared in analogy to Example 1, using (2S,4R)-4-(2-chloro-benzenesulfonyl)-1-[1-(5-chloro-3-fluoro-pyridin-2-yl)-cyclopropanecarbonyl]-pyrrolidine-2-carboxylic acid and (2S,3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide in step 1. MS (m/e)=653.14 [M+H+].
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][CH:4]=1)#[N:2].[Cl:12][C:13]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[C:15]([Cl:23])[C:14]=1[NH:24][NH2:25].[OH-].[Na+]>C(Cl)Cl>[Cl:12][C:13]1[CH:18]=[C:17]([C:19]([F:21])([F:20])[F:22])[CH:16]=[C:15]([Cl:23])[C:14]=1[NH:24][NH:25][C:7](=[O:8])[C:6]1[CH:10]=[CH:11][C:3]([C:1]#[N:2])=[CH:4][CH:5]=1
Reactant: NNc1c(Cl)cc(C(F)(F)F)cc1Cl
Reactant: N#Cc1ccc(C(=O)Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: N#Cc1ccc(C(=O)NNc2c(Cl)cc(C(F)(F)F)cc2Cl)cc1
Reaction time: 16 h

Procedure:
A solution of 14.2 g of 4-cyanobenzoyl chloride in 100 ml of methylene chloride is added dropwise with stirring at from 10 to 15° in the course of approximately 30 minutes to 20 g of 2,6-dichloro-4-trifluoromethylphenylhydrazine in 250 ml of dichloromethane, and the mixture is stirred for a further 16 hours. 36 ml of aqueous sodium hydroxide solution (10%) is then run in with vigorous stirring. 100 ml of methylene chloride are added, the organic phase is washed three times using in each case 100 ml of water and dried over sodium sulfate, and the solvent is removed on a rotary evaporator. After the residue has been recrystallized from toluene, the title product of melting point 185-186° is obtained (compound no. 1.6).
Reaction SMILES: C1COCC1.[C:6]1([Li])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.Cl[C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[C:21]([O:24][CH3:25])[CH:22]=2)[C:17]([CH2:26][C:27]2[O:28][CH:29]=[CH:30][CH:31]=2)=[N:16][N:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(OCC)(=O)C.[Cl-].[Cl-].[Zn+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:28]1[CH:29]=[CH:30][CH:31]=[C:27]1[CH2:26][C:17]1[C:18]2[C:23](=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[C:14]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)=[N:15][N:16]=1
Reactant: COc1ccc2c(Cc3ccco3)nnc(Cl)c2c1
Reactant: [Li]c1ccccc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: [Cl-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COc1ccc2c(Cc3ccco3)nnc(-c3ccccc3)c2c1
Reaction time: 1 h
Yield: 34.7 %

Procedure:
A solution under N2 of ZnCl2 in THF 0.5M (18.35 ml, 9.18 mmoles) was dropwise added under stirring at 0° C. with 2M phenyl lithium (4.37 ml, 8.74 mmoles). The mixture was left at room temperature for 1 hour, then sequentially added with 4-chloro-1-furan-2-ylmethyl-6-methoxy-phthalazine (1.2 g, 4.37 mmoles), prepared as described in example 127, palladium acetate (49 mg, 0.218 mmole) and triphenylphosphine (114.4 mg, 4.36 mmoles). The mixture was refluxed for 45 minutes, then diluted with ethyl acetate and washed with water. The organic phase was anhydrified over Na2SO4 and dried. The residue was flash chromatographed (eluent: petrolatum/ethyl acetate 1:1). The resultant oil was crystallised from ethyl ether (15 ml) to give 480 mg of the title compound (yield: 34%). m.p.: 128-129° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:10][C:9](=[O:11])[O:8][C:7](=[O:12])[C:6]=2[C:13]=1[O:14]C.[Al+3].[Cl-].[Cl-].[Cl-]>ClCCl.[Cl-].[Na+].O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:10][C:9](=[O:11])[O:8][C:7](=[O:12])[C:6]=2[C:13]=1[OH:14]
Reactant: COc1c(Br)ccc2[nH]c(=O)oc(=O)c12
Agent: [Al+3]
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: O=c1[nH]c2ccc(Br)c(O)c2c(=O)o1
Temperature: 25 °C
Reaction time: 8 h
Yield: 94.9 %

