Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]=[C:12]=[O:13])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH2:14][C:15]1[C:23]([CH3:24])=[CH:22][CH:21]=[CH:20][C:16]=1[C:17](O)=[O:18]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([N:11]2[C:17](=[O:18])[C:16]3[C:15](=[C:23]([CH3:24])[CH:22]=[CH:21][CH:20]=3)[NH:14][C:12]2=[O:13])(=[O:9])=[O:10])=[CH:6][CH:7]=1
Reactant: O=C=NS(=O)(=O)c1ccc(Cl)cc1
Reactant: Cc1cccc(C(=O)O)c1N
Product: Cc1cccc2c(=O)n(S(=O)(=O)c3ccc(Cl)cc3)c(=O)[nH]c12
Yield: 97.9 %

Procedure:
2.00 g (9.19 mmol) of 4-chlorobenzenesulfonylisocyanate and 1.26 g (8.33 mmol) of 2-amino-3-methylbenzoic acid were treated in the same way as in Example 1 to obtain 2.86 g of the above-identified compound (yield 98.0%). Properties: colorless crystal, Melting point: 221°-225° C., PMR (δppm, DMSO-d6): 2.32 (3H,s), 7.12 (1H,t), 7.51 (1H,d), 7.72 (1H,d), 7.76 (2H,d), 8.19 (2H,d), 11.10 (1H,br).
Reaction SMILES: C[O:2][C:3]([C:5]1[N:6]=[C:7]([C@@H:22]2[CH2:26][C:25]([F:28])([F:27])[CH2:24][N:23]2[C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:30])[N:8]([CH3:21])[C:9](=[O:20])[C:10]=1[O:11]C(=O)C1C=CC=CC=1)=O.[F:39][C:40]1[CH:47]=[CH:46][C:43]([CH2:44][NH2:45])=[CH:42][CH:41]=1>CO>[CH2:32]([O:31][C:29]([N:23]1[CH2:24][C:25]([F:28])([F:27])[CH2:26][C@H:22]1[C:7]1[N:8]([CH3:21])[C:9](=[O:20])[C:10]([OH:11])=[C:5]([C:3]([NH:45][CH2:44][C:43]2[CH:46]=[CH:47][C:40]([F:39])=[CH:41][CH:42]=2)=[O:2])[N:6]=1)=[O:30])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: NCc1ccc(F)cc1
Reactant: COC(=O)c1nc([C@@H]2CC(F)(F)CN2C(=O)OCc2ccccc2)n(C)c(=O)c1OC(=O)c1ccccc1
Solvent: CO
Product: Cn1c([C@@H]2CC(F)(F)CN2C(=O)OCc2ccccc2)nc(C(=O)NCc2ccc(F)cc2)c(O)c1=O

Procedure:
Methyl-5-(benzoyloxy)-2-{(2S)-1-[(benzyloxy)carbonyl]-4,4-difluoropyrrolidin-2-yl}-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylate in dry MeOH was treated with 4-fluorobenzyl amine (2.5 eq.) at reflux for 2 hours. Solvent was removed in vacuo and the residue was taken up in ethyl acetate, washed with HCl 1N, brine, dried over Na2SO4. The filtrate was concentrated in vacuo and triturated with ethyl ether to obtain the title compound as a 1.5:1 mixture of two rotamers by NMR.
Reaction SMILES: [NH2:1][CH:2]1[C:25](=[O:26])[N:4]2[C:5]([C:22]([OH:24])=[O:23])=[C:6]([CH:9]([S:16][C:17]3[NH:21][N:20]=[N:19][N:18]=3)[CH2:10][CH2:11][S:12](=[O:15])(=[O:14])[NH2:13])[CH2:7][S:8][C@H:3]12.C(=O)(O)[O-].[Na+].[CH3:32][CH2:33][C:34](Cl)=[S:35].[OH-].[Na+]>CC(C)=O>[CH3:32][CH2:33][C:34]([NH:1][CH:2]1[C:25](=[O:26])[N:4]2[C:5]([C:22]([OH:24])=[O:23])=[C:6]([CH:9]([S:16][C:17]3[NH:18][N:19]=[N:20][N:21]=3)[CH2:10][CH2:11][S:12](=[O:14])(=[O:15])[NH2:13])[CH2:7][S:8][C@H:3]12)=[S:35]
Reactant: CCC(=S)Cl
Reactant: NC1C(=O)N2C(C(=O)O)=C(C(CCS(N)(=O)=O)Sc3nnn[nH]3)CS[C@H]12
Agent: O=C([O-])O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Product: CCC(=S)NC1C(=O)N2C(C(=O)O)=C(C(CCS(N)(=O)=O)Sc3nnn[nH]3)CS[C@H]12
Reaction time: 0.33 h

