Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C@@:4]1([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:12])[CH2:6][CH2:5]1.C(N(CC)CC)C.[CH3:31][S:32](Cl)(=[O:34])=[O:33]>C(Cl)Cl>[CH3:15][C:13]([CH3:16])([CH3:14])[C@@H:11]([N:7]1[CH2:6][CH2:5][C@:4]([CH2:3][CH2:2][NH:1][S:32]([CH3:31])(=[O:34])=[O:33])([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[O:9][C:8]1=[O:10])[CH3:12]
Reactant: C[C@H](N1CC[C@](CCN)(c2ccc(F)cc2)OC1=O)C(C)(C)C
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C[C@H](N1CC[C@](CCNS(C)(=O)=O)(c2ccc(F)cc2)OC1=O)C(C)(C)C
Temperature: 25 °C
Yield: 67.1 %

Procedure:
To a solution of (R)-6-(2-aminoethyl)-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one (144 mg, 0.45 mmol) and triethylamine (136 mg, 1.35 mmol) in CH2Cl2 (5 mL) was added methanesulfonyl chloride (153 mg, 1.35 mmol) at 0° C., and the reaction mixture was stirred at rt until the reaction was over. The reaction was quenched with H2O. The mixture was extracted with EtOAc, and the organic phase was washed with brine, dried over Na2SO4, filtered and concentrated to give crude product, which was purified by preparative TLC to afford N-(2-((S)-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)ethyl)methanesulfonamide (121 mg, 67%). LC-MS Method 1 tR=1.192, min, m/z=401.1; 1H NMR (CDCl3): 0.65 (s, 9H), 1.01-1.07 (d, 3H), 1.96-2.06 (m, 1H), 2.12-2.18 (m, 2H), 2.21-2.28 (m, 1H), 2.57-2.66 (m, 1H), 2.78 (s, 3H), 2.85-2.97 (m, 1H), 3.01-3.12 (m, 2H), 4.31-4.39 (m, 1H), 4.64-4.72 (m, 1H), 6.98-7.07 (m, 2H), 7.19-7.24 (m, 2H).
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].[CH3:5][O:6][C:7]1[CH:8]=[C:9]([C:15](=[O:23])[CH:16]=[CH:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:10]=[CH:11][C:12]=1[O:13][CH3:14].O>CN(C)C=O.[Cu]Cl>[CH3:5][O:6][C:7]1[CH:8]=[C:9]([CH:10]=[CH:11][C:12]=1[O:13][CH3:14])[C:15]([C:16]1[NH:3][N:2]=[N:1][C:17]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[O:23]
Reactant: CCOC(=O)C=CC(=O)c1ccc(OC)c(OC)c1
Reactant: [N-]=[N+]=[N-]
Agent: Cl[Cu]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)c1nn[nH]c1C(=O)c1ccc(OC)c(OC)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 64.2 %

Procedure:
Copper(I) chloride (7.5 mg, 0.075 mmol) was added at room temperature to a solution (1.0 mL) of sodium azide (74 mg, 1.1 mmol) in N,N-dimethylformamide. A solution (1.5 mL) of ethyl 4-(3,4-dimethoxyphenyl)-4-oxo-2-butenate (200 mg, 0.76 mmol) in N,N-dimethylformamide was added to this mixed solution at 5° C. The temperature of the reaction solution was raised to room temperature before the reaction solution was stirred for 8 hr. After the completion of the reaction, the reaction solution was poured into iced water, and the mixture was extracted with a saturated aqueous sodium hydrogencarbonate solution. The aqueous layer was adjusted to pH 1.8 by the addition of 2 N hydrochloric acid, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was then removed by evaporation under the reduced pressure. The oil thus obtained was dried in vacuo to give ethyl 5-(3,4-dimethoxybenzoyl)-1H-1,2,3-triazole-4-carboxylate (149 mg, 65%).
Reaction SMILES: C(N(CC)CC)C.[C:8]1(B(O)O)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[O:17]=[C:18]1[C:27]([C:28]#[N:29])=[C:26]([N:30]2[CH2:35][CH2:34][N:33]([C:36]([C:38]3[S:39][CH:40]=[CH:41][CH:42]=3)=[O:37])[CH2:32][CH2:31]2)[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[NH:19]1>ClCCl>[O:17]=[C:18]1[C:27]([C:28]#[N:29])=[C:26]([N:30]2[CH2:35][CH2:34][N:33]([C:36]([C:38]3[S:39][CH:40]=[CH:41][CH:42]=3)=[O:37])[CH2:32][CH2:31]2)[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:19]1[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: OB(O)c1ccccc1
Reactant: N#Cc1c(N2CCN(C(=O)c3cccs3)CC2)c2ccccc2[nH]c1=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: N#Cc1c(N2CCN(C(=O)c3cccs3)CC2)c2ccccc2n(-c2ccccc2)c1=O
Temperature: 25 °C
Reaction time: 48 h
Yield: 31 %

