Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1(/[C:7](=[N:9]/[NH:10][C:11](=[O:18])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)/[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CS(O)(=O)=O.O.COC(OC)(C)C.[H][H]>CC(C)=O>[C:1]1([CH:7]([NH:9][NH:10][C:11](=[O:18])[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH3:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: [H][H]
Reactant: C/C(=N\NC(=O)c1ccccc1)c1ccccc1
Agent: CS(=O)(=O)O
Solvent: O
Solvent: CC(C)=O
Solvent: COC(C)(C)OC
Product: CC(NNC(=O)c1ccccc1)c1ccccc1

Procedure:
In a 120 mL high-pressure autoclave were charged (E)-N′-(1-phenylethylidene)benzohydrazide (119 mg) [mw. 238.28, 0.5 mmol], [Rh(cod) (S,S)-ptbp-skewphos)]OTf (5.1 mg) [mw. 1025.08, 5.0 μmol, s/c 100], and methanesulfonic acid (0.5 mg) [mw. 96.11, 5.0 μmol, 0.01 eq.]. The system was argon-substituted 7 times. 10 mL Schlenk flask was substituted with argon, and pure water (9 mg) [mw. 18.02, 0.5 mmol, 1.0 eq.], 2,2-dimethoxypropane (0.18 mL) [mw. 104.15, d=0.85, 1.5 mmol, 3.0 eq.] and dehydrated acetone for organic synthesis (5 mL) were added. The solution was fed into an autoclave by argon pressure supply. The system was substituted with hydrogen gas, and the mixture was stirred with hydrogen gas pressurization at 1.0 MPa for 2 hr. The system was depressurized, and analyzed by high performance liquid chromatography to find that the starting material, (E)-N′-(1-phenylethylidene)benzohydrazide, remained by 38%, and the resultant product, N′-(1-phenylethyl)benzohydrazide was produced by 59%, and the decomposed product, acetophenone, was produced by 1%.
Reaction SMILES: [Na].[C:2]([CH:5]([C:11]([CH3:20])([CH3:19])[CH:12](Cl)[CH2:13][C:14]([Cl:17])([Cl:16])[Cl:15])[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:4])[CH3:3].Cl>C(O)C>[C:2]([C:5]1([C:6]([O:8][CH2:9][CH3:10])=[O:7])[C:11]([CH3:20])([CH3:19])[CH:12]1[CH2:13][C:14]([Cl:17])([Cl:16])[Cl:15])(=[O:4])[CH3:3]
Reactant: CCOC(=O)C(C(C)=O)C(C)(C)C(Cl)CC(Cl)(Cl)Cl
Agent: Cl
Agent: [Na]
Solvent: CCO
Product: CCOC(=O)C1(C(C)=O)C(CC(Cl)(Cl)Cl)C1(C)C
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 53.6 %

Procedure:
Sodium (0.15 g) was dissolved in 10 ml of absolute ethanol, and 2.29 g of ethyl 2-acetyl-4,6,6,6-tetrachloro-3,3-dimethylhexanoate was added, while the reaction mixture was cooled with ice. After stirring at room temperature for 15 minutes, the mixture was rendered neutral with an ethereal solution of hydrogen chloride, while cooled with ice, and then the solvent was distilled off. The resulting residue was dissolved in diethyl ether, and the solution was washed with water, dried over anhydrous magnesium sulfate, and distilled to give an oily substance having a boiling point of 108°-112° C./0.6 mmHg. Purification by column chromatography (silica gel-benzene) gave 1.1 g (50% yield) of ethyl 1-acetyl-2-(2,2,2-trichloroethyl)-3,3-dimethylcyclopropanecarboxylate.
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.NC(N)=[O:11].C(=O)(O)[O-].[Na+].OO>O.S([O-])([O-])(=O)=O.[Mn+2]>[CH2:1]1[O:11][CH:2]1[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C=Cc1ccccc1
Reactant: NC(N)=O
Agent: [Mn+2]
Agent: O=C([O-])O
Agent: O=S(=O)([O-])[O-]
Solvent: O
Product: c1ccc(C2CO2)cc1
Reaction time: 10 h

