Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:24][O:25][C:26]([CH3:41])([C:28]([O:30]CC2C=CC([N+]([O-])=O)=CC=2)=[O:29])[CH3:27])[C:8]([NH:10][C@H:11]2[C@@H:14]([C:15]([O:17][CH3:18])=[O:16])[N:13]([S:19]([O-:22])(=[O:21])=[O:20])[C:12]2=[O:23])=[O:9])[N:6]=1.[Na+:42].[H][H].C(=O)([O-])O.[Na+]>O.O1CCCC1.[Pd]>[Na+:42].[Na+:42].[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:24][O:25][C:26]([CH3:41])([C:28]([OH:30])=[O:29])[CH3:27])[C:8]([NH:10][C@H:11]2[C@@H:14]([C:15]([O:17][CH3:18])=[O:16])[N:13]([S:19]([O-:22])(=[O:21])=[O:20])[C:12]2=[O:23])=[O:9])[N:6]=1.[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:24][O:25][C:26]([C:28]([OH:30])=[O:29])([CH3:27])[CH3:41])[C:8]([NH:10][C@H:11]2[C@@H:14]([C:15]([O:17][CH3:18])=[O:16])[N:13]([S:19]([O-:22])(=[O:21])=[O:20])[C:12]2=[O:23])=[O:9])[N:6]=1
Reactant: COC(=O)[C@@H]1[C@H](NC(=O)C(=NOC(C)(C)C(=O)OCc2ccc([N+](=O)[O-])cc2)c2csc(N)n2)C(=O)N1S(=O)(=O)[O-]
Reactant: [H][H]
Agent: [Pd]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)[C@@H]1[C@H](NC(=O)C(=NOC(C)(C)C(=O)O)c2csc(N)n2)C(=O)N1S(=O)(=O)[O-]

Procedure:
In a mixture of 25 ml of water and 25 ml of tetrahydrofuran is dissolved 500 mg of sodium cis-3-{2-(2-amino-4-thiazolyl)-2-[1-methyl-1-(p-nitrobenzyloxycarbonyl)ethyloxyimino]acetamido}-4-methoxycarbonyl-2-oxoazetidine-1-sulfonate (syn-isomer), followed by addition of 500 mg of 10% palladium-on-carbon. The mixture is stirred in a hydrogen atmosphere at room temperature for one hour. After addition of 25 ml of an aqueous solution of sodium hydrogen carbonate (62 mg), the catalyst is filtered off and the filtrate is washed with ethyl acetate and concentrated under reduced pressure. The residue is chromatographed on an Amberlite XAD-II column and lyophilized to give cis-3-[2-(2-amino-4thiazolyl)-2-(1-methyl-1-carboxyethyloxyimino)acetamido]-4-methoxycarbonyl-2-oxoazetidine-1-sulfonic acid disodium salt (syn-isomer).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=[O:10].[CH3:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][C:13]=1[CH:21]=O.N1CCCCC1>C(O)C>[CH3:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][C:13]=1[CH:21]=[C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][C:2]1=[O:10]
Reactant: Cc1c(C=O)[nH]c2ccccc12
Reactant: O=C1Cc2ccccc2N1
Solvent: CCO
Solvent: C1CCNCC1
Product: Cc1c(C=C2C(=O)Nc3ccccc32)[nH]c2ccccc12
Temperature: 95 °C

Procedure:
A mixture of 2-oxindole (133 mg), 3-methyl-indole-2-carbaldehyde (190 mg) (prepared according to Synthetic Communications, 1986, 16, 1799) and piperidine (10 mg) in ethanol was heated in a sealed tube at 95° C. for 4 hours. The mixture was cooled to room temperature. The solid was collected by vacuum filtration, washed with cold ethanol and dried in vacuum oven for overnight to give 3-(3-methyl-1H-indol-2-ylmethylene)-1,3-dihydro-indol-2-one.