Procedure:
Cupric acetate (497 mg, 2.74 mmol), triethylamine (380 μL, 2.74 mmol), and phenyl boronic acid (335 mg, 2.74 mmol) were added successively to a solution of Compound 116 (500 mg, 1.37 mmol) in dichloromethane. The solution was stirred at room temperature for 48 h. The solution was filtered through celite and washed successively by saturated NaHCO3 solution, water, and brine. The organic phase was dried over Na2SO4 and evaporated to yield a residue which was purified by flash chromatography eluting with 0–1% MeOH in dichloromethane gradient to get 187 mg (31%) of white solids. M.P. 289° C. 1H NMR (DMSO-d6): δ 3.78 (m, 4H), 4.02 (m, 4H), 6.60 (d, J=7.6 Hz, 1H), 7.22 (m, 1H), 7.38 (m, 3H), 7.57–7.71 (m, 5H), 7.88 (dd, J=0.8, 4.8 Hz, 1H), 8.02 (d, J=7.2 Hz, 1h). EIMS m/z 441 (M+1). Anal. (C25H20N4O2S) C, H, N.
Reaction SMILES: [C:1]1([CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[Mg]Cl.[Cl:10][C:11]1[CH:23]=[CH:22][C:14]([C:15]([N:17]([CH2:20][CH3:21])[CH2:18][CH3:19])=[O:16])=[CH:13][N:12]=1.CO.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>C1COCC1>[Cl:10][C:11]1[CH:23]=[C:22]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[CH3:9])[C:14]([C:15]([N:17]([CH2:18][CH3:19])[CH2:20][CH3:21])=[O:16])=[CH:13][N:12]=1
Reactant: CCN(CC)C(=O)c1ccc(Cl)nc1
Reactant: Cc1ccccc1[Mg]Cl
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: C1CCOC1
Solvent: CO
Product: CCN(CC)C(=O)c1cnc(Cl)cc1-c1ccccc1C
Temperature: 0 °C
Reaction time: 2 h
Yield: 87.1 %

Procedure:
7.62 ml (7.62 mMol) o-Tolylmagnesium chloride solution (1M in THF) were added over 15 minutes to a solution of 0.60 g (2.54 mMol) 6-chloro- N,N-diethyl-nicotinamide in 3.0 ml THF cooled to 0° C. The reaction mixture was stirred 2 hours at room temperature, then cooled again to 0° C. and 0.41 ml methanol (10.1 mMol) were added followed by 692 mg 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (3.1 mMol). After stirring 2 hours at room temperature, the reaction mixture was concentrated under reduced pressure and 50 ml t-butyl-methylether were added at 50° C. The resulting suspension was filtered off, the filtrate was concentrated and the residue was purified by flash chromatography (eluent: ethyl acetate/n-heptane 1:1) to yield 0.67 g (86%) of 6-chloro-N,N-diethyl-4-o-tolyl-nicotinamide as a yellow oil.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].[Br:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12](Br)[CH:13]=1>>[Br:7][C:8]1[CH:13]=[C:12]([N:1]2[CH2:5][CH2:4][CH2:3][C:2]2=[O:6])[CH:11]=[N:10][CH:9]=1
Reactant: Brc1cncc(Br)c1
Reactant: O=C1CCCN1
Product: O=C1CCCN1c1cncc(Br)c1