Procedure:
To a stirred, cooled (-20°) solution of 10.8 g. (0.026 mol.) of 7-amino-3-[1-(2-sulfamoylethyl)tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid in 220 ml. of 3% sodium bicarbonate and 220 ml. of acetone is dropwise added a solution of 3.66 g. (0.029 mol.) of methylthioacetyl chloride in 52 ml. of acetone, during which time the pH of the reaction mixture is maintained at 8.0 by addition of 10% sodium hydroxide. After addition the reaction mixture is stirred an additional 20 minutes at -15°, then is warmed to 25° and extracted with ether. The remaining aqueous phase is cooled, 250 ml. of ethyl acetate is added and the slurry is acidified with 3N hydrochloric acid. The layers are separated and the aqueous phase is extracted twice more with ethyl acetate. The combined extracts are dried (MgSO4) and evaporated to dryness to yield the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][OH:10])[CH:5]=[C:4]([Br:11])[C:3]=1[OH:12].CC(C)([O-])C.[K+].[Cl:19][C:20]1[N:21]=[N:22][C:23](Cl)=[CH:24][C:25]=1[CH:26]([CH3:28])[CH3:27]>CN(C)C(=O)C.O>[Br:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][OH:10])[CH:5]=[C:4]([Br:11])[C:3]=1[O:12][C:23]1[N:22]=[N:21][C:20]([Cl:19])=[C:25]([CH:26]([CH3:28])[CH3:27])[CH:24]=1
Reactant: CC(C)c1cc(Cl)nnc1Cl
Reactant: OCCc1cc(Br)c(O)c(Br)c1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: CC(C)c1cc(Oc2c(Br)cc(CCO)cc2Br)nnc1Cl
Temperature: 100 °C
Yield: 49.7 %

Procedure:
A mixture of 2,6-dibromo-4-(2-hydroxy-ethyl)-phenol (11) (183.3 g, 0.619 mol) in N,N-dimethyl acetamide (300 mL) was treated with potassium tert-butoxide (70.5 g, 0.59 mol) under nitrogen at room temperature. The suspension was heated to 100° C. and stirred until a solution formed. At this time, 3,6-dichloro-4-isopropyl pyridazine (7) (100 g, 0.50 mol) was added to the solution and the reaction mixture was stirred at 135° C. for 24 h. The reaction was cooled to room temperature, diluted with water (350 mL) and extracted with tert-butyl methyl ether (1×600 mL) followed by isopropyl acetate (1×600 mL). The organic layers were combined and washed with a 1N aqueous sodium hydroxide solution (1×256 mL) and water (2×200 mL). The organic layer was distilled to about 300 mL. The residue was treated with heptane (300 mL). The mixture was stirred under reflux for 30 min and then was cooled to room temperature. The resulting solid was filtered, washed with a 2:1 mixture of tert-butyl methyl ether: heptane (240 mL) and dried overnight to afford 2-[3,5-dibromo-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-phenyl]-ethanol (12) (112 g, 49%) as an off-white solid; LRMS for C15H15Br2ClN2O2 (M+) at m/z=450. Molecular Weight=450.5600; Exact Mass=447.9189
Reaction SMILES: [CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[CH:19][N:20]4[C:25]=3[C:24]([NH2:26])=[N:23][C:22]([CH3:27])=[N:21]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:28]N1C(C)(C)C(=O)N(Br)C1=O>ClCCl>[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19]([Br:28])[N:20]4[C:25]=3[C:24]([NH2:26])=[N:23][C:22]([CH3:27])=[N:21]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1nc(N)c2c(-c3ccc4cn(Cc5ccccc5)nc4c3)ccn2n1
Reactant: CC1(C)C(=O)N(Br)C(=O)N1Br
Solvent: ClCCl
Product: Cc1nc(N)c2c(-c3ccc4cn(Cc5ccccc5)nc4c3)cc(Br)n2n1
Reaction time: 0.58 h
Yield: 186.6 %