Reaction SMILES: [K].[CH:2]([C:5]1[CH:6]=[CH:7][C:8]2[O:12][C:11]([S:13](O)(=[O:15])=[O:14])=[C:10]([CH3:17])[C:9]=2[CH:18]=1)([CH3:4])[CH3:3].O=P(Cl)(Cl)[Cl:21]>>[CH:2]([C:5]1[CH:6]=[CH:7][C:8]2[O:12][C:11]([S:13]([Cl:21])(=[O:15])=[O:14])=[C:10]([CH3:17])[C:9]=2[CH:18]=1)([CH3:4])[CH3:3]
Reactant: Cc1c(S(=O)(=O)O)oc2ccc(C(C)C)cc12
Reactant: O=P(Cl)(Cl)Cl
Agent: [K]
Product: Cc1c(S(=O)(=O)Cl)oc2ccc(C(C)C)cc12
Temperature: 60 °C
Yield: 33 %

Procedure:
The potassium salt of 5-isopropyl-3-methylbenzofuran-2-sulfonic acid (100 mg, 0.34 mmol) was mixed with POCl3 (5 mL) and the reaction mixture was heated at 60° C. over night. The POCl3 was evaporated and the crude product was dissolved in CH2Cl2 and passed through a small amount of silica to give the title compound (30 mg, 33%).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:8])[CH2:4][C:5](=[O:7])[CH3:6].C[O-].[Na+].Br[CH2:13][C:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[O:22][C:23]([F:26])([F:25])[F:24])=[O:15]>C1COCC1>[CH3:1][O:2][C:3](=[O:8])[CH:4]([CH2:13][C:14](=[O:15])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[O:22][C:23]([F:24])([F:25])[F:26])[C:5](=[O:7])[CH3:6]
Reactant: O=C(CBr)c1ccccc1OC(F)(F)F
Reactant: COC(=O)CC(C)=O
Agent: C[O-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(=O)C(CC(=O)c1ccccc1OC(F)(F)F)C(C)=O
Temperature: 25 °C
Reaction time: 17 h
Yield: 71.6 %

Procedure:
To a solution of 2.6 g of 3-oxo-butyric acid methyl ester in THF (50 ml) and 4.6 ml of a solution of sodium methoxide (5.4 M in methanol) was added over 15 minutes a solution of 6.7 g of 2-bromo-1-[2-(trifluoromethoxy)phenyl]-ethanone in 30 ml of THF. The reaction mixture was allowed to stir at room temperature for 17 hours. The solvent was removed, the residue was diluted in diethyl ether and washed several times with water. The organic phase was dried with sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography (silica gel; heptane/ethyl acetate) to give 5.1 g of the title compound. MS (EI) 319.1 (M+H)+.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[C:12](=[O:13])[C:11]2[C:6](=[CH:7][C:8]([Cl:14])=[CH:9][CH:10]=2)[N:5]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:4]=1[C:21]1[O:22][CH:23]=[CH:24][N:25]=1.[O:26]1[C:30]2[CH:31]=[CH:32][C:33]([C:35](Cl)=[O:36])=[CH:34][C:29]=2[O:28][CH2:27]1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[Cl:14][C:8]1[CH:7]=[C:6]2[C:11]([C:12](=[O:13])[C:3]([CH2:2][NH:1][C:35]([C:33]3[CH:32]=[CH:31][C:30]4[O:26][CH2:27][O:28][C:29]=4[CH:34]=3)=[O:36])=[C:4]([C:21]3[O:22][CH:23]=[CH:24][N:25]=3)[N:5]2[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:10][CH:9]=1
Reactant: O=C(Cl)c1ccc2c(c1)OCO2