Procedure:
In analogy to the procedure described for the preparation of intermediate A-9, pyrrolidin-2-one has been coupled to 3,5-dibromopyridine to yield the title compound as a light yellow solid. MS: 241.0, 243.0 (M+H+).
Reaction SMILES: [CH2:1]([C:3]1[C:4](N[C@@H]2C3C(=CC=CC=3)C[C@@H]2O)=[N:5][C:6]([CH2:9][CH3:10])=[CH:7][N:8]=1)[CH3:2].[CH3:22][O:23][C:24]1[CH:33]=[C:32]2[C:27]([CH2:28][CH2:29][CH2:30][CH:31]2[NH2:34])=[CH:26][CH:25]=1>>[CH2:1]([C:3]1[C:4]([NH:34][CH:31]2[C:32]3[C:27](=[CH:26][CH:25]=[C:24]([O:23][CH3:22])[CH:33]=3)[CH2:28][CH2:29][CH2:30]2)=[N:5][C:6]([CH2:9][CH3:10])=[CH:7][N:8]=1)[CH3:2]
Reactant: COc1ccc2c(c1)C(N)CCC2
Reactant: CCc1cnc(CC)c(N[C@@H]2c3ccccc3C[C@@H]2O)n1
Product: CCc1cnc(CC)c(NC2CCCc3ccc(OC)cc32)n1

Procedure:
Following the procedure for the preparation of (1R,2S)-1-[(3,6-diethylpyrazin-2-yl)amino]-2,3-dihydro-1H-inden-2-ol but substituting 7-methoxy-1,2,3,4-tetrahydronaphthalen-1-amine and making non-critical variations provided the title compound as a oil: 1H NMR (400 MHz, CDCl3) δ 7.67, 7.08, 6.92, 6.81, 5.42, 4.54, 3.75, 2.84–2.77, 2.68, 2.56, 2.10, 1.88, 1.36–1.27; (MS/CI) calcd for C19H25N3O+H 312.4, found 312.1.
Reaction SMILES: S.[Na].[N+:3]([C:6]1[CH:15]=[CH:14][C:9]2[N:10]=[C:11]([SH:13])[S:12][C:8]=2[CH:7]=1)([O-])=O>O>[NH2:3][C:6]1[CH:15]=[CH:14][C:9]2[N:10]=[C:11]([SH:13])[S:12][C:8]=2[CH:7]=1
Reactant: O=[N+]([O-])c1ccc2nc(S)sc2c1
Agent: S
Agent: [Na]
Solvent: O
Product: Nc1ccc2nc(S)sc2c1
Temperature: 20 °C
Reaction time: 4 h

Procedure:
132 Parts of sodium hydrogen sulphide was dissolved in 400 parts of water, and stirred at 20° C. 53 Parts of 6-nitro-2-mercaptobenzothiazole, prepared as described previously herein, was added over 10 minutes; the reaction mixture was then heated to 110° C., and stirred whilst boiling the mixture under reflux conditions. After four hours boiling, the mixture was cooled to between 0° and 5° C. and stirred for one hour. The product, 6-amino-2-mercaptobenzothiazole (30.3 parts), was isolated by filtration, washed sparingly with cold water and dried at 60° C. for 24 hours.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[CH2:11][CH:10]([NH:13][CH2:14][CH2:15][CH3:16])[CH2:9][CH2:8]2.[N:17]1[N:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]2=[CH:19][C:18]=1[CH2:26][C:27](O)=O>>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[CH2:11][CH:10]([N:13]([CH2:14][CH2:15][CH3:16])[CH2:27][CH2:26][C:18]1[CH:19]=[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][N:21]3[N:17]=1)[CH2:9][CH2:8]2
Reactant: O=C(O)Cc1cc2ccccn2n1
Reactant: CCCNC1CCc2cccc(OC)c2C1
Product: CCCN(CCc1cc2ccccn2n1)C1CCc2cccc(OC)c2C1

