Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][C:6]=2[N:12]1[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]1.BrC1C=NC2C(C=1)=CC=CC=2N1CCN(C)CC1.[Na+].[C:38]1([S:44]([O-:46])=[O:45])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(=O)([O-])O.[Na+]>CN(C)C=O.[Cu]I.ClCCl>[CH3:18][N:15]1[CH2:16][CH2:17][N:12]([C:6]2[CH:7]=[CH:8][CH:9]=[C:10]3[C:5]=2[N:4]=[CH:3][C:2]([S:44]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)(=[O:46])=[O:45])=[CH:11]3)[CH2:13][CH2:14]1
Reactant: O=S([O-])c1ccccc1
Reactant: CN1CCN(c2cccc3cc(I)cnc23)CC1
Agent: [Cu]I
Agent: CN1CCN(c2cccc3cc(Br)cnc23)CC1
Agent: O=C([O-])O
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CN1CCN(c2cccc3cc(S(=O)(=O)c4ccccc4)cnc23)CC1
Temperature: 120 °C
Reaction time: 40 h

Procedure:
A 4:1 mixture of 3-iodo-8-(4-methyl-piperazin-1-yl)-quinoline (D2) and 3-bromo-8-(4-methyl-piperazin-1-yl)-quinoline (D1) (1.5 g), phenylsulfinic acid sodium salt, dihydrate (2.52 g, 12.6 mmol) and copper (I) iodide (2.4 g, 12.6 mmol) in N,N-dimethylformamide (25 ml) was stirred in an oil bath at 120° C. for 40 h under argon. To the reaction mixture, cooled to ambient temperature, was added 5% sodium hydrogen carbonate solution (100 ml) and dichloromethane (100 ml) with vigorous shaking. The insoluble material was filtered, washed with dichloromethane (3×20 ml) and discarded. The filtrate and washings were transferred to a separating funnel and the layers separated. The aqueous layer was extracted with dichloromethane (100 ml) and the combined organic extracts were washed with water (100 ml), dried (MgSO4) and concentrated in vacuo to an oil (0.9 g). The oil was purified by chromatography over silica gel eluting with a gradient of methanol/dichloromethane to afford an orange oil (0.28 g, Rf 0.11, methanol/dichloromethane 1:19). This material was further purified by passage through a strong cation exchange (SCX) column eluting firstly with methanol (fractions discarded) and then with methanol/aqueous ammonia-880 (10:1) to give the title compound (El) as an orange oil (0.152 g, 0.41 mmol, 7% over two steps);
Reaction SMILES: [N+](C)([O-])=O.C(=O)([O-])[O-].[K+].[K+].BrC1C=C(C(=O)/C=C(\C2C=C(Cl)C=C(Cl)C=2)/C(F)(F)F)C=CC=1C[N:35]1[C:43](=[O:44])[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:36]1=[O:45].O>C1(C)C=CC=CC=1>[C:36]1(=[O:45])[C:37]2[C:42](=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:43](=[O:44])[NH:35]1
Reactant: O=C(/C=C(\c1cc(Cl)cc(Cl)c1)C(F)(F)F)c1ccc(CN2C(=O)c3ccccc3C2=O)c(Br)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C[N+](=O)[O-]
Solvent: O
Solvent: Cc1ccccc1
Product: O=C1NC(=O)c2ccccc21
Temperature: 50 °C
Reaction time: 18 h
Yield: 344.8 %