Reactant: NCc1c(-c2ncco2)n(-c2ccccc2)c2cc(Cl)ccc2c1=O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C(NCc1c(-c2ncco2)n(-c2ccccc2)c2cc(Cl)ccc2c1=O)c1ccc2c(c1)OCO2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In a 20 mL vial, 3-(aminomethyl)-7-chloro-2-(oxazol-2-yl)-1-phenylquinolin-4(1H)-one (intermediate A) (20 mg, 0.057 mmol), benzo[d][1,3]dioxole-5-carbonyl chloride (12 mg, 0.065 mmol) and N,N-(dimethylamino)pyridine (DMAP) (1.0 mg, 0.085 mmol) were combined with methylene chloride (1.5 mL) to give a brown solution. N,N-diisopropylethylamine (37 mg, 0.050 mL, 0.28 mmol) was added. The reaction mixture was stirred overnight at room temperature. In the morning, LC/MS indicated complete conversion to the desired product. The reaction mixture was diluted with 10 mL methylene chloride, then the organic solution was washed with water. The organic phase was dried over Na2SO4, filtered, then concentrated over silica gel. The silica gel-supported crude product was loaded onto a 25 gram SiliCycle column. Flash chromatography (50% ethyl acetate-hexanes ramped to 75% ethyl acetate-hexanes) afforded benzo[1,3]dioxole-5-carboxylic acid (7-chloro-2-oxazol-2-yl-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-amide as a brown oil. 1H NMR (300 MHz, chloroform-d) δ ppm 8.36 (d, J=8.67 Hz, 1H) 7.50 (d, J=0.94 Hz, 1H) 7.34-7.42 (m, 4H) 7.30 (dd, J=8.67, 1.88 Hz, 1H) 7.15-7.26 (m, 6H) 7.05 (d, J=0.94 Hz, 1H) 6.77 (d, J=1.88 Hz, 1H) 6.70 (d, J=8.10 Hz, 1H) 5.91 (s, 2H) 4.37 (s, 2H). MS calcd. for C27H18ClN3O5 [(M+H)+] 499.9, obsd. 500.0.
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([NH:11][C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[O:13])[CH:7]=[C:8]([F:10])[CH:9]=1.I[CH3:21].O>CN(C)C=O>[F:10][C:8]1[CH:7]=[C:6]([N:11]([CH3:21])[C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[O:13])[CH:5]=[C:4]([F:3])[CH:9]=1
Reactant: CI
Reactant: O=C(Nc1cc(F)cc(F)c1)c1ccccn1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CN(C(=O)c1ccccn1)c1cc(F)cc(F)c1
Temperature: 65 °C
Yield: 56 %

Procedure:
To a suspension of 80% sodium hydride (1.22 g, 41 mmol) in anhydrous dimethylformamide (90 mL), was added dropwise a solution of N-(3,5-difluorophenyl)-2-pyridinecarboxamide, prepared by the process of Example 1, Step 1 (8.71 g, 37 mmol) in dimethylformamide (30 mL). The reaction mixture was warmed to 65° C. for 1 hour and then treated with iodomethane (2.60 mL, 42 mmol) at room temperature. After 2.5 hours the reaction mixture was poured into water (500 mL) and extracted with ethyl acetate (2×300 mL). The combined organic layers were washed with 75% brine, dried, preabsorbed onto silica gel, and flash chromatographed (300 g, elution with 40% ethyl acetate in petroleum ether) to yield pure N-(3,5-difluorophenyl)-N-methyl-2-pyridinecarboxamide (5.16 g, 21 mmol, 56%, m.p. 102°-104° C.), which was reacted with Lawesson's reagent (4.36 g, 11 mmol) in anhydrous toluene (65 mL) at reflux temperature for 1.5 hours. The toluene was evaporated and the residue was dissolved in dichloromethane, preadsorbed onto silica gel, flash chromatographed (300 g, elution with 10% ethyl acetate in petroleum ether), and recrystallized from ethyl acetate in petroleum ether to afford a yellow solid (2.36 g, 24%), m.p. 131°-134° C.