Procedure:
Synthesis works according to the preparation of A4-1 or A4-4 when using N-(8-methoxytetralin-2-yl)-N-propylamine (A2-1: R═OMe) and 2-pyrazolo[1,5-a]pyridinyl acetic acid (A3-12: R═OMe, Cy=2-pyrazolo[1,5-a]pyridinyl) (synthesis according to literature: Awano, K. Chem Pharm Bull 1992, Vol 40, p 631; Löber, S Bioorg Med Chem Lett 2002, Vol 12, p 2377) and subsequent reaction according to the synthesis of A5-1.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:15]([Cl:16])=[CH:14][N:13]=[C:12](Cl)[N:11]=2)=[CH:6][CH:5]=1.[NH2:19][C@@H:20]([CH2:23][CH3:24])[CH2:21][OH:22]>C(O)C.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:15]([Cl:16])=[CH:14][N:13]=[C:12]([NH:19][CH:20]([CH2:21][OH:22])[CH2:23][CH3:24])[N:11]=2)=[CH:6][CH:5]=1
Reactant: CC[C@H](N)CO
Reactant: COC(=O)c1ccc(-c2nc(Cl)ncc2Cl)cc1
Solvent: CCOC(C)=O
Solvent: CCO
Product: CCC(CO)Nc1ncc(Cl)c(-c2ccc(C(=O)OC)cc2)n1
Temperature: 80 °C
Reaction time: 8 h

Procedure:
4-(2,5-Dichloropyrimidin-4-yl)-benzoic acid methyl ester (70 mg, 0.25 mmol) was dissolved in ethanol with 0.22 g, 2.5 mmol, of (S)-2-aminobutan-1-ol and the reaction mixture was heated to 80° C. for 6 hours, then allowed to stand at room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed with 0.5 N HCl, brine, dried over sodium sulfate and concentrated to an oil, which was purified by chromatography on silica (EtOAc 20 to 60% in hexanes) to afford 4-[5-chloro-2-(1-hydroxymethylpropylamino)-pyrimidin-4-yl]-benzoic acid methyl ester as a colorless oil, 68 mg, 0.20 mmol, 80%. 1H NMR 500 MHz (CDCl3): 8.24 (s, 1H), 8.10 (d, 2H), 7.78 (d, 2H), 5.23 (m, 1H), 3.96 (m, 1H), 3.94 (s, 3H), 3.78 (m, 1H), 3.63 (m, 1H), 2.84 (br s, 1H), 1.56 (m, 2H), 0.96 (t, 3H).
Reaction SMILES: C(OC([N:7]1[CH2:13][C:12]2[CH:14]=[C:15]([C:18]3[CH:19]=[CH:20][C:21]4[N:25]=[C:24]([CH3:26])[N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:22]=4[CH:34]=3)[CH:16]=[CH:17][C:11]=2[O:10][CH2:9][CH2:8]1)=O)C=C.C1COCC1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)(Cl)Cl.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>[CH3:26][C:24]1[N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:31])[CH3:32])=[O:28])[C:22]2[CH:34]=[C:18]([C:15]3[CH:16]=[CH:17][C:11]4[O:10][CH2:9][CH2:8][NH:7][CH2:13][C:12]=4[CH:14]=3)[CH:19]=[CH:20][C:21]=2[N:25]=1
Reactant: C=CCOC(=O)N1CCOc2ccc(-c3ccc4nc(C)n(C(=O)OC(C)(C)C)c4c3)cc2C1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: ClC(Cl)Cl
Product: Cc1nc2ccc(-c3ccc4c(c3)CNCCO4)cc2n1C(=O)OC(C)(C)C
Yield: 106.9 %

Procedure:
7-[1-[(1,1-dimethylethoxy)carbonyl]-2-methyl-1H-benzimidazol-6-yl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylic acid 2-propenyl ester (110 mg, 0.27 mmol) was taken into THF (1 mL) followed by addition of sodium triacetoxyborohydride (254 mg, 1.2 mmol) then tetrakis(triphenylphosphine)palladium (0) (6.1 mg, 0.005 mmol) and the mixture was stirred for 1 h at room temperature. The mixture was diluted with chloroform and partitioned with dilute aqueous sodium bicarbonate. The aqueous phase was extracted twice with chloroform and the combined organic layers were dried over anhydrous sodium sulfate then filtered and concentrated to give crude 1,1-dimethylethyl 2-methyl-6-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazole-1-carboxylate (109.5 mg) as an amorphous residue. MS (EI) for C22H25N3O3: 380 (MH+).
Reaction SMILES: Br[CH2:2][CH:3]1[O:8][C:7]2[CH:9]=[C:10]([S:13]([CH3:16])(=[O:15])=[O:14])[CH:11]=[CH:12][C:6]=2[CH2:5][O:4]1.[CH2:17]([NH2:20])[CH:18]=[CH2:19]>CCO>[CH3:16][S:13]([C:10]1[CH:11]=[CH:12][C:6]2[CH2:5][O:4][CH:3]([CH2:2][NH:20][CH2:17][CH:18]=[CH2:19])[O:8][C:7]=2[CH:9]=1)(=[O:15])=[O:14]
Reactant: C=CCN
Reactant: CS(=O)(=O)c1ccc2c(c1)OC(CBr)OC2
Solvent: CCO
Product: C=CCNCC1OCc2ccc(S(C)(=O)=O)cc2O1

