Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][CH:3]=1.CC([O-])(C)C.[K+].[C:17]1([CH2:23]Br)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1COCC1>[CH2:23]([N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2]([I:1])=[CH:3]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: BrCc1ccccc1
Reactant: Ic1c[nH]c2ccccc12
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: Ic1cn(Cc2ccccc2)c2ccccc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 49.8 %

Procedure:
To a solution of 3-iodoindole (1, 2.9 g, 11.93 mmol) in THF (50 mL) is added t-BuOK (1.6 g, 14.26 mmol) at 0° C. After 1 h, PhCH2Br (3.0 g, 17.54 mmol) is added dropwise over 20 min at 0° C. The reaction is then warmed to room temperature and stirred for additional 4 h, then concentrated under reduced pressure. The residue is partitioned between EtOAc (60 mL) and H2O (30 mL). The organic layer is dried (MgSO4). The solvent is then removed and purification by flash column chromatography from EtOAc-n-hexane to give 1.98 g (52%) of 2: 1H NMR (CDCl3): δ7.94–7.98 (m, 1H), 7.41–7.45 (m, 2H), 7.13–7.35 (m, 5H), 6.47–6.54 (m, 2H), 5.33 (s, 2H).
Reaction SMILES: Cl[C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.[Cl-:11].[Al+3].[Cl-].[Cl-].[CH2:15]([O:17][C:18]([C:20]1[C:24]([CH2:25][CH3:26])=[CH:23][N:22]([CH3:27])[C:21]=1[CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])=[O:19])[CH3:16]>ClCCCl>[Cl:11][C:9]1[CH:10]=[CH:2][CH:3]=[CH:4][C:5]=1[C:6]([C:23]1[N:22]([CH3:27])[C:21]([CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])=[C:20]([C:18]([O:17][CH2:15][CH3:16])=[O:19])[C:24]=1[CH2:25][CH3:26])=[O:7]
Reactant: CCOC(=O)Cc1c(C(=O)OCC)c(CC)cn1C
Reactant: [Cl-]
Reactant: O=C(Cl)c1ccc(Cl)cc1
Agent: [Al+3]
Solvent: ClCCCl
Product: CCOC(=O)Cc1c(C(=O)OCC)c(CC)c(C(=O)c2ccccc2Cl)n1C
Temperature: 25 °C
Reaction time: 10 h

Procedure:
A solution of 13.8 g. (0.0788 mole) of p-chlorobenzoyl chloride and 10.5 g. (0.0788 mole) of aluminum chloride in 120 ml. of 1,2-dichloroethane is added to a refluxing solution of 21.8 g. (0.0788 mole) of ethyl 3-ethoxycarbonyl-4-ethyl-1-methylpyrrole-2-acetate. The mixture is heated under reflux for 10 hrs. and stirred at room temperature for an additional 10 hrs. It is then poured into ice-hydrochloric acid. The organic layer is separated and the aqueous layer washed with 1,2-dichloroethane. The combined organics are washed successively with water, N,N-dimethylaminopropylamine, dilute HCl and brine. The solution is then dried over anhydrous magnesium sulfate and the solvent evaporated in vacuo. The residual red oily residue crystallizes on standing. It is recrystallized twice from methanol to give ethyl (5-o-chlorobenzoyl)-3-ethoxycarbonyl-4-ethyl-1-methylpyrrole-2-acetate as a white solid, m.p. 72°-74° C.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15]Cl)[CH2:10][CH2:9]1)=[O:7].[I-].[Na+].[CH3:19][NH2:20]>CO>[CH3:19][NH:20][CH2:15][CH2:14][N:11]1[CH2:12][CH2:13][N:8]([C:6]([C:2]2[O:1][CH:5]=[CH:4][CH:3]=2)=[O:7])[CH2:9][CH2:10]1
Reactant: O=C(c1ccco1)N1CCN(CCCl)CC1
Reactant: CN
Agent: [I-]
Agent: [Na+]
Solvent: CO
Product: CNCCN1CCN(C(=O)c2ccco2)CC1
Yield: 82 %