Reaction SMILES: [N:1]1([C:6]2[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=2)[C:9](O)=[O:10])[CH:5]=[CH:4][CH:3]=[N:2]1.S(Cl)(Cl)=O.C[N:20](C=O)C.C([O-])(=O)C.[NH4+]>C1C=CC=CC=1>[N:1]1([C:6]2[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=2)[C:9]([NH2:20])=[O:10])[CH:5]=[CH:4][CH:3]=[N:2]1
Reactant: O=C(O)c1cccc(-n2cccn2)c1
Reactant: CN(C)C=O
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: c1ccccc1
Solvent: O=S(Cl)Cl
Product: NC(=O)c1cccc(-n2cccn2)c1
Yield: 80 %

Procedure:
To a suspension of 3-(1H-pyrazol-1-yl)-benzoic acid [see WO 00/21951] (104 g, 0.55 mol) in anhydrous benzene (500 ml) was added thionyl chloride (85 g, 0.715 mol) and DMF (0.5 ml). The mixture was heated at reflux for 3 hours, then evaporated under reduced pressure. The residue was dissolved in anhydrous THF (100 ml) and evaporated. The residue was dissolved in anhydrous acetone (600 ml), and treated with ammonium acetate (77 g, 1 mol). The mixture was heated at reflux for 12 hours, solvent was evaporated and the residue treated with cold water (2000 ml). The resulting precipitate was filtered, washed with cold water (200 ml) and recrystallised from absolute ethanol (600 ml) to give 3-(1H-pyrazol-1-yl)benzamide (82 g, 80%). A solution of this material (82 g, 0.44 mol) in THF was added dropwise to a solution of LiAlH4 (25 g, 0.66 mol) in anhydrous THF (800 ml). The mixture was heated at reflux for 4 hours, cooled and quenched by the sequential addition of water (25 ml), 15% aqueous NaOH (25 ml), and water (50 ml). The inorganic by-products were filtered off and washed several times with diethyl ether (overall volume 1000 ml). The combined filtrates were dried over Na2SO4, filtered and evaporated. The residue was dissolved in methanol (400 ml), the solution was treated with activated carbon (10 g), and the mixture was refluxed for 40 minutes, then filtered and evaporated. The residue was treated with 1N HCl in ether (1000 ml), and the precipitate formed was filtered, washed with ether and dried to give the title compound (53 g, 70%).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]2[C:16]([C:17]#[N:18])=[C:15]([N:19]=[CH:20][N:21](C)C)[NH:14][N:13]=2)=[CH:7][CH:6]=1)(=[O:3])[CH3:2].Cl.[Cl:25][C:26]1[CH:27]=[C:28]([CH:30]=[CH:31][CH:32]=1)N>CO>[C:1]([NH:4][C:5]1[CH:6]=[CH:7][C:8]([NH:11][C:12]2[C:16]3[C:15](=[N:19][CH:20]=[N:21][C:17]=3[NH:18][C:31]3[CH:30]=[CH:28][CH:27]=[C:26]([Cl:25])[CH:32]=3)[NH:14][N:13]=2)=[CH:9][CH:10]=1)(=[O:3])[CH3:2]
Reactant: Nc1cccc(Cl)c1
Reactant: CC(=O)Nc1ccc(Nc2n[nH]c(N=CN(C)C)c2C#N)cc1
Agent: Cl
Solvent: CO
Product: CC(=O)Nc1ccc(Nc2n[nH]c3ncnc(Nc4cccc(Cl)c4)c23)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A suspension of 6.32 g (20.3 mmol) of 3-(4-acetylamino-phenylamino)-4-cyano-5-(dimethylamino-methyleneamino)-pyrazole and 4 g (24.4 mmol) of 3-chloro-aniline hydrochloride in 50 ml of methanol is heated under reflux for 96 hours and then cooled to room temperature. The reaction mixture is filtered and the filter residue is digested for 1/2 hour in 50 ml of 1N sodium hydroxide solution. Filtering and washing with water yield the title compound; m.p. 290-291° C. (decomp.).