Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I.I.[N:3]1([C:10]2[N:14]([CH2:15][CH2:16][N:17]3[CH:21]=[CH:20][CH:19]=[N:18]3)[C:13]3[CH:22]=[CH:23][CH:24]=[CH:25][C:12]=3[N:11]=2)[CH2:9][CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH:38]=[N:37][N:36]=[N:35]2)=[CH:30][C:29]=1[C:39]([N:41]1[CH2:45][CH2:44][C@:43]([CH2:52][CH2:53]OS(C)(=O)=O)([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH2:42]1)=[O:40].C(N(C(C)C)CC)(C)C.C(#N)C>ClCCl>[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH:38]=[N:37][N:36]=[N:35]2)=[CH:30][C:29]=1[C:39]([N:41]1[CH2:45][CH2:44][C@@:43]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)([CH2:52][CH2:53][N:6]2[CH2:7][CH2:8][CH2:9][N:3]([C:10]3[N:14]([CH2:15][CH2:16][N:17]4[CH:21]=[CH:20][CH:19]=[N:18]4)[C:13]4[CH:22]=[CH:23][CH:24]=[CH:25][C:12]=4[N:11]=3)[CH2:4][CH2:5]2)[CH2:42]1)=[O:40]
Reactant: c1ccc2c(c1)nc(N1CCCNCC1)n2CCn1cccn1
Reactant: COc1ccc(-n2cnnn2)cc1C(=O)N1CC[C@](CCOS(C)(=O)=O)(c2ccccc2)C1
Agent: I
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Solvent: ClCCl
Product: COc1ccc(-n2cnnn2)cc1C(=O)N1CC[C@](CCN2CCCN(c3nc4ccccc4n3CCn3cccn3)CC2)(c2ccccc2)C1
Yield: 50.3 %

Procedure:
Reflux a mixture of 2-[1,4]diazepan-1-yl-1-(2-pyrazol-1-yl-ethyl)-1H-benzoimidazole dihydroiodide (0.48 g, 0.84 mmol), methanesulfonic acid 2-{(S)-1-[1-(2-methoxy-5-tetrazol-1-yl-phenyl)-methanoyl]-3-phenyl-pyrrolidin-3-yl}-ethyl ester (0.40 g, 0.84 mmol, example 47.2), diisopropylethylamine (0.44 g, 3.37 mmol) and acetonitrile (20 mL) for 12 hours. Cool and dilute with dichloromethane (150 mL), wash the organic phase with water (2×10 mL), dry (MgSO4) the organic phase, filter and evaporate. Purify the residue by silica gel chromatography eluting with 0.5% methanol in dichloromethane to afford 0.29 g of the title compound, Rf=0.18 (silica gel, 0.5% methanol in dichloromethane). The compound may be converted to the dihydrochloride salt by methods well known in the art.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[CH:8]([CH3:12])[CH2:7]2.[S:13]1[CH:17]=[CH:16][CH:15]=[C:14]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].O>C(COC)OC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1C1C=CC=CC=1P(C1C=CC=CC=1C1C=CC=CC=1C)C1C=CC=CC=1C1C=CC=CC=1C>[CH3:12][CH:8]1[CH2:7][C:6]2[C:10](=[C:2]([C:14]3[S:13][CH:17]=[CH:16][CH:15]=3)[CH:3]=[CH:4][CH:5]=2)[C:9]1=[O:11]
Reactant: CC1Cc2cccc(Br)c2C1=O
Reactant: OB(O)c1cccs1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1-c1ccccc1P(c1ccccc1-c1ccccc1C)c1ccccc1-c1ccccc1C
Solvent: COCCOC
Solvent: O
Product: CC1Cc2cccc(-c3cccs3)c2C1=O
Temperature: 80 °C
Reaction time: 2 h
Yield: 75.3 %