Procedure:
A mixture of Example 385B (20 g) in dichloromethane (600 mL) at 0° C. was treated with AlCl3 (39 g, 293 mmol) in several portions and stirred vigorously overnight at room temperature. The mixture was treated with brine (300 mL), stirred for 10 minutes, and extracted with ethyl acetate. The extract was dried (MgSO4), filtered, and concentrated to provide the desired product (18 g) which was used directly in the next step.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Cl:7][C:8]1[N:9]=[N:10][C:11](Cl)=[CH:12][CH:13]=1>>[Cl:7][C:8]1[N:9]=[N:10][C:11]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)=[CH:12][CH:13]=1
Reactant: Clc1ccc(Cl)nn1
Reactant: C1COCCN1
Product: Clc1ccc(N2CCOCC2)nn1
Temperature: 90 °C
Yield: 79.1 %

Procedure:
A 50 mL flask equipped with a reflux condenser was charged with morpholine (2.93 mL, 33.5 mmol) and 3,6-dichloropyridazine (5.00 g, 33.5 mmol). The mixture was heated at 90° C. for 6 h, the resultant solid was partitioned between EtOAc, water and saturated NH4Cl. Organic layer was separated, dried over anhydrous Na2SO4, filtered, and evaporated to afford the title compound 64 (5.3 g, 26.5 mmol, 79% yield).
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([O:39][CH3:40])=[C:7]([CH:38]=1)[CH2:8][C@@H:9]1[C:15](=[O:16])[N:14]([C:17]([NH:19][C@@H:20]([C:24]2[CH:32]=[CH:31][C:27]([C:28]([OH:30])=[O:29])=[C:26]([N+:33]([O-])=O)[CH:25]=2)[CH2:21][CH2:22][CH3:23])=[O:18])[CH2:13][C:12](=[N:36][OH:37])[NH:11][CH2:10]1>[Zn].C(O)(=O)C>[NH2:33][C:26]1[CH:25]=[C:24]([C@H:20]([NH:19][C:17]([N:14]2[C:15](=[O:16])[C@@H:9]([CH2:8][C:7]3[CH:38]=[C:3]([Cl:2])[CH:4]=[CH:5][C:6]=3[O:39][CH3:40])[CH2:10][NH:11][C:12](=[N:36][OH:37])[CH2:13]2)=[O:18])[CH2:21][CH2:22][CH3:23])[CH:32]=[CH:31][C:27]=1[C:28]([OH:30])=[O:29]
Reactant: CCC[C@@H](NC(=O)N1CC(=NO)NC[C@H](Cc2cc(Cl)ccc2OC)C1=O)c1ccc(C(=O)O)c([N+](=O)[O-])c1
Agent: Cl
Agent: [Zn]
Solvent: CC(=O)O
Product: CCC[C@@H](NC(=O)N1CC(=NO)NC[C@H](Cc2cc(Cl)ccc2OC)C1=O)c1ccc(C(=O)O)c(N)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 69.2 %

Procedure:
To the compound 97 (1.74 g) in an acetic acid (35 ml) suspension, zinc powder (3.5 g) was added, and the mixture was stirred at room temperature for 4 hours. The insolubles were filtered out and the filtrate was concentrated in vacuo. To the residue, acetic acid (20 ml) was added, the mixture was stirred at 60° C. for 1 hour, then the insolubles were filtered out. The filtrate was concentrated in vacuo, the residue was diluted with chloroform-methanol-acetic acid (5:1:0.1) (20 ml), and tha mixture was stirred at room temperature for 1 hour. The insolubles were collected by filtration, then ethyl acetate (105 ml), saturated aqueous ammonium chloride solution (105 ml), and water (53 ml) were added to the obtained crystals, and the mixture was stirred at room temperature for 4 hours. The layers were separated, and the aqueous layer was extracted with ethyl acetate (50 ml×2). The organic layer and the extract were combined, then the mixture was washed with brine, dried over sodium sulfate, then concentrated. The residue was purified by flash column chromatography (silica gel, chloroform/ethyl acetate/methanol=50/50/5 to 50/50/10) to obtain 2-amino-4-[(1R)-1-({[(6S)-6-(5-chloro-2-methoxybenzyl)-3-(hydroxyimino)-7-oxo-1,4-diazepan-1-yl]carbonyl}amino)butyl]benzoic acid (compound 14) (1.07 g).
Reaction SMILES: Br[C:2]1[CH:19]=[CH:18][C:5]2[N:6]=[C:7]([N:9]3[CH2:14][CH2:13][N:12]([CH:15]4[CH2:17][CH2:16]4)[CH2:11][CH2:10]3)[S:8][C:4]=2[CH:3]=1.B(O)(O)[C:21]1[C:26]([Cl:27])=[CH:25][N:24]=[C:23]([O:28][CH3:29])[CH:22]=1.CC(O[K])=O>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:27][C:26]1[C:21]([C:2]2[CH:19]=[CH:18][C:5]3[N:6]=[C:7]([N:9]4[CH2:14][CH2:13][N:12]([CH:15]5[CH2:17][CH2:16]5)[CH2:11][CH2:10]4)[S:8][C:4]=3[CH:3]=2)=[CH:22][C:23]([O:28][CH3:29])=[N:24][CH:25]=1
Reactant: Brc1ccc2nc(N3CCN(C4CC4)CC3)sc2c1
Reactant: COc1cc(B(O)O)c(Cl)cn1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: CC(=O)O[K]
Solvent: CN(C)C=O
Product: COc1cc(-c2ccc3nc(N4CCN(C5CC5)CC4)sc3c2)c(Cl)cn1
Temperature: 80 °C
Yield: 5.9 %