Procedure:
To a mechanically stirred solution of styrene (1.0 mol), urea (40.8 mol), sodium bicarbonate (0.6 mol) and manganese sulphate (0.001 mol) in 500 ml of water at 0° C. is added 50% aqueous hydrogen peroxide (2.2 mol) drop-wise over a period of 3 hours. The reaction was allowed to stir for 10 hours. After 10 hours a separating funnel separated the organic layer of the reaction mixture. The aqueous layer was extracted with 4×20 mL diethyl ether. The combined organic layer was distilled to yield styrene oxide. The conversion to epoxide is 99% with selectivity 92%.
Reaction SMILES: [CH3:1][C:2]1[C:3]2[CH:4]=[C:5]([OH:35])[CH:6]=[CH:7][C:8]=2[N:9]([CH2:18][C:19]2[CH:20]=[CH:21][C:22]([O:25][CH2:26][CH2:27][N:28]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)=[CH:23][CH:24]=2)[C:10]=1[C:11]1[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=1.C[OH:37]>C(O)(C)C>[CH3:1][C:2]1[C:3]2[CH:4]=[C:5]([OH:35])[CH:6]=[CH:7][C:8]=2[N:9]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][N:28]3[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]3)=[CH:21][CH:20]=2)[C:10]=1[C:11]1[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=1.[CH3:27][C:26]([OH:37])=[O:25]
Reactant: CO
Agent: Cc1c(-c2ccc(O)cc2)n(Cc2ccc(OCCN3CCCCCC3)cc2)c2ccc(O)cc12
Solvent: CC(C)O
Product: CC(=O)O
Temperature: 27.5 °C

Procedure:
Crystalline bazedoxifene free base (15 g) is charged in a mixture of methanol (180 mL) and isopropyl alcohol (120 mL) and heated to reflux temperature to make a clear solution. The solution is filtered and cooled to about 25-30° C. over a period of 15 minutes followed by addition of acetic acid (1.91 g) and then seed crystals of Form D (0.75 g). Then the mixture is maintained at same temperature for about 20 minutes and then allowed to cool to 0° C. over a period of about 30 minutes. The solid is collected by filtration and dried under vacuum at about 80° C. for about 5 hours to afford the title compound having HPLC Purity of 99.80%. The obtained sample is analyzed by Scanning Electron Microscope and the image is depicted in FIG. 8.
Reaction SMILES: [I-].[C:2]([CH:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH:6]1[OH:18])(=[NH:4])[NH2:3].C[OH:20]>C([O-])(=O)C.[Ag+]>[C:14]([OH:20])(=[O:13])[CH3:17].[C:2]([CH:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:16])([CH3:15])[CH3:17])=[O:12])[CH2:7][CH:6]1[OH:18])(=[NH:3])[NH2:4]
Reactant: CO
Agent: [Ag+]
Agent: CC(=O)[O-]
Agent: CC(C)(C)OC(=O)N1CCC(C(=N)N)C(O)C1
Product: CC(=O)O

Procedure:
A solution of 2.76 g (7.09 mmol) of (3RS,4SR)-[amino-(1-tert-butoxycarbonyl-3-hydroxy-piperidine-4-yl)-methylene-methyl-sulphonium iodide in 15 ml of methanol was treated with 0.41g (3.55 mmol) of ammonium carbonate and stirred at room temperature for 18 hours. For the working-up, the reaction mixture was evaporated under reduced pressure. 2.5 g (95% of theory) of tert-butyl (3RS,4RS)-4-carbamimidoyl-3-hydroxy-piperidine-1-carboxylate iodide were obtained as a colourless foam. A solution of 715 mg (1.92 mmol) of tert-butyl (3RS,4RS)-4-carbamimidoyl-3-hydroxy-piperidine-1-carboxylate iodide in 20 ml of methanol was stirred at room temperature for 1 hours with 321 mg (1.92 mmol) of silver acetate. The precipitated silver iodide was filtered off and washed with 20 ml of methanol. The light yellow filtrate obtained was evaporated under reduced pressure. There were obtained 538 mg (92% of theory) of tert-butyl (3RS,4RS)-4-carbamimidoyl-3-hydroxy-piperidine-1-carboxylate acetate as a colourless foam.
Reaction SMILES: C([Li])CCC.[CH3:6][C:7]1[C:11]([CH3:12])=[CH:10][S:9][CH:8]=1.CN([CH:16]=[O:17])C.Cl>CCOCC.C1COCC1>[CH:16]([C:8]1[S:9][CH:10]=[C:11]([CH3:12])[C:7]=1[CH3:6])=[O:17]
Reactant: CN(C)C=O
Reactant: Cc1cscc1C
Agent: Cl
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: C1CCOC1
Product: Cc1csc(C=O)c1C
Temperature: 25 °C
Yield: 56 %