Procedure:
Preparation according to Example 22 using 2-(bromomethyl)-7-(methylsulfonyl)-4H-1,3-benzodioxine (30 mg, 0.10 mmol), prop-2-en-1-amine (0.50 ml, 6.7 mmol) and EtOH (1.0 ml). MS m/z (rel. intensity, 70 eV) 283 (M+, 1), 123 (6), 77 (7), 71 (5), 70 (bp).
Reaction SMILES: [H-].[Na+].[NH:3]1[CH:7]=[CH:6][N:5]=[CH:4]1.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([O:24][C@@H:25]2[O:30][C@@H:29]([CH2:31]OS(C3C=CC(C)=CC=3)(=O)=O)[CH2:28][CH2:27][CH2:26]2)[C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=2[Cl:23])=[CH:11][CH:10]=1.[I-].[Na+]>CN(C)C=O.O>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([CH:15]([O:24][C@@H:25]2[O:30][C@@H:29]([CH2:31][N:3]3[CH:7]=[CH:6][N:5]=[CH:4]3)[CH2:28][CH2:27][CH2:26]2)[C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=2[Cl:23])=[CH:13][CH:14]=1
Reactant: Cc1ccc(S(=O)(=O)OC[C@H]2CCC[C@H](OC(c3ccc(Cl)cc3)c3ccc(Cl)cc3Cl)O2)cc1
Reactant: c1c[nH]cn1
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Clc1ccc(C(O[C@H]2CCC[C@H](Cn3ccnc3)O2)c2ccc(Cl)cc2Cl)cc1
Temperature: 80 °C
Reaction time: 0.5 h
Yield: 75.3 %

Procedure:
114 mg of 55% sodium hydride were added to a solution of 323 mg of imidazole in 10 ml of dimethylformamide, and, after the mixture had been stirred at 80° C. for 30 minutes, it was cooled to room temperature. There were then added 2.20 g of trans-6-[α-(4-chlorophenyl)-2,4-dichlorobenzyloxy]-2-tosyloxymethyltetrahydropyran, dissolved in 15 ml of dimethylformamide, and then 594 mg of sodium iodide were added to the mixture. The resulting mixture stirred under a stream of nitrogen at 90°-95° C. for 4 hours, after which it was cooled, diluted with water and extracted with diethyl ether. The ethereal extract was washed with water and dried over sodium sulphate, after which it was concentrated by evaporation under reduced pressure and the residue was purified by column chromatography through silica gel eluted with a 8:1:0.1 by volume mixture of ethyl acetate, benzene and triethylamine, to give 1.346 g of the title compound as a colourless oil.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][CH:9]=[CH:10][C:3]=12.[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:20]2[CH:24]=[C:23](B3OC(C)(C)C(C)(C)O3)[C:22]([C:34]3[CH:39]=[CH:38][C:37]([N+:40]([O-:42])=[O:41])=[CH:36][CH:35]=3)=[N:21]2)=[CH:15][CH:14]=1>>[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:20]2[CH:24]=[C:23]([C:2]3[CH:7]=[CH:6][N:5]=[C:4]4[NH:8][CH:9]=[CH:10][C:3]=34)[C:22]([C:34]3[CH:39]=[CH:38][C:37]([N+:40]([O-:42])=[O:41])=[CH:36][CH:35]=3)=[N:21]2)=[CH:15][CH:14]=1
Reactant: Brc1ccnc2[nH]ccc12
Reactant: COc1ccc(Cn2cc(B3OC(C)(C)C(C)(C)O3)c(-c3ccc([N+](=O)[O-])cc3)n2)cc1
Product: COc1ccc(Cn2cc(-c3ccnc4[nH]ccc34)c(-c3ccc([N+](=O)[O-])cc3)n2)cc1

