Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:25][C:26]1[C:34]([OH:35])=[CH:33][CH:32]=[C:31]2[C:27]=1[CH:28]=[CH:29][NH:30]2.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:25][C:26]1[C:34]([O:35][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:33][CH:32]=[C:31]2[C:27]=1[CH:28]=[CH:29][NH:30]2
Reactant: COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1
Reactant: Oc1ccc2[nH]ccc2c1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1cc2c(Oc3ccc4[nH]ccc4c3F)ncnc2cc1OCCCN1CCN(C)CC1
Temperature: 95 °C
Reaction time: 3 h
Yield: 42.2 %

Procedure:
A mixture of 4-chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (232 mg, 0.662 mmol), (prepared as described for the starting material in Examples 176 or 244), and 4-fluoro-5-hydroxyindole (120 mg, 0.794 mmol), (prepared as described for the starting material in Example 242), in DMF (3 ml) containing potassium carbonate (137 mg, 1 mmol) was stirred at 95° C. for 3 hours. After cooling, the residue was poured onto water (12 ml) and extracted with ethyl acetate. The organic layer was washed with water, brine, dried (MgSO4) and evaporated. The residue was purified by reversed phase C18 column chromatography eluting with methanol/ammonium carbonate (2g of ammonium carbonate/liter saturated with CO2) (60/40 followed by 70/30). The fractions containing the expected product were combined and evaporated. The residue was dissolved in ethyl acetate, dried (MgSO4) and the volatiles were removed under vacuum. The residue was triturated with ether, filtered and dried under vacuum to give 4-(4-fluoroindol-5-yloxy)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (130 mg, 42%).
Reaction SMILES: I[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])[N:10]=2)[N:7]=1.[OH:17][C:18]1[CH:19]=[CH:20][C:21]([CH3:34])=[C:22]([NH:24][C:25]([C:27]2[CH:31]([CH3:32])[CH2:30][N:29]([CH3:33])[N:28]=2)=[O:26])[CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(C)=O>O.C(OCC)(=O)C.O1CCCC1>[CH:14]1([C:12]([NH:11][C:9]2[N:10]=[C:5]3[CH:4]=[CH:3][C:2]([O:17][C:18]4[CH:19]=[CH:20][C:21]([CH3:34])=[C:22]([NH:24][C:25]([C:27]5[CH:31]([CH3:32])[CH2:30][N:29]([CH3:33])[N:28]=5)=[O:26])[CH:23]=4)=[N:7][N:6]3[CH:8]=2)=[O:13])[CH2:16][CH2:15]1
Reactant: Cc1ccc(O)cc1NC(=O)C1=NN(C)CC1C
Reactant: O=C(Nc1cn2nc(I)ccc2n1)C1CC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Solvent: O
Product: Cc1ccc(Oc2ccc3nc(NC(=O)C4CC4)cn3n2)cc1NC(=O)C1=NN(C)CC1C
Temperature: 100 °C
Reaction time: 6 h
Yield: 73.7 %

Procedure:
A mixture of N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (300 mg, 0.91 mmol), N-(5-hydroxy-2-methylphenyl)-1,4-dimethyl-4,5-dihydro-1H-pyrazole-3-carboxamide (290 mg, 1.2 mmol), cesium carbonate (600 mg, 1.8 mmol) and dimethyl sulfoxide (2 mL) was stirred at 100° C. for 6 hr. Ethyl acetate/tetrahydrofuran and water were added to the reaction mixture, and the aqueous layer was extracted with ethyl acetate/tetrahydrofuran (×4). Combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→100/0) to give the title compound (300 mg, 73%) as a white solid.
Reaction SMILES: [NH:1]1[C:5]2[C:6](=[O:12])[NH:7][CH2:8][CH2:9][C:10](=[O:11])[C:4]=2[CH:3]=[CH:2]1.[H-].[Na+].[CH3:15][Si:16]([CH2:19][CH2:20][O:21][CH2:22]Cl)([CH3:18])[CH3:17].[Cl-].[NH4+]>CN(C)C=O>[CH3:15][Si:16]([CH2:19][CH2:20][O:21][CH2:22][N:1]1[C:5]2[C:6](=[O:12])[N:7]([CH2:22][O:21][CH2:20][CH2:19][Si:16]([CH3:18])([CH3:17])[CH3:15])[CH2:8][CH2:9][C:10](=[O:11])[C:4]=2[CH:3]=[CH:2]1)([CH3:18])[CH3:17]
Reactant: C[Si](C)(C)CCOCCl
Reactant: O=C1CCNC(=O)c2[nH]ccc21
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: C[Si](C)(C)CCOCN1CCC(=O)c2ccn(COCC[Si](C)(C)C)c2C1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 48 %