Procedure:
A solution of 1.5 M n-butyllithium (3.4 mL, 5.1 mmol) in ether was added dropwise under argon to a solution of 3,4-dimethylthiophene trimer (1.62 g, 4.8 mmol, See Example 16) in dry THF (10 mL) at −70° C. and the resultant solution was warmed to −50° C. Next, 0.4 mL (5.4 mmol) of DMF was added dropwise and the mixture allowed to warm to room temperature overnight. The mixture was poured into a mixture of 1 liter of 12 M HCl and crushed in certain embodiments and thereafter extracted with ether. The organic layers were combined, washed with water, and dried over MgSO4. After evaporation of the solvent, the residue was purified by column chromatography (silica gel, hexane/CH2Cl2 (v:v) 3:1) to give the product 2-formyl-3,4-dimethylthiophene as a yellow solid (0.98 g, 56%) and recovered unreacted trimer (0.55 g). 1H NMR (CDCl3) δ 10.08 (1H, s, CHO), 6.99 (1H, s, aromatic H), 2.53 (3H, s, CH3), 2.22 (3H, s, CH3), 2.16 (3H, s, CH3), 2.13 (3H, s, CH3), 2.10 (6H, s CH3).
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17](=[O:19])[CH3:18])=[CH:12][CH:11]=2)[C:5]([C:20]#[N:21])=[C:4]([S:22]C2C=CC=CC=2)[N:3]=1.[S-2].[Na+].[Na+].Cl>CN(C=O)C>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:19])[CH3:18])=[CH:14][CH:15]=2)[C:5]([C:20]#[N:21])=[C:4]([SH:22])[N:3]=1
Reactant: CC(=O)Nc1ccc(-c2c(C#N)c(N)nc(Sc3ccccc3)c2C#N)cc1
Agent: Cl
Agent: [Na+]
Agent: [S-2]
Solvent: CN(C)C=O
Product: CC(=O)Nc1ccc(-c2c(C#N)c(N)nc(S)c2C#N)cc1
Temperature: 80 °C
Reaction time: 2 h

Procedure:
Under argon, 1.16 g (3 mmol) of N-{4-[2-amino-3,5-dicyano-6-(phenylsulfanyl)-4-pyridinyl]phenyl}-acetamide are dissolved in 10 ml of DMF, 0.78 g (10 mmol) of sodium sulfide are added and the mixture is stirred at 80° C. for 2 h. 20 ml of 1N HCl are then added and the resulting crystals are filtered off with suction and dried under reduced pressure.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[Li]CCCC.CN([CH:17]=[O:18])C>C1(C)C=CC=CC=1>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([CH:17]=[O:18])=[N:3][CH:4]=1
Reactant: CN(C)C=O
Reactant: Brc1ccc(Br)nc1
Agent: [Li]CCCC
Solvent: Cc1ccccc1
Product: O=Cc1ccc(Br)cn1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 31.3 %

Procedure:
A solution of 2,5-Dibromo-pyridine (22.2 g, 93.7 mmol, 1.0 equiv.) in toluene (1.2 L) was treated with nBuLi (70.25 ml, 112.4 mmol, 1.2 equiv.) dropwise at −78° C. The resulting solution was stirred at −78° C. for about 30 minutes, and DMF (11 ml, 141 mmol, 1.5 equiv.) was added. The reaction solution was warmed up gradually to RT and then stirred overnight. When TLC and MS showed the reaction was complete, the reaction mixture was concentrated in vacuo, and the residue was directly purified by column chromatography (SiO2, 10-30% EtOAc/Hexanes gradient elution) to afford 5-Bromo-pyridine-2-carbaldehyde (1038, 5.45 g, 31% yield) as yellowish white solid. For 1038: C6H4BrNO, LCMS (EI) m/e 187 (M++H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[Li]CCCC.CN([CH:17]=[O:18])C.[NH4+].[Cl-]>C1(C)C=CC=CC=1>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([CH:17]=[O:18])=[N:3][CH:4]=1
Reactant: CN(C)C=O
Reactant: Brc1ccc(Br)nc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: Cc1ccccc1
Product: O=Cc1ccc(Br)cn1
Temperature: -10 °C
Reaction time: 2 h