Procedure:
A stirred solution of 5-(2-benzyl-2H-indazol-6-yl)-2-methylpyrrolo[2,1-f][1,2,4]triazin-4-amine (130 mg, 0.367 mmol) in dichloromethane (10 mL) was cooled (−30° C.) under nitrogen atmosphere, and a solution of 1,3-dibromo-5,5-dimethyl-imidazolidine-2,4-dione (52.4 mg, 0.183 mmol) in dichloromethane (10 mL) was added dropwise. After 35 min, the mixture was concentrated in vacuo and purified via MPLC (hexanes/ethyl acetate gradient) to afford 148 mg (93%) of sand-colored solid. 1H-NMR (CD2Cl2): δ 8.04 (d, 1 H), 7.77 (dd, 1 H), 7.73 (dd, 1 H), 7.40-7.31 (m, 5 H), 7.18 (dd, 1 H), 6.75 (s, 1 H), 5.61 (s, 2 H), 5.52 (br s, 2 H), 2.41 (s, 3 H). MS: LC/MS (+esi), m/z=433 [M+H]. RT=2.88 min.
Reaction SMILES: COC[O:4][C:5]1[CH:6]=[C:7](B(O)O)[CH:8]=[CH:9][CH:10]=1.I[C:15]1[CH:25]=[CH:24][C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC>[OH:4][C:5]1[CH:6]=[C:7]([C:15]2[CH:25]=[CH:24][C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:17][CH:16]=2)[CH:8]=[CH:9][CH:10]=1
Reactant: CCOC(=O)c1ccc(I)cc1
Reactant: COCOc1cccc(B(O)O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: COCCOC
Product: CCOC(=O)c1ccc(-c2cccc(O)c2)cc1
Temperature: 90 °C

Procedure:
2 g of 3-methoxymethoxyphenylboronic acid (13.3 mmol) and 1.86 mL (11 mmol) of ethyl 4-iodobenzoate are dissolved in 20 mL of DME. 13.3 mL of 2M potassium carbonate solution (26.6 mmol) are then added and the reaction medium is degassed with a stream of argon for 10 minutes. 640 mg of Pd(PPh3)4 are then added and the mixture is heated at 90° C. for 14 hours. After treatment with saturated ammonium chloride solution, extraction with ethyl acetate and then drying and evaporation of the solvents from the organic phase, the residue is dissolved in 25 mL of anhydrous methanol and 0.5 mL of sulphuric acid is then added; The reaction medium is refluxed for 15 h and then cooled and finally treated by addition of water. After extraction with ethyl acetate, the organic phase is separated out by settling, dried and then concentrated under reduced pressure. After purification by chromatography on a column of silica, a colourless oil is obtained (m=2 g; Y=75%). (
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:15]2[C:23]3[C:18](=[C:19]([CH2:25][S:26][CH3:27])[CH:20]=[C:21]([F:24])[CH:22]=3)[NH:17][CH:16]=2)[CH2:9][C:10](OCC)=[O:11])=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:15]2[C:23]3[C:18](=[C:19]([CH2:25][S:26][CH3:27])[CH:20]=[C:21]([F:24])[CH:22]=3)[NH:17][CH:16]=2)[CH2:9][CH2:10][OH:11])=[CH:6][CH:7]=1
Reactant: CCOC(=O)CC(c1ccc(Cl)cc1)c1c[nH]c2c(CSC)cc(F)cc12
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: C1CCOC1
Product: CSCc1cc(F)cc2c(C(CCO)c3ccc(Cl)cc3)c[nH]c12
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A solution of 1.29 g of the compound from Example 40A with a purity of 79% (2.52 mmol) in 30 ml of tetrahydrofuran was added dropwise to 11.1 ml (11.1 mmol) of a 1N solution of lithium aluminum hydride in tetrahydrofuran in 70 ml of tetrahydrofuran at RT under argon. The mixture was stirred at RT for 15 min and then 1N hydrochloric acid was added. The mixture was extracted with dichloromethane, and the organic phase was dried over magnesium sulfate, filtered and concentrated. The crude product was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid) to result in 0.68 g (74% of theory) of the title compound.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[OH:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][CH:17]([O:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:12][CH:11]=1>C(Cl)(Cl)Cl>[Br:1][C:15]1[CH:14]=[C:13]([CH2:16][CH:17]([O:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:12]=[CH:11][C:10]=1[OH:9]
Reactant: CCOC(=O)C(Cc1ccc(O)cc1)Oc1ccccc1
Reactant: O=C1CCC(=O)N1Br
Solvent: ClC(Cl)Cl
Product: CCOC(=O)C(Cc1ccc(O)c(Br)c1)Oc1ccccc1
Temperature: 70 °C
Reaction time: 4 h
Yield: 77.3 %