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][S:9]([C:12]2[CH:17]=[CH:16][C:15](F)=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[CH:4][C:3]=1[N+:19]([O-:21])=[O:20].[CH:22]1([CH2:25][NH2:26])[CH2:24][CH2:23]1.O>CN1CCCC1=O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([NH:26][CH2:25][CH:22]3[CH2:24][CH2:23]3)=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[CH:4][C:3]=1[N+:19]([O-:21])=[O:20]
Reactant: Nc1ccc(OS(=O)(=O)c2ccc(F)cc2)cc1[N+](=O)[O-]
Reactant: NCC1CC1
Solvent: O
Solvent: CN1CCCC1=O
Product: Nc1ccc(OS(=O)(=O)c2ccc(NCC3CC3)cc2)cc1[N+](=O)[O-]

Procedure:
A solution of 4-fluoro-benzenesulfonic acid 4-amino-3-nitro-phenyl ester (800 mg) and cyclopropylmethylamine (890 μl) in N-methylpyrrolidinone (8 ml) was heated at 110° C. in a sealed tube for 14 hours. The reaction mixture was then poured into water (150 ml) and extracted three times with ethyl acetate (40 ml). The combined extracts were dried over magnesium sulfate and then evaporated. The residue was subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and heptane (50:50, v/v) to give 4-(cyclopropylmethyl-amino)-benzenesulfonic acid 4-amino-3-nitro-phenyl ester (786 mg) as a yellow solid.
Reaction SMILES: C(NC(C)C)(C)C.[Li]CCCC.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1.C1C[O:23][CH2:22][CH2:21]1>>[F:13][C:14]1[C:19]([C:22](=[O:23])[CH3:21])=[CH:18][CH:17]=[CH:16][N:15]=1
Reactant: Fc1ccccn1
Reactant: C1CCOC1
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Product: CC(=O)c1cccnc1F
Temperature: -78 °C
Reaction time: 0.33 h

Procedure:
A solution of 3.13 mL (30.90 mmol) of freshly distilled diisopropylamine in 10 mL of anhydrous THF under nitrogen cooled to −78° C. was treated dropwise with 19.31 mL (30.90 mmol) of a 1.6 M solution of n-BuLi in hexanes. The resulting solution was stirred at −78° C. for approximately 20 minutes, and was briefly (5-10 minutes) warmed to −40° C., then recooled to −78° C. At 30 minutes post addition, 3.00 g (30.90 mmol) of 2-fluoropyridine was added dropwise to the reaction. The resulting solution was stirred at −78° C. for 30 minutes. The reaction was treated dropwise with a solution of 3.16 mL (30.90 mmol) of the Weinreb amide in 30 mL of THF. The resulting solution was stirred 18 hours, allowing the bath to slowly evaporate and the reaction temperature to rise to room temperature. The reaction was treated with 5 mL of 1N HCl, and was concentrated to remove most of the THF. The residue was extracted twice with EtOAc, and the combined extracts were washed with 1N HCl, saturated aqueous NaHCO3 solution, and brine, and were dried over anhydrous MgSO4. Filtration and concentration of the filtrate provided a crude orange oil, which was purified by flash chromatography over silica gel with 3:1 Hexanes/EtOAc to provide 1.10 g of the title product as an orange oil. 1H NMR (CDCl3): 2.72 (s, 3H), 7.33 (m, 1H), 8.34 (m, 1H), 8.41 (m, 1H).