Procedure:
To a solution of 6-bromo-2-(4-cyclopropylpiperazin-1-yl)benzothiazole (500 mg, 1.48 mmol) and 5-chloro-2-methoxypyridin-4-yl-4-boronic acid (334 mg, 1.78 mmol) in DMF (20 mL) was added PdCl2(dppf) (108 mg, 0.148 mmol), followed by CH3COOK (581 mg, 5.92 mmol). The mixture was heated at 80° C. for 2 h, filtered and the volatiles evaporated. Water (5 mL) was added and the mixture was extracted with CH2Cl2 (3×5 mL). The combined organic extracts were dried (Na2SO4) and concentrated. The residue was purified by the preparative HPLC to give 35 mg (6%) of 6-(5-chloro-2-methoxypyridin-4-yl)-2-(4-cyclopropylpiperazin-1-yl)benzothiazole as a trifluoroacetate salt.
Reaction SMILES: CCOCC.Cl[C:7]1[N:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[C:9]([Cl:17])[N:8]=1.[CH2:18]([O:20][P:21]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([NH2:33])=[C:29]([CH3:34])[CH:28]=1)(=[O:25])[O:22][CH2:23][CH3:24])[CH3:19].C(N(C(C)C)CC)(C)C>ClC(Cl)C.C(O)(C)(C)C.[Cl-].[Zn+2].[Cl-]>[Cl:17][C:9]1[C:10]([C:13]([F:16])([F:15])[F:14])=[CH:11][N:12]=[C:7]([NH:33][C:30]2[CH:31]=[CH:32][C:27]([CH2:26][P:21](=[O:25])([O:20][CH2:18][CH3:19])[O:22][CH2:23][CH3:24])=[CH:28][C:29]=2[CH3:34])[N:8]=1
Reactant: CCOP(=O)(Cc1ccc(N)c(C)c1)OCC
Reactant: FC(F)(F)c1cnc(Cl)nc1Cl
Agent: [Cl-]
Agent: [Zn+2]
Solvent: CCOCC
Solvent: CC(C)(C)O
Solvent: CC(Cl)Cl
Product: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Cl)n2)c(C)c1)OCC
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A 1M solution of zinc chloride in ether (12.8 mL, 12.8 mmol) was added to a solution of 2,6-dichloro-5-trifluoromethylpyrimidine (2.76 gm, 12.8 mmol) in 20 mL of dichloroethane and t-butanol (1:1) under an atmosphere of nitrogen. The reaction mixture was stirred at rt for 30 min, cooled to 0° C. and then treated with a solution of (4-amino-3-methyl benzyl)phosphonic acid diethyl ester (Compound 33D, 2.2 gm, 8.5 mmol) in dichloroethane and t-butanol (10 mL, 1:1) slowly over 10 min through an addition funnel. After 1 hour, diisopropylethylamine (2.2 mL, 12.6 mmol) was added and then reaction gradually warmed up to rt over 4 hrs. The reaction mixture was refrigerated overnight causing the desired product to precipitate out of solution. This was collected by filtration to afford 2.7 g of the title compound (73%). 1H NMR (300 MHz, CDCl3): δ 1.21-1.26 (m, 6H), 2.3 (s, 3H), 3.15 (d, J=22.0 Hz, 2H), 3.99-4.09 (m, 4H), 7.17 (m, 3H), 7.72 (d, J=7.5 Hz, 1H), 8.52 (s, 1H).
Reaction SMILES: C1(N=[N:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[N:21]=[C:20]([NH:22][C:23]4[CH:28]=[CH:27][C:26]([N:29]=NC5C=CC=CC=5)=[CH:25][CH:24]=4)[N:19]=[C:18]([NH:37][C:38]4[CH:43]=[CH:42][C:41]([N:44]=NC5C=CC=CC=5)=[CH:40][CH:39]=4)[N:17]=3)=[CH:11][CH:10]=2)C=CC=CC=1.O.NN.NC1C=CC=CC=1>[Pd].C(O)C(C)C>[NH2:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[N:21]=[C:20]([NH:22][C:23]3[CH:24]=[CH:25][C:26]([NH2:29])=[CH:27][CH:28]=3)[N:19]=[C:18]([NH:37][C:38]3[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][CH:39]=3)[N:17]=2)=[CH:11][CH:10]=1
Reactant: c1ccc(N=Nc2ccc(Nc3nc(Nc4ccc(N=Nc5ccccc5)cc4)nc(Nc4ccc(N=Nc5ccccc5)cc4)n3)cc2)cc1
Agent: [Pd]
Agent: NN
Solvent: Nc1ccccc1
Solvent: O
Solvent: CC(C)CO
Product: Nc1ccc(Nc2nc(Nc3ccc(N)cc3)nc(Nc3ccc(N)cc3)n2)cc1
Temperature: 70 °C
Reaction time: 2 h