Procedure:
N-bromosuccinimide (1.12 g) was added to a solution of ethyl 3-(4-hydroxyphenyl)-2-phenoxypropionate (1.43 g), which is the product of reference example 4(c) in chloroform (20 ml) at ambient temperature. The mixture was stirred at 70° C. for 4 hour and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The ethyl acetate layer was separated and washed with saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified via chromatography on silica gel column using hexane/ethyl acetate=4/1 as the eluant to afford the desired compound (1.41 g) as a colorless oil.
Reaction SMILES: [O:1]=[C:2]1[N:6]([CH2:7][C:8]2[C:13]([C:14]([F:17])([F:16])[F:15])=[CH:12][CH:11]=[CH:10][C:9]=2[O:18][CH3:19])[C@@H:5]([C:20]([OH:22])=O)[CH2:4][CH2:3]1.[NH2:23][CH:24]([CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH:25]([OH:29])[C:26]([NH2:28])=[O:27].O[NH-].O=[N-]>>[NH2:28][C:26](=[O:27])[C:25](=[O:29])[CH:24]([NH:23][C:20]([C@H:5]1[CH2:4][CH2:3][C:2](=[O:1])[N:6]1[CH2:7][C:8]1[C:13]([C:14]([F:17])([F:16])[F:15])=[CH:12][CH:11]=[CH:10][C:9]=1[O:18][CH3:19])=[O:22])[CH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1
Reactant: COc1cccc(C(F)(F)F)c1CN1C(=O)CC[C@@H]1C(=O)O
Reactant: NC(=O)C(O)C(N)Cc1ccccc1
Agent: [N-]=O
Agent: [NH-]O
Product: COc1cccc(C(F)(F)F)c1CN1C(=O)CC[C@@H]1C(=O)NC(Cc1ccccc1)C(=O)C(N)=O

Procedure:
Coupling of (R)-5-oxo-1-(2-methoxy-6-trifluoromethyl-benzyl)-pyrrolidine-2-carboxylic acid with 3-amino-2-hydroxy-4-phenylbutanamide and oxidation of the resulting hydroxyamide intermediate to the corresponding ketoamide.
Reaction SMILES: FC(F)(F)C(O)=O.[NH:8]1[CH2:12][CH2:11][CH:10]([S:13]([C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=2)(=[O:15])=[O:14])[CH2:9]1.[CH2:23]([O:30][CH2:31][CH:32]=O)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[CH2:23]([O:30][CH2:31][CH2:32][N:8]1[CH2:12][CH2:11][CH:10]([S:13]([C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=2)(=[O:15])=[O:14])[CH2:9]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: O=CCOCc1ccccc1
Reactant: O=S(=O)(c1ccc(O)cc1)C1CCNC1
Solvent: O=C(O)C(F)(F)F
Product: O=S(=O)(c1ccc(O)cc1)C1CCN(CCOCc2ccccc2)C1

Procedure:
The title compound, MS: m/e=362.2 (M+H+) was prepared from (RS)-4-(pyrrolidine-3-sulfonyl)-phenol trifluoroacetic acid salt and benzyloxyacetaldehyde.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.C(=O)(OC)O[CH2:11][CH:12]=[CH2:13]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:13][CH:12]=[CH2:11])=[CH:4][CH:3]=1
Reactant: Oc1ccc(Cl)cc1
Reactant: C=CCOC(=O)OC
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: C=CCOc1ccc(Cl)cc1
Temperature: 70 °C
Yield: 97.3 %