Procedure:
Using a method similar to Example 15a), 11.25 g (0.05 mol) of (2), 13.4 g (0.055 mol) of thiophenylboronic acid and 11.7 g (0.11 mol) of sodium carbonate were placed in 190 ml of dimethoxyethane and 60 ml of water in the reaction vessel, the mixture was degassed a number of times and saturated with argon. 225 mg (1 mmol) of palladium acetate and 0.609 g (2 mmol) of tris(o-tolylphenyl)phosphine were added and the reaction mixture was stirred for 2 hours at 80° C. After addition of 150 ml of water, the mixture was extracted 4 times with 100 ml each time of diethyl ether, the ether phase was washed twice with 50 ml each time of water and dried over magnesium sulfate. Removal of the solvent gave 8.6 g of (22) as an oil.
Reaction SMILES: [NH2:1][C:2]1[C:17]([O:18][CH3:19])=[CH:16][C:5]2[CH2:6][CH2:7][N:8]([CH2:11][C:12]([NH:14][CH3:15])=[O:13])[CH2:9][CH2:10][C:4]=2[CH:3]=1.Cl[C:21]1[N:26]=[C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([N:34]3[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]3)=[CH:30][C:29]=2[O:41][CH3:42])[C:24]([Cl:43])=[CH:23][N:22]=1>>[Cl:43][C:24]1[C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([N:34]3[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]3)=[CH:30][C:29]=2[O:41][CH3:42])=[N:26][C:21]([NH:1][C:2]2[C:17]([O:18][CH3:19])=[CH:16][C:5]3[CH2:6][CH2:7][N:8]([CH2:11][C:12]([NH:14][CH3:15])=[O:13])[CH2:9][CH2:10][C:4]=3[CH:3]=2)=[N:22][CH:23]=1
Reactant: CNC(=O)CN1CCc2cc(N)c(OC)cc2CC1
Reactant: COc1cc(N2CCN(C)CC2)ccc1Nc1nc(Cl)ncc1Cl
Product: CNC(=O)CN1CCc2cc(Nc3ncc(Cl)c(Nc4ccc(N5CCN(C)CC5)cc4OC)n3)c(OC)cc2CC1

Procedure:
The title compound was prepared from 2-(7-Amino-8-methoxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-N-methyl-acetamide and (2,5-Dichloro-pyrimidin-4-yl)-[2-methoxy-4-(4-methyl-piperazin-1-yl)-phenyl]-amine in an analogous manner to Example 61e. Product isolated as an off-white solid (0.005 g, 10%). MP: 82-100° C. 1HNMR (400 MHz, CDCl3, δ, ppm): 8.20 (d, 1H, J=8.8 Hz), 8.12 (s, 1H), 8.02 (s, 1H), 7.50 (s, 1H), 7.44 (s, 1H), 7.39-7.31 (m, 1H), 6.63 (s, 1H), 6.56 (d, 1H), J=2.0 Hz), 6.50 (dd, 1H, J=8.7 and 2.4 Hz), 3.91 (s, 3H), 3.86 (s, 3H), 3.23-3.16 (m, 4H), 3.11 (s, 2H), 2.90 (d, 3H, J=5.1 Hz), 2.88-2.83 (m, 2H), 2.83-2.78 (m, 2H), 2.72-2.65 (m, 4H), 2.65-2.58 (m, 4H), 2.38 (s, 3H). MS: 595 (MH)+.
Reaction SMILES: [N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Br[C:15]1[C:23]2[O:22][CH2:21][O:20][C:19]=2[CH:18]=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[O:20]1[C:19]2[CH:18]=[CH:17][CH:16]=[C:15]([N:4]3[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]3)[C:23]=2[O:22][CH2:21]1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: Brc1cccc2c1OCO2
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Solvent: O
Product: CC(C)(C)OC(=O)N1CCN(c2cccc3c2OCO3)CC1
Temperature: 100 °C
Yield: 75.5 %