Procedure:
In one 100 milliliter, four-neck, round-bottom flask equipped with a thermo-couple, a condenser, a mechanical stirrer, and a nitrogen sweep were placed 3.34 grams (0.005 mole) of 2,4,6-tris-[4-(phenylazo)phenylamino]-1,3,5-triazine, 50 grams of isobutanol, 1.66 grams (0.033 mole) of hydrazine hydrate and 0.15 gram of 5 percent palladium on carbon (approximately 60 percent wet). Over a period of two hours, the mixture was heated to 70° C., and held an additional ten hours at 70° C. The reduction was followed by high performance liquid chromatography by observing the disappearance of the starting tris-azo compound and the conversion of the intermediate di- and mono-azo compounds to the tris-amino compound and the formation of the by-product aniline. The title compound was isolated by filtration at 60° C. The filter cake was washed with 10 milliliters of isobutanol, dried to a constant weight to give 100 percent yield (2 grams) of 2,4,6-tris-[4-aminoanilino]-1,3,5-triazine. The melt point was 297°-299° C. The infrared spectrum was consistent with the structure. Relative area HPLC analysis showed it to be 97.8 percent pure. The filtrate was distilled to recover 1.1 grams of aniline, 78.6 percent of theory.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:14])[CH2:5][NH:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH3:2].C([O:17][C:18](=[O:24])[CH2:19][CH2:20][CH2:21][CH2:22]Br)C.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:7]([N:6]([CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:14])[CH2:22][CH2:21][CH2:20][CH2:19][C:18]([OH:24])=[O:17])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: CCOC(=O)CNCc1ccccc1
Reactant: CCOC(=O)CCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)CN(CCCCC(=O)O)Cc1ccccc1
Yield: 30 %

Procedure:
N-benzylglycine ethyl ester (1.87 ml) and 5-bromovaleric acid ethyl ester (1.92 ml) are dissolved in dimethylformamide (100 ml) and stirred in the presence of potassium carbonate (1.66 g) for 2 days at room temperature. The reaction is quenched with saturated aqueous ammonium chloride solution, and extraction is carried out with ethyl acetate. After drying over sodium sulphate the combined organic phases are concentrated by evaporation. From the obtained residue, 5-(benzyl-ethoxycarbonylmethyl-amino)-pentanoic acid is isolated in a yield of 30% by chromatography using silica gel (ethyl acetate/heptane 1:5).
Reaction SMILES: Br[C:2]1[CH:15]=[CH:14][C:13]2[C:4](=[CH:5][C:6]3[C:11]([CH:12]=2)=[CH:10][C:9](Br)=[CH:8][CH:7]=3)[CH:3]=1.C([Li])CCC.CCCCCC.[CH3:28][Si:29](Cl)([CH3:31])[CH3:30]>O.C1(C)C=CC=CC=1.O1CCCC1>[CH3:28][Si:29]([CH3:31])([CH3:30])[C:2]1[CH:15]=[CH:14][C:13]2[C:4](=[CH:5][C:6]3[C:11]([CH:12]=2)=[CH:10][C:9]([Si:29]([CH3:31])([CH3:30])[CH3:28])=[CH:8][CH:7]=3)[CH:3]=1
Reactant: Brc1ccc2cc3cc(Br)ccc3cc2c1
Reactant: C[Si](C)(C)Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: O
Product: C[Si](C)(C)c1ccc2cc3cc([Si](C)(C)C)ccc3cc2c1
Yield: 57 %