Reaction SMILES: [C:1]([O:5][CH2:6][CH3:7])(=[O:4])[C:2]#[CH:3].[F:8][C:9]1[CH:14]=[CH:13][C:12]([SH:15])=[CH:11][CH:10]=1>>[F:8][C:9]1[CH:14]=[CH:13][C:12]([S:15][CH:3]=[CH:2][C:1]([O:5][CH2:6][CH3:7])=[O:4])=[CH:11][CH:10]=1
Reactant: C#CC(=O)OCC
Reactant: Fc1ccc(S)cc1
Product: CCOC(=O)C=CSc1ccc(F)cc1

Procedure:
Using Example 15 procedures, ethyl propiolate and 4-fluorobenzenethiol are reacted, yielding ethyl 3-(4-fluorophenylthio)-2-propenoate. Three equiv. of this is then combined with 1 equiv. of phenyl(trifluoromethyl)mercury and 3 equiv. of dry powdered sodium iodide. This mixture is refluxed in benzene for 15-20 hr, then filtered and solvent is removed to give ethyl 3-(4-fluorophenylthio)-2,2-difluorocyclopropanecarboxylate.
Reaction SMILES: C([O:8][C:9](=[O:41])[CH2:10][C:11]1([C:16]([NH:18][CH2:19][CH:20]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=3)=[CH:31][CH:30]=2)[C:21]([O:23]C(C)(C)C)=[O:22])=[O:17])[CH2:15][CH2:14][CH2:13][CH2:12]1)C1C=CC=CC=1>CCOC(C)=O.[Pd]>[C:9]([CH2:10][C:11]1([C:16]([NH:18][CH2:19][CH:20]([CH2:28][C:29]2[CH:30]=[CH:31][C:32]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=3)=[CH:33][CH:34]=2)[C:21]([OH:23])=[O:22])=[O:17])[CH2:15][CH2:14][CH2:13][CH2:12]1)([OH:41])=[O:8]
Reactant: CC(C)(C)OC(=O)C(CNC(=O)C1(CC(=O)OCc2ccccc2)CCCC1)Cc1ccc(-c2ccccn2)cc1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: O=C(O)CC1(C(=O)NCC(Cc2ccc(-c3ccccn3)cc2)C(=O)O)CCCC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Tert-Butyl 3-(1-(2-(benzyloxy)-2-oxoethyl)cyclopentanecarboxamido)-2-(4-(pyridin-2-yl)benzyl)propanoate was dissolved in EtOAc (5 ml) and hydrogenated with 10% Pd/C under H2 at room temperature. After 3 hours, the reaction mixture was filtered and concentrated under reduced pressure. To the obtained residue in DCM (1.00 ml) at room temperature was added TFA, and the reaction mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure. The obtained residue was purified by reverse phase HPLC [5 to 35% ACN-water (0.1°/oTFA) over 10 min by X-bridge phenyl column] to give the title compound (48 mg). LCMS (condition A): 411.3 (M+1); retention time=1.24 min. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.44-1.62 (m, 6H), 1.96-2.06 (m, 2H), 2.59 (dd, J=18.7, 16.4 Hz, 2H), 2.74-2.91 (m, 3H), 3.14-3.24 (m, 1H), 3.24-3.33 (m, 1H), 7.34 (d, J=8.3 Hz, 2H), 7.47-7.53 (m, 1H), 7.68 (t, J=5.6 Hz, 1H), 7.96 (d, J=8.3 Hz, 2H), 8.03-8.11 (m, 2H), 8.68-8.74 (m, 1H).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[NH2:7][C:8]1[C:21]([Cl:22])=[CH:20][C:19]([Cl:23])=[CH:18][C:9]=1[C:10]([N:12]=[S:13]([CH2:16][CH3:17])[CH2:14][CH3:15])=[O:11].