Procedure:
A mixture of 4-chlorophenol (1.28 g, 10 mmoles), allyl methyl carbonate (1.40 g, 12 mmoles), palladium acetate (11 mg, 0.05 mmole) and triphenyl phosphine (40 mg, 0.15 mmole) is heated at 70° C. for 2.5 hours. After removal of volatiles, the residue is subjected to bulb-to-bulb distillation (110° C., 4 mm Hg) to give 1.64 g, 97 percent of allyl 4-chlorophenyl ether.
Reaction SMILES: [C:1]([C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1)#[CH:2].Br[C:14]1[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:17]=[CH:16][N:15]=1.CCOC(C)=O.CCCCCC>C(N(CC)CC)C.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.[Cu]I>[F:21][C:20]([F:23])([F:22])[C:19]1[C:14]([C:2]#[C:1][C:3]2[CH:12]=[CH:11][C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[N:4]=2)=[N:15][CH:16]=[CH:17][CH:18]=1
Reactant: C#Cc1ccc2ccccc2n1
Reactant: FC(F)(F)c1cccnc1Br
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: FC(F)(F)c1cccnc1C#Cc1ccc2ccccc2n1
Temperature: 85 °C
Reaction time: 3 h

Procedure:
To the solution in which 2-ethynylquinoline (50 mg, 0.33 mmol) was dissolved in triethylamine (0.4 mL), PdCl2(PPh3)2 (12 mg, 0.02 mmol), CuI (6 mg, 0.03 mmol), and 2-bromo-3-trifluoromethylpyridine (110 mg, 0.5 mmol) were added, followed by stirring at 85° C. for 3 hr. The completion of the reaction was confirmed by TLC (EtOAc/Hexane=1:1). The reactant was cooled down to room temperature and filtered through Celite. The thus obtained filtrate was extracted with EtOAc (3×10 mL), to thereby obtain an organic layer. The organic layer was washed with a saturated aqueous solution of NaCl. The organic layer was then dried over anhydrous MgSO4, concentrated under reduced pressure, and purified by column chromatography (EtOAc/hexane=1:1), to thereby obtain 2-((3-(trifluoromethyl)pyridine-2-yl)ethynyl)quinoline (48 mg, 49%) as a brown solid.
Reaction SMILES: O[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([S:9][CH:10]2[CH2:13][N:12]([C:14]([C:16]3[O:17][C:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[N:19][N:20]=3)=[O:15])[CH2:11]2)=[CH:5][CH:4]=1.S(Cl)([Cl:29])=O>ClCCl>[Cl:29][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([S:9][CH:10]2[CH2:13][N:12]([C:14]([C:16]3[O:17][C:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[N:19][N:20]=3)=[O:15])[CH2:11]2)=[CH:5][CH:4]=1
Reactant: O=C(c1nnc(-c2ccccc2)o1)N1CC(Sc2ccc(CO)cc2)C1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: O=C(c1nnc(-c2ccccc2)o1)N1CC(Sc2ccc(CCl)cc2)C1
Yield: 80.2 %

Procedure:
Intermediate 60A (3.48 g, 9.47 mmol) was dissolved in dichloromethane (150 mL) and the mixture was cooled in an ice bath. While stirring, thionyl chloride (0.76 mL, 10.4 mmol) was added dropwise. The cooling bath was removed after 30 min. The mixture was stirred for 2.5 h and then evaporated to dryness. The residue was purified by column chromatography eluting with dichloromethane. There was obtained 2.93 g (80%) of 60B as a solid. 1H NMR (500 MHz, CDCl3): δ 4.22 (m, 2H), 4.57 (s, 2H), 4.65 (m, 2H), 5.14 (m, 1H), 7.29 (d, 2H), 7.36 (d, 2H), 7.53 (t, 2H), 7.59 (t, 1H), 8.16 (d, 2H), MS (APCI+) m/z 386 [M+H]+.
Reaction SMILES: [CH:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH2:13][N:14]2[C:22](=[O:23])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]2=[O:24])=[CH:5][CH:4]=1)=[CH2:2].Br[CH:26]([C:31]1[CH:36]=[C:35]([Cl:37])[C:34]([Cl:38])=[C:33]([Cl:39])[CH:32]=1)[C:27]([F:30])([F:29])[F:28].N1C=CC=CC=1C1C=CC=CN=1>ClC1C=CC=CC=1Cl.Cl[Cu]>[F:30][C:27]([F:28])([F:29])[CH:26]([C:31]1[CH:32]=[C:33]([Cl:39])[C:34]([Cl:38])=[C:35]([Cl:37])[CH:36]=1)/[CH:2]=[CH:1]/[C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH2:13][N:14]2[C:22](=[O:23])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]2=[O:24])=[CH:5][CH:4]=1
Reactant: C=Cc1ccc(CN2C(=O)c3ccccc3C2=O)c2ccccc12
Reactant: FC(F)(F)C(Br)c1cc(Cl)c(Cl)c(Cl)c1
Agent: Cl[Cu]
Agent: c1ccc(-c2ccccn2)nc1
Solvent: Clc1ccccc1Cl
Product: O=C1c2ccccc2C(=O)N1Cc1ccc(/C=C/C(c2cc(Cl)c(Cl)c(Cl)c2)C(F)(F)F)c2ccccc12
Temperature: 180 °C
Reaction time: 14 h
Yield: 54.5 %