Procedure:
Following the procedure described for Intermediate 6 with 4-bromo-1H-pyrrolo[2,3-b]pyridine and 1-{[4-(methyloxy)phenyl]methyl}-3-(4-nitrophenyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole provided the title compound. ESMS [M+H]+: 426.2
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:13])[C:11]=1F)[N:8]1[CH:14]([CH3:16])[S:15][C:7]1=[C:6]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:5]2=[O:22].C(=O)([O-])[O-].[K+].[K+].[NH:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1>CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:13])[C:11]=1[N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)[N:8]1[CH:14]([CH3:16])[S:15][C:7]1=[C:6]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:5]2=[O:22]
Reactant: C1CNCCN1
Reactant: CCOC(=O)c1c2n(c3c(F)c(F)c(F)cc3c1=O)C(C)S2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1c2n(c3c(F)c(N4CCNCC4)c(F)cc3c1=O)C(C)S2
Temperature: 60 °C
Reaction time: 2 h
Yield: 73.2 %

Procedure:
Ethyl 6,7,8-trifluoro-1-methyl-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylate (0.33 g) and 0.14 g of potassium carbonate were suspended in 10 ml of N,N-dimethylformamide, 0.13 g of anhydrous piperazine was added and the mixture was stirred at 60° C. for 2 hours. N,N-Dimethylformamide was evaporated therefrom in vacuo, the residue was dissolved in chloroform, the solution was washed with water, dried over magnesium sulfate, the solvent was evaporated therefrom, the residue was subjected to a silica gel column chromatography (30 g of Wakogel C-300 being used) and eluted with chloroform-methanol (4:1) to give 0.29 g of the title product, m.p. 195°-198° C. (decompn).
Reaction SMILES: [C:1]1([N:7]2[C:13]3[CH:14]=[C:15]([Cl:18])[CH:16]=[CH:17][C:12]=3[NH:11][C:10](=[O:19])[CH2:9][C:8]2=[O:20])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[CH3:23][O:24][CH2:25][CH2:26]Br>O1CCCC1>[CH3:23][O:24][CH2:25][CH2:26][N:11]1[C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=2[N:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:8](=[O:20])[CH2:9][C:10]1=[O:19]
Reactant: O=C1CC(=O)N(c2ccccc2)c2cc(Cl)ccc2N1
Reactant: COCCBr
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COCCN1C(=O)CC(=O)N(c2ccccc2)c2cc(Cl)ccc21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
28.6 gm (0.1 mol) of 5-phenyl-7-chloro-1H-1,5-benzodiazepine-2,4-(3H,5H)-dione were suspended in 750 ml of absolute tetrahydrofuran, 5 gm of a 50% dispersion of sodium hydride in tetrahydrofuran were added to the Suspension and the mixture was stirred for two hours at room temperature, whereby everything went into solution. 21-28 gm (0.15 - 0.2 mol) of β-bromo-ethyl methyl ether were then added to the solution, and the resulting mixture was refluxed for 15-20 hours. Thereafter, the reaction solution was evaporated in vacuo, residue was admixed with water, and the aqueous mixture was extracted with methylene chloride. The methylene chloride extract was vacuum-filtered to remove insoluble components, the filtrate was evaporated, and the residue was recrystallized from isopropyl ether, yielding 22 gm (64% of theory) of the compound of the formula ##SPC7##
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].C([O-])([O-])=O.[K+].[K+].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CC(C)=O>[CH2:18]([O:11][C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:10][C:6]=1[C:7]([O:9][CH2:7][C:6]1[CH:10]=[CH:2][CH:3]=[CH:4][CH:5]=1)=[O:8])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: O=C(O)c1cc(F)ccc1O
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: O=C(OCc1ccccc1)c1cc(F)ccc1OCc1ccccc1
Temperature: 25 °C