Procedure:
To a solution of 2,5-dibromopyridine (1 g) in toluene (50 mL) at −78° C. was slowly added 2.5M n-BuLi (2 mL). The reaction mixture was stirred for 2 h, then DMF (0.5 mL) was added. The solution was stirred for 1 h at −78° C., then warmed to −10° C. Saturated NH4Cl (10 mL) was added and the mixture was allowed to warm to room temperature. The two phases were partitioned and the organic layer dried over sodium sulfate and the solvent concentrated to dryness to afford 0.432 g of the title compound.
Reaction SMILES: [N+]([O-])(O)=O.[N+:5]([C:8]1[CH:9]=[C:10]([NH:14][C:15]([NH2:17])=[NH:16])[CH:11]=[CH:12][CH:13]=1)([O-:7])=[O:6].CN(C)[CH:20]=[CH:21][C:22]([C:24]1[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=1)=O.[OH-].[Na+]>C(O)(C)C>[N+:5]([C:8]1[CH:9]=[C:10]([NH:14][C:15]2[N:17]=[C:22]([C:24]3[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=3)[CH:21]=[CH:20][N:16]=2)[CH:11]=[CH:12][CH:13]=1)([O-:7])=[O:6]
Reactant: N=C(N)Nc1cccc([N+](=O)[O-])c1
Reactant: CN(C)C=CC(=O)c1cccnc1
Agent: [Na+]
Agent: [OH-]
Solvent: O=[N+]([O-])O
Solvent: CC(C)O
Product: O=[N+]([O-])c1cccc(Nc2nccc(-c3cccnc3)n2)c1
Reaction time: 0.5 h

Procedure:
41.3 g (0.17 mol) of 3-nitrophenyl-guanidine nitrate, made into a slurry in 50 ml of isopropanol, are added to a solution of 30 g (0.17 mol) of 3-dimethylamino-1-(3-pyridyl)-2-propen-1-one [described in EP-A-0 233 461] in 250 ml of isopropanol. After the addition of 7.49 g (0.19 mol) of sodium hydroxide, the yellow suspension is boiled at reflux for 8 hours. After cooling to 0°, the mixture is filtered and washed with 200 ml of isopropanol. The filtration residue is made into a sherry in 300 ml of water and stirred for 30 minutes, filtered and washed with 200 ml of water. After again making into a slurry in 200 ml of ethanol and washing with 200 ml of ethanol/diethyl ether (1:1) there is obtained N-(3-nitrophenyl)-4-(3-pyridyl)-2-pyrimidine-amine; m.p. 212°-213° , Rf =0.75 (chlorofoform:menthol=9:1).
Reaction SMILES: [O-2].[Hf+4:2].[O-2].[S:4](=[O:8])(=[O:7])([OH:6])[OH:5]>>[S:4]([O-:8])([O-:7])(=[O:6])=[O:5].[Hf+4:2].[S:4]([O-:8])([O-:7])(=[O:6])=[O:5]
Reactant: O=S(=O)(O)O
Agent: [Hf+4]
Agent: [O-2]
Product: O=S(=O)([O-])[O-]

Procedure:
After the unwanted hafnium oxide remaining in the bottoms of grooves 56a in the high dielectric film 52 on the wafer W reacts with the sulfuric acid to form hafnium sulfate, the wafer W is withdrawn from the hot concentrated sulfuric acid 62 in the treating tub 61. As shown in FIG. 7B, the wafer W is loaded into a cleaning tub 63 storing deionized water 64. The wafer W is immersed in the deionized water 64 in the cleaning tub 63. Though not shown, deionized water is continuously supplied to the cleaning tub 63 through an inlet port formed in a bottom thereof, and is overflowing an upper portion of the cleaning tub 63. By immersing the wafer W in the deionized water 64, the hafnium sulfate on the wafer W dissolves into the deionized water 64 to be removed from the wafer W.
Reaction SMILES: [S:1](=[O:5])(=[O:4])([OH:3])[OH:2].[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[CH2:19][CH:18]([CH2:20][CH:21]3[CH2:26][CH2:25][N:24]([CH2:27][C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH2:23][CH2:22]3)[C:16](=[O:17])[C:11]2=[CH:12][C:13]=1[O:14][CH3:15]>C(OCC)(=O)C>[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[CH2:19][CH:18]([CH2:20][CH:21]3[CH2:22][CH2:23][N:24]([CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[CH2:25][CH2:26]3)[C:16](=[O:17])[C:11]2=[CH:12][C:13]=1[O:14][CH3:15].[S:1]([O-:5])([O-:4])(=[O:3])=[O:2]
Reactant: O=S(=O)(O)O
Agent: COc1cc2c(cc1OC)C(=O)C(CC1CCN(Cc3ccccc3)CC1)C2
Solvent: CCOC(C)=O
Product: O=S(=O)([O-])[O-]
Temperature: 25 °C