Procedure:
Under an atmospheric argon gas flow, 2,6-dibromoanthracene in an amount of 2.8 g (8.3 millimole), dried tetrahydrofuran (THF) in an amount of 200 milliliter and dried toluene in an amount of 200 milliliter were placed into a three necked-flask equipped with a cooling pipe and having a capacity of 1 liter and then, the resultant solution was cooled down to −30° C. Subsequently, n-butyllithium in an amount of 12 milliliter (19.1 millimole, 1.58 M hexane solution) was added slowly. Then, after adding trimethylsilylchloride in an amount of 2.4 milliliter (19.1 millimole, d=0.85) at a temperature of −70° C., the resultant solution was stirred at a room temperature for 1 hour. After completing the reaction, 100 milliliter of water was added and an organic layer was separated. The solution was dried with a use of sodium sulfate and then, the solvent was separated by distillation, and the residue was washed with a use of 100 milliliter of methanol and as a result, 1.7 g of pale yellow powder was obtained (the yield: 57%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2.[C:12](B1OC(C)(C)C(C)(C)O1)([CH3:14])=[CH2:13].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>CCCCO.O>[C:12]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2)([CH3:14])=[CH2:13]
Reactant: O=C1Cc2cc(Br)ccc2N1
Reactant: C=C(C)B1OC(C)(C)C(C)(C)O1
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCCCO
Product: C=C(C)c1ccc2c(c1)CC(=O)N2
Temperature: 110 °C
Yield: 46.2 %

Procedure:
A mixture of 5-bromoindolin-2-one (106 mg, 0.500 mmol), isopropenylboronic acid pinacol ester (0.14 mL, 0.750 mmol), K3PO4 (212 mg, 1.00 mmol), water (1 mL) and n-BuOH (4 mL) was briefly sonicated in a microwave vial and then purged with argon for 15 min. Tris(dibenzyldeneacetone)dipalladium (9.2 mg, 0.010 mmol) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (19 mg, 0.040 mmol) were added, the vial sealed and heated in microwave reactor at 110° C. for 1 hour. The solvent was removed and the residue purified by column chromatography (silica gel, 2:1, hexanes/EtOAc) to give 40 mg, 46% of 5-isopropenylindolin-2-one as a beige solid; 5-isopropenylindolin-2-one (15 mg, 0.0866 mmol) was then dissolved into MeOH and the solution purged with N2 (g). 2 mg of 10% Pd/C (Degussa type) was then added and the mixture purged briefly with H2 (g). The mixture was stirred under 1 atm of H2 (g) for 3 hours and then filtered through a pad of celite. The solvent was removed to give 15 mg, 99% of the product as an off-white solid. MS ESI 176.0 [M+H]+, calcd for [C11H13NO+H]+ 176.11.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[F:19])[CH2:5][NH:6][C:7](=[O:15])[CH2:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11].[CH2:20]([O:22][C:23](=[O:34])[C:24]1[CH:29]=[CH:28][C:27](F)=[C:26]([N+:31]([O-:33])=[O:32])[CH:25]=1)[CH3:21].C([O-])([O-])=O.[K+].[K+]>CS(C)=O.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[F:19])[CH2:5][NH:6][C:7](=[O:15])[CH:8]([C:27]1[CH:28]=[CH:29][C:24]([C:23]([O:22][CH2:20][CH3:21])=[O:34])=[CH:25][C:26]=1[N+:31]([O-:33])=[O:32])[C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11]
Reactant: CC(C)(C)C(=O)CC(=O)NCc1ccc(F)c(F)c1
Reactant: CCOC(=O)c1ccc(F)c([N+](=O)[O-])c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CCOC(=O)c1ccc(C(C(=O)NCc2ccc(F)c(F)c2)C(=O)C(C)(C)C)c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of N-(3,4-difluorobenzyl)-4,4-dimethyl-3-oxopentanamide (Compound 112, 126 mg, 0.47 mmol) and ethyl4-fluoro-3-nitrobenzoate (Compound 113, 100 mg, 0.47 mmol) in DMSO (1 ml) was added K2CO3 (130 mg, 0.94 mmol). The mixture was stirred at room temperature for 16 h, diluted with EtOAc, washed with 1 M HCl, H2O, and brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel (0→30% EtOAc-hexanes) to yield the title compound as a yellow solid.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([NH:11][C:12](=[O:25])[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)[CH:14]=2)[CH:7]=[CH:8][C:9]=1[CH3:10])([O-])=O.[H][H]>CO.[Pd]>[NH2:1][C:4]1[CH:5]=[C:6]([NH:11][C:12](=[O:25])[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([N:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)[CH:14]=2)[CH:7]=[CH:8][C:9]=1[CH3:10]
Reactant: Cc1ccc(NC(=O)c2cccc(N3CCOCC3)c2)cc1[N+](=O)[O-]
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: Cc1ccc(NC(=O)c2cccc(N3CCOCC3)c2)cc1N