Procedure:
Tert-butyl piperazine-1-carboxylate (1.11 g, 5.97 mmol) was added to a solution of 4-bromobenzo[d][1,3]dioxole (1 g, 4.97 mmol) in Toluene (15.0 ml). The resulting suspension was degassed using a stream of argon. Cesium carbonate (2.27 g, 558 μl, 6.96 mmol), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphtyl (232 mg, 373 μmol, Eq: 0.075) and Palladium (II) Acetate (55.8 mg, 249 μmol) were added to this mixture. The reaction was then heated at 100° C. over night. The reaction was cooled to rt, 40 ml of water was added and the mixture was extracted with Ethyl Acetate (2×80 ml). The organic layers were dried over MgSO4 and concentrated under vacuum. The crude material was purified by flash chromatography (silica gel, 50 g, 0% to 50% EtOAc in heptane). to yield tert-butyl 4-(benzo[d][1,3]dioxol-4-yl)piperazine-1-carboxylate as a white solid (1.15 g, 75%). MS (ISP) m/z=307.4 [(M+H)+].
Reaction SMILES: [NH2:1][C@H:2]1[CH2:8][CH2:7][CH2:6][CH2:5][N:4]([CH2:9][C:10]([OH:12])=[O:11])[C:3]1=[O:13].[NH:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]([CH2:23][CH2:24][C:25](=O)[C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:15]1>>[C:10]([CH2:9][N:4]1[CH2:5][CH2:6][CH2:7][CH2:8][C@H:2]([NH:1][CH:25]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:24][CH2:23][C:16]2[C:17]3[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=3)[NH:14][CH:15]=2)[C:3]1=[O:13])([OH:12])=[O:11]
Reactant: N[C@H]1CCCCN(CC(=O)O)C1=O
Reactant: CCOC(=O)C(=O)CCc1c[nH]c2ccccc12
Product: CCOC(=O)C(CCc1c[nH]c2ccccc12)N[C@H]1CCCCN(CC(=O)O)C1=O

Procedure:
In the same manner react the 3-(S)-amino-1-carboxymethylperhydroazepin-2-one with ethyl 4-(3-indolyl)-2-oxobutyrate to obtain 1-carboxymethyl-3-(S)-[(1-ethoxycarbonyl-3-(3-indolyl)propyl)amino]perhydroazepin-2-one. Standard alkaline hydrolysis (as in Example 3) of this material yields 1-carboxymethyl-3-(s)-[(1-carboxy-3-(3-indolyl)propyl)amino]perhydroazepin-2-one. Alternatively, esterification in HCl-ethanol affords 1-ethoxycarbonylmethyl-3-(S)-1-(1-ethoxycarbonyl-3-(3-indolyl)lpropyl)amino]-perhydroazepin-2-one.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4](Cl)=[O:5].C(N(CC)CC)C.[NH2:19][C:20]1[CH:41]=[CH:40][C:23]([C:24]([N:26]2[C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=3[CH2:30][N:29]3[CH:37]=[CH:38][CH:39]=[C:28]3[CH2:27]2)=[O:25])=[CH:22][CH:21]=1>C(Cl)Cl.C(OCC)(=O)C>[CH:39]1[CH:38]=[CH:37][N:29]2[CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[N:26]([C:24]([C:23]3[CH:22]=[CH:21][C:20]([NH:19][C:4](=[O:5])[C:3]4[CH:7]=[C:8]([Cl:11])[CH:9]=[CH:10][C:2]=4[Cl:1])=[CH:41][CH:40]=3)=[O:25])[CH2:27][C:28]=12
Reactant: Nc1ccc(C(=O)N2Cc3cccn3Cc3ccccc32)cc1
Reactant: O=C(Cl)c1cc(Cl)ccc1Cl
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: O=C(Nc1ccc(C(=O)N2Cc3cccn3Cc3ccccc32)cc1)c1cc(Cl)ccc1Cl
Temperature: 25 °C
Reaction time: 3 h
Yield: 35 %