Procedure:
A 500 mg amount of the 6,7-dihydropyrrolo[2,3-c]azepin-4,8(1H, 5H)dione (aldisin) described in the reference (Prager, R. et al: Aust. J. Chem., 43, p. 355-365 (1990)) was added to a 20 ml dimethylformamide suspension of 252 mg of sodium hydride (60% oil). The mixture was stirred at room temperature for 1 hour. A 1.12 ml amount of trimethylsilylethoxymethyl chloride was added under ice cooling, the mixture was stirred at room temperature for 3 hours, then a saturated aqueous solution of ammonium chloride was added and extraction was performed by ethyl acetate. The extract was washed with saturated saline, dried, filtered, and concentrated under reduced pressure to obtain a residue which was purified by silica gel column chromatography (hexane:ether acetate=6:1) to obtain 623 mg of the above-referenced compound (8) (yield 48%).
Reaction SMILES: [CH2:1](OS(C1C=CC(C)=CC=1)(=O)=O)[C:2]#[C:3][CH3:4].[C:16]1([C:18](=[CH:20][CH:21]=[CH:22][CH:23]=1)[OH:19])[OH:17].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CC(C)=O>[C:1]([O:17][C:16]1[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=1[OH:19])#[C:2][CH2:3][CH3:4]
Reactant: Oc1ccccc1O
Reactant: CC#CCOS(=O)(=O)c1ccc(C)cc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCC#COc1ccccc1O

Procedure:
A solution of 122 parts of p-toluenesulphonic acid-2-butinyl ester in 150 parts by volume of acetone is dropped into a boiling mixture of 66 parts of pyrocatechol, 75 parts of potassium carbonate, 91 parts of potassium iodide and 360 parts by volume of acetone. The suspension is refluxed for 24 hours, then cooled, filtered and evaporated. The residue is taken up in ether, repeatedly washed with water and while being cooled with ice extracted with 200 parts by volume of sodium hydroxide solution of 10 % strength. The alkaline extract is neutralised with hydrochloric acid and the product taken up with chloroform. The solvent is evaporated and the product distilled at a bath temperature of 120°C under 0.05 mm Hg pressure. The distillate crystallises; it melts at 43° to 46°C.
Reaction SMILES: C[O:2][C:3]([CH:5]1[CH2:10][C:9]([C:26]#[N:27])([C:11]2[C:19]3[C:18]4[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=4[O:16][C:15]=3[C:14]([O:24][CH3:25])=[CH:13][CH:12]=2)[CH2:8][CH2:7][C:6]1=O)=O.Cl.[NH2:30][C:31]([NH2:33])=[NH:32].C[O-].[Na+]>CO>[NH2:32][C:31]1[NH:33][C:3](=[O:2])[C:5]2[CH2:10][C:9]([C:11]3[C:19]4[C:18]5[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=5[O:16][C:15]=4[C:14]([O:24][CH3:25])=[CH:13][CH:12]=3)([C:26]#[N:27])[CH2:8][CH2:7][C:6]=2[N:30]=1
Reactant: N=C(N)N
Reactant: COC(=O)C1CC(C#N)(c2ccc(OC)c3oc4ccccc4c23)CCC1=O
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: COc1ccc(C2(C#N)CCc3nc(N)[nH]c(=O)c3C2)c2c1oc1ccccc12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of the compound obtained in example 1 (200 mg, 0.53 mmol), guanidine HCl (127 mg, 1.326 mmol) and sodium methoxide (100 mg) in 2 ml methanol was stirred overnight at room temperature. The solvent was evaporated under vacuum and the crude residue was purified by column chromatography to get 150 mg (73.3% yields) as a white solid product. MP-decomposes at 300° C.
Reaction SMILES: [CH3:1][N:2]1[C:9](=O)[CH2:8][C:6](=[O:7])[N:5]([CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[C:3]1=[O:4].O.P(Cl)(Cl)([Cl:20])=O>C(Cl)(Cl)Cl>[CH3:1][N:2]1[C:9]([Cl:20])=[CH:8][C:6](=[O:7])[N:5]([CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[C:3]1=[O:4]
Reactant: CN1C(=O)CC(=O)N(C2CCCCC2)C1=O
Reactant: O=P(Cl)(Cl)Cl
Solvent: O
Solvent: ClC(Cl)Cl
Product: Cn1c(Cl)cc(=O)n(C2CCCCC2)c1=O
Temperature: 0 °C
Reaction time: 1 h

Procedure:
35 g of 1-methyl-3-cyclohexylbarbituric acid is admixed with 15 ml of water and, then, 150 ml of phosphorus oxychloride is added. The reaction mixture is boiled for 1 hour, after which it is poured in ice-water, whereupon 35 g (dry weight) of yellow crystals are obtained. The crystals are dissolved in a small amount of chloroform and chromatographed on a column of silica gel (400 g). The first fraction is collected and concentrated to dryness. By the above procedure is obtained 14 g of 1-methyl-3-cyclohexyl-6-chlorouracil as colorless crystals, melting point: 132°-133° C.