Procedure:
To a suspension of 10.5 g (67.3 mmol) 5-fluoro-2-hydroxybenzoic acid and 37.1 g (269 mmol) fine mesh K2CO3 in 250 mL of acetone was added 18.0 μL (151.2 mmol) benzyl bromide and the resulting mixture was refluxed for 5 h. After cooling to room temperature, the solids were filtered off, the filtrate was concentrated, loaded onto a silica gel column, and eluted with EtOAc/hexanes to provide 3-1 as a white solid. Data for 3-1: 1HNMR (500 MHz, CDCl3) δ 7.55 (m, 1H), 7.4-7.3 (m, 10H), 7.1 (m, 1H), 6.95 (m, 1H), 5.35 (s, 2H), 5.1 (s, 2H) ppm.
Reaction SMILES: [C:1]1(/[C:7](/[CH3:13])=[CH:8]/[S:9]([NH2:12])(=[O:11])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:20][C:21]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:22]=1[C:23](Cl)=[O:24]>O1CCOCC1>[Cl:20][C:21]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:22]=1[C:23]([NH:12][S:9](/[CH:8]=[C:7](/[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)\[CH3:13])(=[O:10])=[O:11])=[O:24]
Reactant: O=C(Cl)c1ccc(Cl)cc1Cl
Reactant: C/C(=C\S(N)(=O)=O)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Product: C/C(=C\S(=O)(=O)NC(=O)c1ccc(Cl)cc1Cl)c1ccccc1
Temperature: 100 °C
Reaction time: 18.5 h

Procedure:
(E)-2-Phenyl-propene-1-sulfonic acid amide is dissolved in dioxane followed by the addition of potassium carbonate and 2,4-dichlorobenzoyl chloride. The resulting solution is stirred in a sealed tube at 100° C. for 18.5 h, cooled to room temperature (RT) and partitioned between 1M HCl and ethyl acetate. The aqueous phase is separated and extracted with further portions of ethyl acetate. The organic fractions are combined, washed with brine, dried over MgSO4 and concentrated in vacuo. After flash column chromatography (dichloromethane) (E)-2-phenyl-propene-1-sulfonic acid 2,4-dichlorobenzoylamide can be isolated as a colourless oil. Yield 90 mg (80%).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:4]=1[F:12])#[CH:2]>C(O)C.[Pd].[O-]S([O-])(=O)=O.[Ba+2]>[F:12][C:4]1[CH:5]=[CH:6][C:7]([N+:9]([O-:11])=[O:10])=[CH:8][C:3]=1[CH:1]=[CH2:2]
Reactant: C#Cc1cc([N+](=O)[O-])ccc1F
Agent: [Pd]
Agent: O=S(=O)([O-])[O-]
Agent: [Ba+2]
Solvent: CCO
Product: C=Cc1cc([N+](=O)[O-])ccc1F
Reaction time: 1.5 h

Procedure:
To a solution of 2-ethynyl-1-fluoro-4-nitro-benzene (70 mg, 0.42 mmol, obtained in Example 71) in 3 mL ethanol, 5% Pd/BaSO4 (48 mg) was added. The mixture was hydrogenated at 1 atm for 1.5 hrs. Catalyst was removed by filtering through a celite pad. The filtrate was concentrated to give pure 1-fluoro-4-nitro-2-vinyl-benzene.
Reaction SMILES: I[C:2]1[CH:3]=[C:4]2[N:10]=[CH:9][N:8]([CH2:11][CH2:12][N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[C:5]2=[N:6][CH:7]=1.[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:26]=[CH:27][C:28]([C:31]#[CH:32])=[N:29][CH:30]=2)=[CH:21][CH:20]=1>>[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]2[CH:26]=[CH:27][C:28]([C:31]#[C:32][C:2]3[CH:3]=[C:4]4[N:10]=[CH:9][N:8]([CH2:11][CH2:12][N:13]5[CH2:17][CH2:16][CH2:15][CH2:14]5)[C:5]4=[N:6][CH:7]=3)=[N:29][CH:30]=2)=[CH:23][CH:24]=1
Reactant: Ic1cnc2c(c1)ncn2CCN1CCCC1
Reactant: C#Cc1ccc(-c2ccc(Cl)cc2)cn1
Product: Clc1ccc(-c2ccc(C#Cc3cnc4c(c3)ncn4CCN3CCCC3)nc2)cc1

Procedure:
Prepared according to general working method I from 6-iodo-3-(2-pyrrolidin-1-yl-ethyl)-3H-imidazo[4,5-b]pyridine (300 mg, 0.88 mmol) and 5-(4-chloro-phenyl)-2-ethynyl-pyridine (187 mg, 0.88 mmol).