Procedure:
To a solution of 414.5 mg of 2,5-dichlorobenzoyl chloride in 5 ml of methylene chloride is added 276 μl of triethylamine. After stirring at 0° C. for 3 minutes 400 mg of the 10,11-dihydro-10-(4-aminobenzoyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine is added. The bath is removed and the reaction mixture stirred at room temperature for 3 hours. The volatiles are concentrated in vacuo to give a residue which is dissolved in ethyl acetate and washed with water, 2N citric acid, 1M NaHCO and brine. The organic layer is dried with Na2 SO4 and concentrated in vacuo to a residue which is purified by thick layer chromatography by elution with 1:1 ethyl acetate-hexanes to give a residue. The residue is crystallized from ethyl acetate to give 220 mg of the desired product as white crystals, m.p. 218°-220° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][CH:10]([C:13]3[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][CH:14]=3)[N:9]2[C:20]2[CH:25]=[CH:24][C:23](I)=[CH:22][CH:21]=2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:35]2[CH:36]=[CH:37][C:38]([N:41]3[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)=[N:39][CH:40]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][CH:10]([C:13]3[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][CH:14]=3)[N:9]2[C:20]2[CH:25]=[CH:24][C:23]([C:35]3[CH:36]=[CH:37][C:38]([N:41]4[CH2:42][CH2:43][O:44][CH2:45][CH2:46]4)=[N:39][CH:40]=3)=[CH:22][CH:21]=2)=[CH:4][CH:3]=1
Reactant: CC1(C)OB(c2ccc(N3CCOCC3)nc2)OC1(C)C
Reactant: Brc1ccc(C2CCC(c3ccc(Br)cc3)N2c2ccc(I)cc2)cc1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: O=P([O-])([O-])[O-]
Solvent: C1CCOC1
Solvent: O
Product: Brc1ccc(C2CCC(c3ccc(Br)cc3)N2c2ccc(-c3ccc(N4CCOCC4)nc3)cc2)cc1

Procedure:
The product from Example 185A (0.1 g, 0.171 mmol), 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)morpholine (0.050 g, 0.171 mmol), potassium phosphate (0.028 mL, 0.343 mmol), tris(dibenzylideneacetone)dipalladium(0) (1.570 mg, 1.715 μmol) and 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamante (1.504 mg, 5.14 μmol) were combined in THF (1.2 mL)/water (0.4 mL). The mixture was sparged with nitrogen for 15 minutes diluted into EtOAc, washed with 1M sodium bicarbonate, brine, dried (Na2SO4), filtered and concentrated. Purification by flash chromatography on an Isco 12 g silica cartridge eluting with 20-70% EtOAc in hexane gave the title compound as a cream colored powder (91 mg, 86%). %). MS (ESI) m/z 620 (M+H)+.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N+:20]([C:23]1[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=1)([O-:22])=[O:21].C(OC(N=NC(OC(C)C)=O)=O)(C)C.[CH3:46][O:47][C:48]1[CH:65]=[CH:64][C:63]2[C@@H:62]3[C@H:53]([C@H:54]4[C@@:58]([CH2:60][CH2:61]3)([CH3:59])[C@@H:57](O)[CH:56]=[CH:55]4)[CH2:52][CH2:51][C:50]=2[CH:49]=1.[Cl-].[Na+]>O1CCCC1>[CH3:46][O:47][C:48]1[CH:65]=[CH:64][C:63]2[C@@H:62]3[C@H:53]([C@H:54]4[C@@:58]([CH2:60][CH2:61]3)([CH3:59])[CH:57]([O:28][C:27](=[O:29])[C:26]3[CH:25]=[CH:24][C:23]([N+:20]([O-:22])=[O:21])=[CH:31][CH:30]=3)[CH:56]=[CH:55]4)[CH2:52][CH2:51][C:50]=2[CH:49]=1
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Reactant: COc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](O)C=C[C@@H]12
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: [Cl-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)C(OC(=O)c3ccc([N+](=O)[O-])cc3)C=C[C@@H]12
Temperature: 23 °C
Reaction time: 2 h
Yield: 78.5 %