[Cl:24][C:25]1[C:26]([N:31]2[C:35]([C:36](Cl)=[O:37])=[CH:34][C:33]([C:39]([F:42])([F:41])[F:40])=[N:32]2)=[N:27][CH:28]=[CH:29][CH:30]=1>C(#N)C>[Cl:24][C:25]1[C:26]([N:31]2[C:35]([C:36]([NH:7][C:8]3[C:9]([C:10](=[O:11])[N:12]=[S:13]([CH2:14][CH3:15])[CH2:16][CH3:17])=[CH:18][C:19]([Cl:23])=[CH:20][C:21]=3[Cl:22])=[O:37])=[CH:34][C:33]([C:39]([F:42])([F:40])[F:41])=[N:32]2)=[N:27][CH:28]=[CH:29][CH:30]=1
Reactant: O=C(Cl)c1cc(C(F)(F)F)nn1-c1ncccc1Cl
Reactant: CCS(CC)=NC(=O)c1cc(Cl)cc(Cl)c1N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCS(CC)=NC(=O)c1cc(Cl)cc(Cl)c1NC(=O)c1cc(C(F)(F)F)nn1-c1ncccc1Cl
Reaction time: 6 h
Yield: 88.4 %

Procedure:
To a suspension of potassium carbonate (8.08 g, 58.5 mmol, 1.50 equiv.) and 2-amino-3,5-dichloro-N-(diethyl-λ4-sulfanylidene)benzamide (11.43 g, 38.98 mmol) in acetonitrile (100 mL) was added a solution of 2-(3-chloro-2-pyridyl)-5-(trifluoromethyl)pyrazole-3-carbonyl chloride (15.8 g, 43.31 mmol, 1.10 equiv.) in acetonitrile (50 mL) at room temperature. After 6 h at this temperature, the solids were filtered off. The resulting filtrate was washed with water and dried over Na2SO4. After filtration, the filtrate was concentrated in vacuum and the resulting solids were crystallized from diisopropyl ether to yield the title compound (19.53 g, 88%).
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH:8]([N:12]([CH2:16][CH:17]3[CH2:22][CH2:21][N:20]([S:23]([CH3:26])(=[O:25])=[O:24])[CH2:19][CH2:18]3)[CH2:13][CH2:14][CH3:15])[CH2:9]2)=[CH:4][CH:3]=1.[NH2:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[OH-].[Na+]>[NH2:27][C:28]1[CH:33]=[C:32]([C:4]2[CH:5]=[C:6]3[C:11]([CH2:10][CH2:9][CH:8]([N:12]([CH2:16][CH:17]4[CH2:22][CH2:21][N:20]([S:23]([CH3:26])(=[O:25])=[O:24])[CH2:19][CH2:18]4)[CH2:13][CH2:14][CH3:15])[CH2:7]3)=[CH:2][CH:3]=2)[CH:31]=[CH:30][CH:29]=1
Reactant: Nc1cccc(B(O)O)c1
Reactant: CCCN(CC1CCN(S(C)(=O)=O)CC1)C1CCc2ccc(Br)cc2C1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Na+]
Agent: [OH-]
Product: CCCN(CC1CCN(S(C)(=O)=O)CC1)C1CCc2ccc(-c3cccc(N)c3)cc2C1
Temperature: 80 °C
Reaction time: 4 h

Procedure:
A 1 mL solution of (7-bromo-1,2,3,4-tetrahydro-naphthalen-2-yl)-(1-methanesulfonyl-piperidin-4-ylmethyl)-propyl-amine (25 mmole in DMA) was added to a tube containing 2-3 mg Pd(PPh3)4 catalyst followed by 120 μL of a solution of 3-amino phenyl boronic acid (30 mmole in DMA), and 200 μL 1N aq. NaOH. The solution was shaken at 80° C. for 4 h, concentrated, and purified by chromatography to yield [7-(3-amino-phenyl)-1,2,3,4-tetrahydro-naphthalen-2-yl]-(1-methanesulfonyl-piperidin-4-ylmethyl)-propyl-amine 112[M+H]+=456.