Procedure:
A solution of anthracenylmethyl quininium bromide (200 mg), nitromethane (0.04 ml), potassium carbonate (94 mg) and 2-[[2-bromo-4-[(E)-3-(3,5-dichlorophenyl)-4,4,4-trifluoro-but-2-enoyl]phenyl]methyl]isoindoline-1,3-dione (200 mg) in toluene (2 mL) under argon, was heated for 2 hours at 50° C. then potassium carbonate (64 mg) was added. The reaction was heated for 24 hours at 50° C. then more nitromethane (0.02 mL) was added. The reaction was heated again at 50° C. for 1.5 hours then was allowed to stand at room temperature for 18 hours. Water was then added and the resulting mixture was extracted with dichloromethane and the combined organic fractions were dried over sodium sulfate. The crude product was purified by flash chromatography (0% to 25% ethyl acetate in cyclohexane) to afford 2-[[2-bromo-4-[(3R)-3-(3,5-dichlorophenyl)-4,4,4-trifluoro-3-nitromethyl)butanoyl]phenyl]methyl]isoindoline-1,3-dione (174 mg). Chiral HPLC analysis (Chiralpack IB, Heptane/isopropanol 70/30, flow: 1 mL, retention time 12.10 minutes (major enantiomer), 14.34 minutes (minor enantiomer) indicated that the reaction proceeded with 49% enantioselectivity in favor of the R enantiomer.
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([Cl:11])[N:3]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:18][C:19]1[CH:34]=[CH:33][C:22]([C:23]([C:25]2[CH:32]=[CH:31][C:28]([CH2:29]Br)=[CH:27][CH:26]=2)=[O:24])=[CH:21][CH:20]=1>CN(C=O)C.O>[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([C:23]([C:25]2[CH:32]=[CH:31][C:28]([CH2:29][N:6]3[C:5]4[C:9](=[N:10][C:2]([Cl:1])=[N:3][C:4]=4[Cl:11])[N:8]=[CH:7]3)=[CH:27][CH:26]=2)=[O:24])=[CH:33][CH:34]=1
Reactant: Clc1nc(Cl)c2[nH]cnc2n1
Reactant: O=C(c1ccc(Cl)cc1)c1ccc(CBr)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C(c1ccc(Cl)cc1)c1ccc(Cn2cnc3nc(Cl)nc(Cl)c32)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 19.1 %

Procedure:
To a solution of 2,6-dichloropurine (3.25 g) in DMF (34 ml) was added potassium carbonate (2.85 g) as well as 4-(4-chlorobenzoyl)benzyl bromide (5.32 g) and the mixture was stirred at room temperature for 24 hours. This reaction mixture was diluted with water and extracted with ethyl acetate and the extract was washed with saturated aqueous NaCl solution and dried over anhydrous sodium sulfate. The solvent was then distilled off and the residue was purified by silica gel column chromatography (hexane: ethyl acetate=1:1-1:3) to provide the title compound (1.37 g, 19%) as colorless (anhydrous) powder. 1H-NMR (CDCl3) δ5.76(2H,s), 7.21-7.85(8H,m), 8.33(1H,s).
Reaction SMILES: O=[C:2]1[CH2:11][CH2:10][CH2:9][C:8]2[CH:7]=[C:6]([O:12][S:13]([C:16]([F:19])([F:18])[F:17])(=[O:15])=[O:14])[CH:5]=[CH:4][C:3]1=2.Cl.[CH2:21]([C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([NH:37]N)[CH:32]=2)=[CH:27][CH:26]=1)[CH2:22][CH2:23][CH3:24]>>[CH2:21]([C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:32]=[C:33]3[C:34]([C:11]4[CH2:10][CH2:9][C:8]5[CH:7]=[C:6]([O:12][S:13]([C:16]([F:19])([F:18])[F:17])(=[O:15])=[O:14])[CH:5]=[CH:4][C:3]=5[C:2]=4[NH:37]3)=[CH:35][CH:36]=2)=[CH:27][CH:26]=1)[CH2:22][CH2:23][CH3:24]
Reactant: CCCCc1ccc(-c2cccc(NN)c2)cc1
Reactant: O=C1CCCc2cc(OS(=O)(=O)C(F)(F)F)ccc21
Agent: Cl
Product: CCCCc1ccc(-c2ccc3c4c([nH]c3c2)-c2ccc(OS(=O)(=O)C(F)(F)F)cc2CC4)cc1