Procedure:
121 g triphenylphosphine, 27.1 g 4-nitrobenzoic acid, and 30.9 ml azodicarboxylic acid diisopropyl ester are added to a solution of 43.9 g of 3-methoxy-17β-hydroxyestra-1,3,5(10),15-tetraene in 1.6 l tetrahydrofuran and it is stirred for 23° C. for 2 hours. Saturated sodium chloride solution is added, it is extracted with ethyl acetate, the combined organic extracts are washed with saturated sodium chloride solution and dried over sodium sulfate. The residue obtained after filtration and evaporation of the solvent is taken up in 1.2 l acetone, 80 ml of 30% hydrogen peroxide solution is added while cooling, and after 20 minutes it is poured, while cooling, into 600 ml of semiconcentrated sodium thiosulfate solution. It is extracted with ethyl acetate, the combined organic extracts are washed with saturated sodium chloride solution and dried over sodium sulfate. The residue obtained after filtration and evaporation of the solvent is purified by recrystallization. 52.5 g of the title compound is isolated.
Reaction SMILES: [CH2:1]([Li])[CH2:2][CH2:3][CH3:4].C(NC(C)C)(C)C.[CH:13]1([C:19]([OH:21])=[O:20])[CH2:18][CH2:17][CH2:16]CC1.BrCC#CC.Cl>CCCCCC.O1CCCC1>[CH3:4][C:3]#[C:2][CH2:1][C:13]1([C:19]([OH:21])=[O:20])[CH2:16][CH2:17][CH2:18]1
Reactant: [Li]CCCC
Reactant: O=C(O)C1CCCCC1
Agent: CC#CCBr
Agent: Cl
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CC#CCC1(C(=O)O)CCC1
Temperature: -10 °C
Reaction time: 0.5 h

Procedure:
At -30° C., 265 ml of 1.66-molar butyllithium solution in hexane is added to a solution of 44.52 g of diisopropylamine in 200 ml of tetrahydrofuran, and thereafter 20.02 g of cyclohexanecarboxylic acid is added thereto. The mixture is stirred for 30 minutes at -10° C. and then 31.92 g of 1-bromo-2-butyne is added dropwise and the mixture is agitated for 16 hours at 25° C. whereupon it is poured on 600 ml of ice water. After acidifying with 2N hydrochloric acid to pH 4, the mixture is extracted with ether, the extract is washed with brine, dried over magnesium sulfate, and the the evaporated under vacuum. The residue is purified by distillation, thus obtaining 18 g of 2,2-trimethylenehex-4-ynoic acid (bp 140° C.-143° C., 15 torr).
Reaction SMILES: [NH2:1][C@@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][C:13]([F:16])([F:15])[F:14])[CH:10]=2)[O:5][C:4]([CH3:18])([CH3:17])[C@H:3]1[OH:19].C(N(CC)CC)C.[N+:27]([C:30]1[CH:38]=[CH:37][CH:36]=[CH:35][C:31]=1[C:32](Cl)=[O:33])([O-:29])=[O:28].C(N)(=O)C1C=CC=CC=1>ClCCl>[OH:19][C@H:3]1[C@H:2]([NH:1][C:32](=[O:33])[C:31]2[CH:35]=[CH:36][CH:37]=[CH:38][C:30]=2[N+:27]([O-:29])=[O:28])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][C:13]([F:16])([F:14])[F:15])[CH:10]=2)[O:5][C:4]1([CH3:17])[CH3:18]
Reactant: CC1(C)Oc2ccc(OC(F)(F)F)cc2[C@@H](N)[C@@H]1O
Reactant: O=C(Cl)c1ccccc1[N+](=O)[O-]
Agent: NC(=O)c1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC1(C)Oc2ccc(OC(F)(F)F)cc2[C@@H](NC(=O)c2ccccc2[N+](=O)[O-])[C@@H]1O
Temperature: 15 °C
Yield: 47 %