Procedure:
Sulfuric acid (0.53 ml, dissolved in 35 ml of acetone) is slowly added to a solution of Donepezil (3.79 g) in ethyl acetate (70 ml) with stirring at room temperature. The solid precipitated is filtered and dried at 55° C. under vacuum to give the title compound.
Reaction SMILES: [S:1]([OH:5])([OH:4])(=[O:3])=[O:2].[NH2:6][C:7]([NH:9][C:10]([NH2:12])=[NH:11])=[NH:8].C[O-].[Na+:15].NC(NC(N)=N)=N>CO>[S:1]([O-:5])([O-:4])(=[O:3])=[O:2].[Na+:15].[Na+:15].[NH2:8][C:7]([NH:9][C:10]([NH2:12])=[NH:11])=[NH:6]
Reactant: O=S(=O)(O)O
Agent: C[O-]
Agent: N=C(N)NC(=N)N
Agent: [Na+]
Solvent: CO
Product: O=S(=O)([O-])[O-]

Procedure:
Biguanide was prepared fresh by refluxing anhydrous biguanide sulfate in a methanol solution of freshly prepared sodium methylate by the method of Slotta et al. (Slotta, K. H., Tschesche, R., Ber. Dtsch. Chem. Ges. 1929, B62, 1390-1398). The biguanide was used in solution as prepared for all of the reactions. Because sodium sulfate formed in the preparation of biguanide did not interfere with subsequent reactions, it was not necessary to separate it from the biguanide. Ethyl malonamate used in the preparation of Ib (see Example 1 below) was prepared as follows by methods of Galat and Marguery (Galat, A., J. Am. Chem. Soc. 1948, 70, 2596 and Marguery, M. F., Bull. Soc. Chem. France 1905, 33, 541; J. Recherces Centr. Natl. Recherche Sci., Labs. Bellevue (Paris) 1959, 47, 147), through Chem. Abstr. 1962, 56, 4744 g.): Diethyl malonate was converted to the mono-potassium salt of the half-ester. The latter was converted to ethyl malonyl chloride, which in turn was reacted with anhydrous ammonia in ice-cold ether to form ethyl malonamate.
Reaction SMILES: [C:1]([C:3]1[N:7]2[N:8]=[CH:9][CH:10]=[CH:11][C:6]2=[N:5][CH:4]=1)#[CH:2].[CH:12]1([C:15]2[CH:16]=[C:17]([NH:29][C:30](=[O:39])[C:31]3[CH:36]=[CH:35][C:34]([CH3:37])=[C:33](I)[CH:32]=3)[CH:18]=[CH:19][C:20]=2[CH2:21][N:22]2[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]2)[CH2:14][CH2:13]1>CO>[CH:12]1([C:15]2[CH:16]=[C:17]([NH:29][C:30](=[O:39])[C:31]3[CH:32]=[CH:33][C:34]([CH3:37])=[C:35]([C:2]#[C:1][C:3]4[N:7]5[N:8]=[CH:9][CH:10]=[CH:11][C:6]5=[N:5][CH:4]=4)[CH:36]=3)[CH:18]=[CH:19][C:20]=2[CH2:21][N:22]2[CH2:23][CH2:24][N:25]([CH3:28])[CH2:26][CH2:27]2)[CH2:14][CH2:13]1
Reactant: C#Cc1cnc2cccnn12
Reactant: Cc1ccc(C(=O)Nc2ccc(CN3CCN(C)CC3)c(C3CC3)c2)cc1I
Solvent: CO
Product: Cc1ccc(C(=O)Nc2ccc(CN3CCN(C)CC3)c(C3CC3)c2)cc1C#Cc1cnc2cccnn12