Procedure:
A solution of 1.0 g of 1-(2-furanylcarbonyl)-4-(2-chloroethyl)piperazine and 200 mg of sodium iodide in 40 ml of methanol which contained 25% of methylamine was reacted at 70° C. in a sealed tube for 24 hours. After allowing the reaction mixture to cool down, the reaction mixture was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (eluent: a 20:1:0.1 mixture of chloroform, methanol, and methanol containing 40% methylamine) to give 800 mg of crystals (yield: 82%).
Reaction SMILES: O=P(Cl)(Cl)[Cl:3].[NH2:6][CH:7]1[NH:12][C:11]([NH2:13])=[CH:10][C:9](=O)[NH:8]1>>[Cl:3][C:9]1[N:8]=[C:7]([NH2:6])[N:12]=[C:11]([NH2:13])[CH:10]=1
Reactant: NC1=CC(=O)NC(N)N1
Reactant: O=P(Cl)(Cl)Cl
Product: Nc1cc(Cl)nc(N)n1

Procedure:
To 500 mL of freshly distilled POCl3 at a temperature of 80-90° C. is added 100 g of 2,4-diamino-6-oxo-dihydropyrimidine (Aldrich, Milwaukee, Wis., USA). The mixture is distilled under reflux until, after approximately 2 hours, the mixture has completely dissolved. The residual POCl3 is suctioned off using vacuum and the remaining syrup is dripped slowly onto ice. The highly acidic solution is carefully neutralized by cooling it using concentrated sodium aluminate solution, and in the final stage with solid sodium carbonate. When completed the total volume of solution is approximately 1800 mL. Upon cooling a yellowish precipitate is separated out which is suctioned off and dried in a vacuum desiccator. The end product which contains mostly non-organic-salts is boiled three times, each time with 1 liter of acetone to which active charcoal is added. The extracts are cooled and the resulting clear precipitate is collected. Evaporation of the filtrates yields an additional fraction.
Reaction SMILES: [Cl:1][CH2:2][CH2:3]O.C(Cl)(Cl)Cl.Cl[S:10]([OH:13])(=[O:12])=[O:11].[OH-:14].[Na+:15]>CO>[S:10]([O-:13])([O-:14])(=[O:12])=[O:11].[Cl:1][CH2:2][CH3:3].[Na+:15].[Na+:15]
Reactant: [OH-]
Reactant: OCCCl
Reactant: O=S(=O)(O)Cl
Agent: [Na+]
Solvent: CO
Solvent: ClC(Cl)Cl
Product: CCCl
Product: O=S(=O)([O-])[O-]
Temperature: -30 °C
Reaction time: 2 h

Procedure:
A 2 liter round bottom flask was equipped with an overhead stirrer, thermometer, condenser and addition funnel with N2Inlet. 216 g of 2-chloroethanol and 550 cc of dry chloroform were charged to the flask and chilled to -30° C. Chlorosulfonic acid was added dropwise in one hour, and the reaction was allowed to warm to room temperature and stir for 11/2 hours. With the reaction solution again at -30° C., cold methanol was added dropwise followed by 300 g of 50% NaOH solution. The reaction was heated to reflux and filtered hot. The filtrate crystallized upon standing yielding white crystals, which were filtered and washed with cold methanol to yield sodium 2-chloroethane sulfate.
Reaction SMILES: [K+].[OH:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:24])/[CH:11]=[CH:12]/[C:13]2[CH:18]=[CH:17][C:16](/[CH:19]=[CH:20]/[C:21]([O-])=[O:22])=[CH:15][CH:14]=2)=[CH:6][CH:5]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[NH2:39][O:40][CH:41]1[CH2:46][CH2:45][CH2:44][CH2:43][O:42]1>C1COCC1.CN(C=O)C>[OH:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7]([C:10](=[O:24])/[CH:11]=[CH:12]/[C:13]2[CH:14]=[CH:15][C:16](/[CH:19]=[CH:20]/[C:21]([NH:39][O:40][CH:41]3[CH2:46][CH2:45][CH2:44][CH2:43][O:42]3)=[O:22])=[CH:17][CH:18]=2)=[CH:8][CH:9]=1
Reactant: NOC1CCCCO1
Reactant: O=C([O-])/C=C/c1ccc(/C=C/C(=O)c2ccc(CO)cc2)cc1
Agent: On1nnc2ccccc21
Agent: [K+]
Solvent: C1CCOC1
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: O=C(/C=C/c1ccc(/C=C/C(=O)c2ccc(CO)cc2)cc1)NOC1CCCCO1
Temperature: 25 °C
Reaction time: 8 h
Yield: 70.4 %