Procedure:
(3S,4R)-4-Amino-2,2-dimethyl-6-(trifluoromethoxy)-chroman-3-ol [prepared by the method of Quagliato et al. Biorg. & Med. Chem. Let. 1991 1, 39; (2.75 g, 10 mmol)] and triethylamine (1.39 mL, 10 mmol) were stirred together in dichloromethane (25 mL) at 0° C. To this solution was added a solution of 2-nitrobenzoylchloride (1.32 mL, 10 mmol) in dichloromethane (10 mL). The ice bath was allowed to gradually warm to 15° C. overnight. The crude benzamide was diluted with dichloromethane (50 mL), washed with water (2×10 mL), dried (MgSO4) and concentrated to afford 2.0 g (47%) of white solid: m.p. 189°-190° C.; 1H NMR (DMSO-d6): δ 9.17 (d, 1H), 8.04 (d, 1H), 7.81 (m, 2H), 7.71 (t, 1H), 7.33 (s, 1H), 7.16 (d, 1H), 6.86 (d, 1H), 5.86 (d, 1H), 4.96 (br t, 1H), 3.64 (dd, 1H), 1.42 (s, 3H), 1.19 (s, 3H).
Reaction SMILES: S(=O)(=O)(O)O.Br[C:7]1[CH:24]=[CH:23][C:22]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]=2[CH:8]=1.[C:25]1([NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(=O)([O-])[O-].[K+].[K+]>[Cu].O>[C:32]1([N:31]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:7]2[CH:24]=[CH:23][C:22]3[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[C:15]4[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=4)[C:9]=3[CH:8]=2)[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1
Reactant: c1ccc(Nc2ccccc2)cc1
Reactant: Brc1ccc2c3ccccc3c3ccccc3c2c1
Agent: [Cu]
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Solvent: O
Product: c1ccc(N(c2ccccc2)c2ccc3c4ccccc4c4ccccc4c3c2)cc1
Temperature: 60 °C
Reaction time: 5 h

Procedure:
Triphenylene and N-bromosuccinimide were introduced to mixture (4:1) of water and sulfuric acid and stirred for five hours at 60° C. The object compound was extracted from the reacted solution using toluene and neutralized with 5% sodium hydrogencarbonate solution. After drying the compound by using magnesium sulfate, coarse crystals of the compound, left after evaporation of the solvent, were recrystallized from the toluene-hexane mixed solvent, to prepare 2-bromotriphenylene compound. Thereafter, the 2-bromotriphenylene compound, diphenylamine, potassium carbonate and copper powder were introduced in a three-necked flask, and stirred for 30 hours at 200° C. The reaction product was subjected to extraction using toluene and to washing using water. Then, the product was subjected to drying using magnesium sulfate, evaporation of the solvent, and separation refinement by silica gel column chromatography using a 1:2 mixture of toluene and hexane to obtain 2-diphenylaminotriphenylene.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[C:8]([N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][S:11]2(=[O:17])=[O:16])[CH:7]=[C:6](Br)[CH:5]=1.[CH:20]([O:22]CCCC)=[CH2:21].C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[K+].[K+].Cl>CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[C:8]([N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][S:11]2(=[O:17])=[O:16])[CH:7]=[C:6]([C:20](=[O:22])[CH3:21])[CH:5]=1
Reactant: COC(=O)c1cc(Br)cc(N2CCCCS2(=O)=O)c1
Reactant: C=COCCCC
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cl
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1cc(C(C)=O)cc(N2CCCCS2(=O)=O)c1
Temperature: 122 °C
Yield: 44.6 %