Procedure:
The title material is prepared by reacting Trifluoro-methanesulfonic acid 5-oxo-5,6,7,8-tetrahydro-naphthalen-2-yl ester and (4′-Butyl-biphenyl-3-yl)-hydrazine hydrochloride (example 70, step 2) in an analogous manner and similar yield to example 1, step 3 except that purification is accomplished by reverse phase UV triggered HPLC. 1H NMR (400 MHz, d6-DMSO) d 11.63 (s, 1H), 7.78 (m, 2H), 7.58 (m, 4H), 7.46 (s, 1H), 7.33 (d, J=6.7 Hz, 1H), 7.28 (m, 2H), 3.09 (m, 2H), 2.95 (m, 2H), 2.64 (m, 2H), 1.60 (m, 2H), 1.35 (m, 2H), 0.94 (m, 3H); LC/MS calculated for [M+H]+ C27H25F3NO3S: 500.5, found: 500.0.
Reaction SMILES: ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl.[CH2:15]([O:17][C:18]([CH:20]1[CH2:33][C:24]2[S:25][C:26]3[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][C:27]=3[C:23]=2[CH2:22][CH2:21]1)=[O:19])[CH3:16]>O1CCOCC1>[CH2:15]([O:17][C:18]([C:20]1[CH:21]=[CH:22][C:23]2[C:27]3[CH:28]=[C:29]([CH3:32])[CH:30]=[CH:31][C:26]=3[S:25][C:24]=2[CH:33]=1)=[O:19])[CH3:16]
Reactant: CCOC(=O)C1CCc2c(sc3ccc(C)cc23)C1
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: C1COCCO1
Product: CCOC(=O)c1ccc2c(c1)sc1ccc(C)cc12
Temperature: 25 °C
Reaction time: 20 h

Procedure:
To a 500 ml. three-necked flask provided with a condenser, stirrer and dropping funnel was added 10 g. of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and 200 ml. of dioxane. To the solution, heated to reflux, was added at a rapid rate a solution of 5.5 g. of 8-methyl-1,2,3,4-tetrahydrodibenzothiophene-3-carboxylic acid ethyl ester in 50 ml. of dioxane. The solution was refluxed and stirred for 20 hours, cooled to room temperature and filtered to remove the hydroquinone. The solvent was removed in vacuo on the steam bath, and the residue was dissolved in 100 ml. of methylene chloride. The solution was passed through a column containing about 75 g. of alumina (Woelm, grade I). The solvent was removed, and the residue was crystallized from methanol. The yield of 8-methyldibenzothiophene-3-carboxylic acid ethyl ester was 4.2 g., m.p. 83°-87°.
Reaction SMILES: [CH:1]1([C:4]([OH:6])=O)[CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.[C:38]([O:42][C:43](=[O:58])[NH:44][C:45]1([C:48]2[CH:53]=[CH:52][C:51]([C:54]([NH:56][NH2:57])=[O:55])=[CH:50][N:49]=2)[CH2:47][CH2:46]1)([CH3:41])([CH3:40])[CH3:39]>CN(C=O)C.O>[C:38]([O:42][C:43](=[O:58])[NH:44][C:45]1([C:48]2[CH:53]=[CH:52][C:51]([C:54]([NH:56][NH:57][C:4]([CH:1]3[CH2:3][CH2:2]3)=[O:6])=[O:55])=[CH:50][N:49]=2)[CH2:47][CH2:46]1)([CH3:41])([CH3:39])[CH3:40]
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(C(=O)NN)cn2)CC1
Reactant: O=C(O)C1CC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)OC(=O)NC1(c2ccc(C(=O)NNC(=O)C3CC3)cn2)CC1
Temperature: 25 °C
Reaction time: 21 h
Yield: 94.1 %