Procedure:
A mixture of (E)-3-{4-[(E)-3-(4-hydroxymethyl-phenyl)-3-oxo-propenyl]-phenyl}-acrylic acid potassium salt (1.39 g, 4.01 mmol), EDC (1.53 g, 8.03 mmol), HOBT (1.08 g, 8.03 mmol), TEA (1.11 ml, 8.03 mmol), NH2OTHP (939 mg, 8.03 mmol) in THF (20 ml) and DMF (20 ml) was stirred at room temperature overnight and then partitioned between water and AcOEt. The organic phase was washed with water, dried over Na2SO4 and evaporated in vacuo. The resulting solid was triturated with di-isopropylether and filtered to give 1.15 g of (E)-3-{4-[(E)-3-(4-hydroxymethyl-phenyl)-3-oxo-propenyl]-phenyl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide.
Reaction SMILES: [Cl:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[F:12][CH:13]([F:16])[CH2:14][OH:15]>>[Cl:1][C:2]1[C:3]([O:15][CH2:14][CH:13]([F:16])[F:12])=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8]
Reactant: OCC(F)F
Reactant: O=C(O)c1cnc(Cl)c(Cl)c1
Product: O=C(O)c1cnc(OCC(F)F)c(Cl)c1
Yield: 83 %

Procedure:
The title compound is prepared in 83% yield (4.12 g, white solid) from 5,6-dichloronicotinic acid (4.00 g, 20.8 mmol) and 2,2-difluoroethanol instead of 2,2,2-trifluoroethanol in a similar manner to Step-1 of Amine-1.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O.[N:12]1[CH:17]=[CH:16][CH:15]=[C:14]([NH:18][C:19]([N:21]2[CH2:24][CH:23]([O:25][C:26]3[CH:31]=[CH:30][C:29](Br)=[CH:28][N:27]=3)[CH2:22]2)=[O:20])[N:13]=1.C(=O)([O-])[O-:34].[K+].[K+]>C1COCC1.O.C(OCC)(=O)C>[N:12]1[CH:17]=[CH:16][CH:15]=[C:14]([NH2:18])[N:13]=1.[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:29]1[CH:30]=[CH:31][C:26]([O:25][CH:23]2[CH2:24][N:21]([C:19]([OH:20])=[O:34])[CH2:22]2)=[N:27][CH:28]=1
Reactant: O=C([O-])[O-]
Reactant: COc1ccccc1B(O)O
Reactant: O=C(Nc1cccnn1)N1CC(Oc2ccc(Br)cn2)C1
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COc1ccccc1-c1ccc(OC2CN(C(=O)O)C2)nc1
Product: Nc1cccnn1
Temperature: 100 °C
Yield: 68 %

Procedure:
A solution of 2-methoxyphenyl boronic acid in THF/H2O (10:1; 40 mL) was added to a microwave vial containing 3-(5-bromo-pyridin-2-yloxy)-azetidine-1-carboxylic acid pyridazin-3-ylamide (prepared as in Example 19 Step 1) 1.5 g, 4.28 mmol) and potassium carbonate (1.78 g, 12.86 mmol). Nitrogen gas was bubbled through the mixture for 5 mins then 1,1′-bis[(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with CH2Cl2 (0.350 g, 10 mole %) was added and the vial sealed and heated at 100° C. in microwave synthesiser for 30 min. The cooled reaction mixture was diluted with ethyl acetate (100 mL) and washed sequentially with sat. aqueous sodium carbonate solution (100 mL) then sat. sodium chloride solution (100 mL). Mixture dried over magnesium sulphate and filtered. Filtrate solvents were removed in vacuo to afford a brown gum, which was purified by flash chromatography, eluting with a gradient of 80 to 100% ethyl acetate in hexane to a afford a pale yellow solid. Product was triturated with diethyl ether, filtered and dried to afford the title compound as a white solid (1.098 g, 68%)