Procedure:
To a stirred solution of 2-((4-vinylnaphthalen-1-yl)methyl)isoindoline-1,3-dione (1.5 g, 4.79 mmol) in 1,2-dichlorobenzene (15 mL) were added 1-(1-bromo-2,2,2-trifluoroethyl)-3,4,5-trichlorobenzene (3.2 g, 9.5 mmol), CuCl (24 mg, 0.24 mmol) and 2,2-bipyridyl (0.149 g, 0.95 mmol), and the resultant reaction mixture was degassed with argon for 30 min and then stirred at 180° C. for 14 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to ambient temperature and filtered, and the filtrate was concentrated under reduced pressure. Purification by flash chromatography (SiO2, 100-200 mesh; 25-30% EtOAc in petroleum ether) afforded the title compound as an off-white solid (1.5 g, 56%): mp 158-160° C.; 1H NMR (400 MHz, CDCl3) δ 8.40 (m, 1H), 7.89 (m, 2H), 7.74 (m, 2H), 7.64 (m, 2H), 7.58 (m, 2H), 7.46 (s, 2H), 7.36 (m, 2H), 6.31 (m, 1H), 5.30 (s, 2H), 4.21 (m, 1H); ESIMS m/z 572.08 ([M−H]−).
Reaction SMILES: CC(C[AlH]CC(C)C)C.C([O:12][C:13](=O)[C:14]1[CH:19]=[C:18]([CH:20]=[CH2:21])[C:17]([N:22](C(OC(C)(C)C)=O)[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[N:16][CH:15]=1)C.[NH4+].[Cl-].O>C1COCC1>[C:26]([O:25][C:23](=[O:24])[NH:22][C:17]1[C:18]([CH:20]=[CH2:21])=[CH:19][C:14]([CH2:13][OH:12])=[CH:15][N:16]=1)([CH3:29])([CH3:27])[CH3:28]
Reactant: C=Cc1cc(C(=O)OCC)cnc1N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Agent: CC(C)C[AlH]CC(C)C
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: O
Product: C=Cc1cc(CO)cnc1NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 78.3 %

Procedure:
DIBAL (25 ml, 1M in hexane) was added dropwise to a solution of 6-bis(tert-butoxycarbonyl)amino-5-vinyl-nicotinic acid ethyl ester (2.00 g, 5.1 mmol) in THF (40 ml) at 0° C. The mixture was stirred at room temperature for 1 h. NH4Cl (sat.) was added carefully followed by water, and the mixture was concentrated under reduced pressure. The residue was suspended in 5% MeOH in dichloromethane and filtered through silicagel. The filtrate was dried and concentrated under reduced pressure to give (5-hydroxymethyl-3-vinyl-pyridin-2-yl)carbamic acid tert-butyl ester (1.00 g, 78%).
Reaction SMILES: [CH2:1]([N:8]1[C:12]([C:13]([F:16])([F:15])[F:14])=[C:11]([CH3:17])[C:10](B2OC(C)(C)C(C)(C)O2)=[C:9]1[C:27]([N:29]([CH3:35])[CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[OH-].Br[C:39]1[CH:44]=[CH:43][C:42]([O:45][CH2:46][C:47]([F:50])([F:49])[F:48])=[CH:41][CH:40]=1.[OH-].[Na+]>CN(C=O)C.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH2:1]([N:8]1[C:12]([C:13]([F:16])([F:14])[F:15])=[C:11]([CH3:17])[C:10]([C:39]2[CH:40]=[CH:41][C:42]([O:45][CH2:46][C:47]([F:48])([F:49])[F:50])=[CH:43][CH:44]=2)=[C:9]1[C:27]([N:29]([CH3:35])[CH2:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: FC(F)(F)COc1ccc(Br)cc1
Reactant: Cc1c(B2OC(C)(C)C(C)(C)O2)c(C(=O)N(C)CC(C)(C)C)n(Cc2ccccc2)c1C(F)(F)F
Agent: CC(C)(C)[P]([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C
Agent: [Li+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1c(-c2ccc(OCC(F)(F)F)cc2)c(C(=O)N(C)CC(C)(C)C)n(Cc2ccccc2)c1C(F)(F)F
Temperature: 80 °C
Reaction time: 1 h
Yield: 89.7 %