Procedure:
10% Palladium-on-carbon (0.035 g) was added to a stirred solution in methanol (40 ml) of the nitro compound so obtained (0.28 g) and the mixture was stirred at ambient temperature under 1 atmosphere pressure of hydrogen. After uptake of hydrogen had ceased, the catalyst was removed by filtration and the filtrate was evaporated to give N-(3-amino-4-methylphenyl)-3-morpholinobenzamide; NMR Spectrum: (DMSOd6) 2.0 (s, 3H), 3.19 (t, 4H), 3.78 (t, 4H), 4.8 (s, 2H), 6.8 (q, 2H), 7.08 (s, 1H), 7.1 (d, 1H), 7.34 (m, 2H), 7.4 (s, 1H), 9.8 (s, 1H); Mass Spectrum: M+H+ 312.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]2[C:7]([CH2:10][C:11](O)=[O:12])=[CH:8][O:9][C:5]=2[CH:4]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]2[C:7]([CH2:10][CH2:11][OH:12])=[CH:8][O:9][C:5]=2[CH:4]=1
Reactant: COc1ccc2c(CC(=O)O)coc2c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1ccc2c(CCO)coc2c1
Reaction time: 1 h

Procedure:
A solution of (6-methoxy-benzofuran-3-yl)-acetic acid (10.16 g, 49.3 mmol) in 500 ml of THF is cooled in an ice-bath. To this solution is added LAH (1M in THF, 49.3 ml, 49.3 mmol) and stirring is continued for 1 hour. The reaction mixture is then poured onto ice cold 1N HCl and extracted 3-times with EtOAc. The combined organic layers are dried and evaporated.
Reaction SMILES: N([O-])=O.[Na+].N[C:6]1[CH:7]=[CH:8][C:9]2[C:10]3[N:11]([C:17](=[O:20])[NH:18][N:19]=3)[C:12](=[O:16])[NH:13][C:14]=2[CH:15]=1.[I-:21].[Na+]>C(O)(=O)C.S(=O)(=O)(O)O.O>[I:21][C:6]1[CH:7]=[CH:8][C:9]2[C:10]3[N:11]([C:17](=[O:20])[NH:18][N:19]=3)[C:12](=[O:16])[NH:13][C:14]=2[CH:15]=1
Reactant: [I-]
Reactant: Nc1ccc2c(c1)[nH]c(=O)n1c(=O)[nH]nc21
Agent: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: O=c1[nH]nc2c3ccc(I)cc3[nH]c(=O)n12
Temperature: 0 °C
Reaction time: 1 h
Yield: 53.3 %

Procedure:
63.8 mg (0.92 mmol) of sodium nitrite were added at 0° C. to a suspension of 210 mg (0.83 mmol) of 8-amino-2,3,5,6-tetrahydro-1,2,4-triazolo[4,3-c]quinazoline-3,5-dione in 10 ml of acetic acid and 10 ml of sulphuric acid. The reaction mixture was stirred at 0° C. for 1 hr. Subsequently, 2.49 g (16.6 mmol) of sodium iodide in 10 ml of water were added dropwise and the mixture was stirred at RT for a further 1 hr. The precipitate was filtered off, the brown crystals were suspended in 10 ml of 5% sodium thiosulphate solution, filtered off and dried in a vacuum. 145 mg (53%) of 8-iodo-2,3,5,6-tetrahydro-1,2,4-triazolo[4,3-c]quinazoline-3,5-dione were obtained as brownish crystals;