Procedure:
A mixture of 3-bromo-5-(1,1-dioxo-1λ6-[1,2]thiazinan-2-yl)-benzoic acid methyl ester (500 mg, 1.44 mmol), 1-(vinyloxy)butane (288.6 mg, 0.37 mL, 2.88 mmol), palladium acetate (9.6 mg, 0.043 mmol), DPPP (39.2 mg, 0.095 mmol) and potassium carbonate (238.5 mg, 1.73 mmol) in DMF (3.8 mL) and H2O (0.45 mL) in a Smith process vial was heated at 122° C. in microwave for 3 h. The reaction mixture was cooled down to room temperature and hydrolyzed by addition of 5% HCl (6 mL) slowly. The reaction mixture was worked up by extraction with ethyl acetate and concentration under vacuum. The crude mixture was purified by reverse phase prep HPLC to give the title compound (200 mg): 1H NMR (CD3OD, 500 MHz) δ ppm 1.93-2.01 (2H, m), 2.31-2.37 (2H, m), 2.67 (3H, s), 3.27-3.30 (2H, m), 3.83 (2H, t, J=5 Hz), 3.98 (3H, s), 8.14 (1H, m), 8.19 (1H, m), 8.51 (1H, m). HPLC retention time: 1.448 min (method A). MS (ESI) (M+H)+ 312.13.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[S:10][CH2:11][C:12]([N:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17][CH2:16][CH2:15]1)=[O:13].C1C=C(Cl)C=C(C(OO)=[O:32])C=1>C(Cl)Cl>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[S:10]([CH2:11][C:12]([N:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17][CH2:16][CH2:15]1)=[O:13])=[O:32]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: O=C(CSc1nc2ccccc2s1)N1CCCc2ccccc21
Solvent: ClCCl
Product: O=C(CS(=O)c1nc2ccccc2s1)N1CCCc2ccccc21
Reaction time: 1 h
Yield: 93.9 %

Procedure:
To a solution of compound 64 (167 mg, 0.49 mmol) in DCM (4 mL) cooled in a salt-ice bath was added a solution of mCPBA (77%, 110 mg, 0.49 mmol) in DCM (4 mL) drop wise. The reaction mixture was stirred for 1 hr. After diluting with DCM (30 mL), the solution washed with Na2S2O3, NaHCO3, dried over Na2SO4 and concentrated in vacuum. The crude material was purified by flash chromatography on silica gel eluting with EtOAc/hexanes (20˜50%) to give compound 65 as a white solid (164 mg, 94%). MS (APCI): m/z 357 [M+H]+. Anal. Calcd for C18H16N2O2S2: C, 60.65; H, 4.52; N, 7.86. Found: C, 60.44; H, 4.66; N, 7.73.
Reaction SMILES: Br[C:2]1[C:3]([O:27][C:28]2[C:29]([CH3:34])=[N:30][CH:31]=[CH:32][CH:33]=2)=[CH:4][C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[N:13]=2)=[N:6][CH:7]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:85][O:86][C:87]1[CH:88]=[C:89]([SH:93])[CH:90]=[CH:91][CH:92]=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:85][O:86][C:87]1[CH:88]=[C:89]([S:93][C:2]2[C:3]([O:27][C:28]3[C:29]([CH3:34])=[N:30][CH:31]=[CH:32][CH:33]=3)=[CH:4][C:5]([NH:8][C:9]3[S:10][CH:11]=[C:12]([CH:14]4[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]4)[N:13]=3)=[N:6][CH:7]=2)[CH:90]=[CH:91][CH:92]=1
Reactant: COc1cccc(S)c1
Reactant: Cc1ncccc1Oc1cc(Nc2nc(C3CCN(C(=O)OC(C)(C)C)CC3)cs2)ncc1Br
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: Cc1ccccc1
Product: COc1cccc(Sc2cnc(Nc3nc(C4CCN(C(=O)OC(C)(C)C)CC4)cs3)cc2Oc2cccnc2C)c1
Temperature: 130 °C
Reaction time: 3 h
Yield: 51.4 %

Procedure:
tert-Butyl 4-(2-(5-bromo-4-(2-methylpyridin-3-yloxy)pyridin-2-ylamino)thiazol-4-yl)piperidine-1-carboxylate (0.15 g, 0.27 mmol), Pd2dba3 (0.25 g, 0.27 mmol), Xantphos (0.20 g, 0.34 mmol), and K3PO4 (0.175 g, 0.823 mmol) were suspended in degassed toluene (2 mL). 3-Methoxybenzenethiol (0.068 mL, 0.55 mmol) was added. The mixture was stirred at 130° C. for 3 hours in a sealed tube. The solution was cooled and flash chromatographed (40-50% EtOAc/hexanes) to afford the title compound (0.084 g, 51% yield) as an off-white solid.