Procedure:
Under an nitrogen atmosphere 1-benzyl-N,4-dimethyl-N-neopentyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)-1H-pyrrole-2-carboxamide (106 mg, 0.216 mmol) was dissolved in DMF (1 mL) and LiOH (4 mg, 0.216 mmol), bis(tri-tert-butylphosphine)palladium (0) (6 mg, 0.014 mmol) and 1-bromo-4-(2,2,2-trifluoroethoxy)benzene (50 mg, 0.196 mmol) were subsequently added. The reaction mixture was stirred at 80° C. under microwave irridation for 1 h. The mixture was cooled to RT and the reaction was stopped by addition of 1M NaOH solution (2 mL). The crude product was extracted with EtOAc (2×3 mL) and the combined organic layers were washed with water (3×1 mL), dried over Na2SO4, filtered and the solvent was removed under reduced pressure. The crude mass was purified by flash chromatography to give SC-260 (95 mg, 89.7%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:23][CH2:24][CH:25]=[CH2:26])=[C:6]([C:8]2[O:9][C:10]3[CH:16]=[CH:15][C:14]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:13][C:11]=3[N:12]=2)[CH:7]=1.[CH:27]1[C:32]([C:33]([OH:35])=[O:34])=[CH:31][C:30]2[C:36]([O:38][C:39](=O)[C:29]=2[CH:28]=1)=[O:37]>>[CH2:24]([O:23][C:5]1[CH:4]=[CH:3][C:2]([N:1]2[C:36](=[O:37])[C:30]3[C:29](=[CH:28][CH:27]=[C:32]([C:33]([OH:35])=[O:34])[CH:31]=3)[C:39]2=[O:38])=[CH:7][C:6]=1[C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:13][C:11]=2[N:12]=1)[CH:25]=[CH2:26]
Reactant: O=C(O)c1ccc2c(c1)C(=O)OC2=O
Reactant: C=CCOc1ccc(N)cc1-c1nc2cc(-c3ccccc3)ccc2o1
Product: C=CCOc1ccc(N2C(=O)c3ccc(C(=O)O)cc3C2=O)cc1-c1nc2cc(-c3ccccc3)ccc2o1

Procedure:
Prepared by the method of Example 1b), from 2-(5-amino-2-allyloxyphenyl)-5-phenylbenzoxazole (190 mg, 0.55 mmol) and 1,2,4-benzenetricarboxylic anhydride (106 mg, 0.55 mmol) the title compound was obtained (102 mg, 36%). 1H NMR (DMSO) δ 8.57(m, 1H), 8.35(dd, 1H), 8.37(s, 1H), 8.13(d, 1H), 7.94(m, 3H), 7.77(d, 1H), 7.63(m, 3H), 7.35(m, 4H), 6.04(m, 1H), 5.49(dd, 1H), 5.33(dd, 1H), 4.77(d, 2H). MS 517 m/z (M+H)+.
Reaction SMILES: C1(C[O:5][C:6]2[CH:14]=[CH:13][CH:12]=[C:11]3[C:7]=2[C:8]([C:15]2[CH2:16][CH2:17][N:18]([CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH2:19][CH:20]=2)=[CH:9][NH:10]3)CC1.C[Si](I)(C)C>>[OH:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[C:8]([C:15]1[CH2:16][CH2:17][N:18]([CH2:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:19][CH:20]=1)=[CH:9][NH:10]2
Reactant: C1=C(c2c[nH]c3cccc(OCC4CC4)c23)CCN(Cc2ccccc2)C1
Agent: C[Si](C)(C)I
Product: Oc1cccc2[nH]cc(C3=CCN(Cc4ccccc4)CC3)c12
Yield: 35.2 %

Procedure:
Following the procedure described in detail in Example 58, 1.2 gm (3.35 mMol) 4-cyclopropylmethoxy-3-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole were reacted with trimethylsilyl iodide to provide 0.359 gm (35%) of the title compound as a tan solid.