Reaction SMILES: [Br:1]C1C2C(=CC(C3SC4C(C5C=CC(Cl)=CC=5)=C([C@H](OC(C)(C)C)C(OCC)=O)C(C)=CC=4N=3)=CC=2)N(C)N=1.N[C:41]1[C:49]2[C:44](=[CH:45][CH:46]=[C:47]([C:50]3[S:51][C:52]4[C:58]([C:59]5[CH:64]=[CH:63][C:62]([Cl:65])=[CH:61][CH:60]=5)=[C:57]([C@H:66]([O:72][C:73]([CH3:76])([CH3:75])[CH3:74])[C:67]([O:69][CH2:70][CH3:71])=[O:68])[C:56]([CH3:77])=[CH:55][C:53]=4[N:54]=3)[CH:48]=2)[N:43]([CH3:78])[N:42]=1>>[Br:1][C:41]1[C:49]2[C:44](=[CH:45][CH:46]=[C:47]([C:50]3[S:51][C:52]4[C:58]([C:59]5[CH:64]=[CH:63][C:62]([Cl:65])=[CH:61][CH:60]=5)=[C:57]([C@H:66]([O:72][C:73]([CH3:76])([CH3:75])[CH3:74])[C:67]([O:69][CH2:70][CH3:71])=[O:68])[C:56]([CH3:77])=[CH:55][C:53]=4[N:54]=3)[CH:48]=2)[N:43]([CH3:78])[N:42]=1
Reactant: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(-c3ccc4c(Br)nn(C)c4c3)sc2c1-c1ccc(Cl)cc1
Reactant: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(-c3ccc4c(c3)c(N)nn4C)sc2c1-c1ccc(Cl)cc1
Product: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(-c3ccc4c(c3)c(Br)nn4C)sc2c1-c1ccc(Cl)cc1

Procedure:
prepared in a manner similar to (S)-ethyl 2-(2-(3-bromo-1-methyl-1H-indazol-6-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate except using (S)-ethyl 2-(2-(3-amino-1-methyl-1H-indazol-5-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate instead of (S)-ethyl 2-(2-(3-amino-1-methyl-1H-indazol-6-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate. LCMS-ESI+: calc'd for C30H29BrClN3O3S: 626.1, 628.1, 630.1 (M+H+); Found; 626.1, 628.1, 630.1 (M+H+).
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][C@H:15]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][C:22]3[O:27][CH2:26][CH2:25][N:24]([CH2:28][CH2:29][CH2:30][O:31][CH3:32])[C:23]=3[CH:33]=2)[C@@H:14]([C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)[CH2:13][C@H:12]1[C:42](O)=[O:43])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:45]1([C:51]2[CH:52]=[C:53]([CH:56]=[CH:57][CH:58]=2)[CH2:54][NH2:55])[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][C@H:15]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][C:22]3[O:27][CH2:26][CH2:25][N:24]([CH2:28][CH2:29][CH2:30][O:31][CH3:32])[C:23]=3[CH:33]=2)[C@@H:14]([C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)[CH2:13][C@H:12]1[C:42](=[O:43])[NH:55][CH2:54][C:53]1[CH:52]=[C:51]([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH:58]=[CH:57][CH:56]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NCc1cccc(-c2ccccc2)c1
Reactant: COCCCN1CCOc2ccc(CO[C@H]3CN(C(=O)OCc4ccccc4)[C@H](C(=O)O)C[C@@H]3c3ccc(OC)cc3)cc21
Product: COCCCN1CCOc2ccc(CO[C@H]3CN(C(=O)OCc4ccccc4)[C@H](C(=O)NCc4cccc(-c5ccccc5)c4)C[C@@H]3c3ccc(OC)cc3)cc21

Procedure:
According to general procedure D, 0.07 g of (2S,4R,5R)-4-(4-methoxy-phenyl)-5-[4-(3-methoxy-propyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-piperidine-1,2-dicarboxylic acid 1-benzyl ester and 3-phenylbenzylamine are reacted to afford the title compound as a colourless solid. Rf=0.15 (EtOAc-heptan 1:1:1); Rt=5.62.