Procedure:
To a solution of cyclopropyl carboxylic acid (0.20 g, 0.68 mmol) in DMF (2 mL) was added HATU (0.26 g, 0.68 mmol), Et3N (0.10 mL, 0.75 mmol) and the reaction mixture was allowed to stir at room temperature for 20 min. [1-(5-Hydrazinocarbonyl-pyridin-2-yl)-cyclopropyl]-carbamic acid tert-butyl ester (0.20 g, 0.68 mmol) in DMF (1 mL) was added and the reaction allowed to stir at room temperature for 21 h. The mixture was diluted with water and extracted with EtOAc (3×100 mL). The combined extracts were washed with satd NaHCO3, brine and dried with MgSO4. The mixture was filtered and concentrated to give {1-[5-(N′-cyclopropane-carbonyl-hydrazinocarbonyl)-pyridin-2-yl]-cyclopropyl}-carbamic acid tert-butyl ester (0.23 g, 0.64 mmol) as a light brown solid, m/z 361.7 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:31])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][CH2:13][C:14]2[S:18][C:17]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)=[N:16][C:15]=2[CH3:29])=[CH:8][C:7]=1[CH3:30].N1C=CC=CC=1.Cl[C:39]([O:41][CH3:42])=[O:40].O>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:31])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([N:12]([C:39]([O:41][CH3:42])=[O:40])[CH2:13][C:14]2[S:18][C:17]([C:19]3[CH:20]=[CH:21][C:22]([C:25]([F:27])([F:28])[F:26])=[CH:23][CH:24]=3)=[N:16][C:15]=2[CH3:29])=[CH:8][C:7]=1[CH3:30]
Reactant: COC(=O)Cl
Reactant: COC(=O)CCc1ccc(NCc2sc(-c3ccc(C(F)(F)F)cc3)nc2C)cc1C
Solvent: O
Solvent: ClCCl
Solvent: c1ccncc1
Product: COC(=O)CCc1ccc(N(Cc2sc(-c3ccc(C(F)(F)F)cc3)nc2C)C(=O)OC)cc1C
Temperature: 25 °C
Yield: 102.3 %

Procedure:
To a 0° C. solution of 3-(2-Methyl-4-{[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethyl]-amino}-phenyl)-propionic acid methyl ester (0.05 g, 0.11 mmol) and pyridine (0.027 mL, 0.33 mmol) in anhydrous CH2Cl2 (3 mL) is added methyl chloroformate (0.026 mL, 0.34 mmol) dropwise. The mixture is allowed to warm to RT overnight. Water is added, and the mixture is extracted with CH2Cl2. The combined organics are dried with MgSO4 and concentrated to yield the title compound (57 mg, quant.)
Reaction SMILES: [NH2:1][CH2:2][C:3]1([C:6]#[N:7])[CH2:5][CH2:4]1.[Br:8][C:9]1[N:10]=[C:11]([CH:29]2[CH2:31][CH2:30]2)[N:12]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:13]=1[C:14]1[CH:19]=[CH:18][N:17]=[C:16](Cl)[N:15]=1.CCN(C(C)C)C(C)C.C([O-])([O-])=O.[Na+].[Na+]>CN1C(=O)CCC1>[Br:8][C:9]1[N:10]=[C:11]([CH:29]2[CH2:31][CH2:30]2)[N:12]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:26])([CH3:27])[CH3:28])[C:13]=1[C:14]1[CH:19]=[CH:18][N:17]=[C:16]([NH:7][CH2:6][C:3]2([C:2]#[N:1])[CH2:5][CH2:4]2)[N:15]=1
Reactant: C[Si](C)(C)CCOCn1c(C2CC2)nc(Br)c1-c1ccnc(Cl)n1
Reactant: N#CC1(CN)CC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CN1CCCC1=O
Product: C[Si](C)(C)CCOCn1c(C2CC2)nc(Br)c1-c1ccnc(NCC2(C#N)CC2)n1
Temperature: 110 °C
Yield: 65.1 %

Procedure:
A mixture of 1-(aminomethyl)cyclopropanecarbonitrile (0.67 g, 7.0 mmol), 4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine (2.01 g, 4.7 mmol), DIEA (1.64 ml, 9.35 mmol), Na2CO3 (0.99 g, 9.4 mmol) and NMP (2 mL) was heated at 110° C. for 25 hours. The reaction mixture was allowed to cool to room temperature and partitioned between EtOAc (10 mL) and water (20 mL). The layers were separated and the organic portion was sequentially washed with water (20 mL), brine (10 mL), and concentrated. The resulting residue was purified by flash chromatography on silica gel eluting with an EtOAc-heptane (0-50%) gradient to provide 1-((4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)methyl)cyclopropanecarbonitrile (1.50 g, 3.06 mmol, 66%) as a white foam. LCMS(m/z) 491.1 (MH+), tR=0.99 minute.