Procedure:
The title compound was synthesized from 3-ethynylimidazo[1,2-b]pyridazine and N-(3-cyclopropyl-4-((4-methylpiperazin-1-yl)methyl)phenyl)-3-iodo-4-methylbenzamide in a manner similar to that described for Example 14 (nitro reduction performed in a manner similar to that described for Example 17; 0.25M in MeOH/10% AcOH). The product was obtained as a solid: 505 m/z (M+H).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][N:27]=1)[C:5]([NH:7][C:8]1[S:9][C:10]2[C:16]([CH:17]3[CH2:22][O:21][CH2:20][CH2:19][O:18]3)=[CH:15][CH:14]=[C:13]([O:23][CH3:24])[C:11]=2[N:12]=1)=[O:6].C(=O)([O-])[O-].[Cs+].[Cs+].[NH:34]1[CH2:37][CH2:36][CH2:35]1>>[N:34]1([C:2]2[CH:3]=[C:4]([CH:25]=[CH:26][N:27]=2)[C:5]([NH:7][C:8]2[S:9][C:10]3[C:16]([CH:17]4[CH2:22][O:21][CH2:20][CH2:19][O:18]4)=[CH:15][CH:14]=[C:13]([O:23][CH3:24])[C:11]=3[N:12]=2)=[O:6])[CH2:37][CH2:36][CH2:35]1
Reactant: C1CNC1
Reactant: COc1ccc(C2COCCO2)c2sc(NC(=O)c3ccnc(Br)c3)nc12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Product: COc1ccc(C2COCCO2)c2sc(NC(=O)c3ccnc(N4CCC4)c3)nc12

Procedure:
From (±)-2-bromo-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-isonicotinamide with cesium carbonate and azetidine. ES-MS m/e (%): 427 (M+H+, 100).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[N:10]([O-])=O.[Na+].O.O.[Sn](Cl)Cl>Cl.O>[NH:1]([C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1)[NH2:10]
Reactant: COc1ccc(N)cn1
Reactant: O=N[O-]
Agent: Cl
Agent: Cl[Sn]Cl
Agent: [Na+]
Solvent: O
Product: COc1ccc(NN)cn1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
A solution of 5-amino-2-methoxy pyridine (1.0 g, 8.0 mmol) in 37% hydrochloric acid (7 mL) was cooled in an ice-salt bath and a solution of sodium nitrite (611 mg, 8.8 mmol) in water (2 mL) was added dropwise. The reaction mixture was stirred for 15 minutes then slowly added to an ice-cold solution of tin(II)chloride dihydrate (5.5 g, 24 mmol) in 37% hydrochloric acid (7 mL). After 3 hours at 0° C. the solids were collected by filtration and dissolved in 5% sodium hydroxide solution. The acidic, aqueous filtrate was carefully neutralized with 12M sodium hydroxide, then more base was added to raise the pH to about 12. The alkaline solutions were combined and extracted several times with ether. The extract was dried over sodium sulfate, filtered and concentrated to afford 5-hydrazino-2-methoxypyridine, and was used without further purification.
Reaction SMILES: [C:1]([C:4]1[CH:13]=[CH:12][C:11]([OH:14])=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8](=[O:15])[NH:9]2)(=[O:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH2:22](Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>CN(C)C=O>[C:1]([C:4]1[CH:13]=[CH:12][C:11]([O:14][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8](=[O:15])[NH:9]2)(=[O:3])[CH3:2]
Reactant: CC(=O)c1ccc(O)c2[nH]c(=O)ccc12
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(=O)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Temperature: 25 °C
Reaction time: 2 h
Yield: 87.4 %

Procedure:
5-Acetyl-8-hydroxy-1H-quinolin-2-one (430 g, 2.12 mol) was suspended in N,N-dimethylformamide (3.3 L), potassium carbonate (298 g, 2.16 mol) and subsequently benzyl bromide (298 g, 2.11 mol) were added thereto, and the mixture was stirred at room temperature for 2 hours. The insoluble matter was removed by filtration and washed with N,N-dimethylformamide. The filtrate and the washing were mixed and concentrated under reduced pressure. To the residue was added purified water (3.3 L) and the mixture was stirred at room temperature overnight. The precipitate was collected by filtration, washed with purified water, and dried under vacuum to obtain 5-acetyl-8-benzyloxy-1H-quinolin-2-one (541 g).
Reaction SMILES: [C:1]([C:4]1[CH:5]=[N:6][CH:7]=[C:8]([Br:10])[CH:9]=1)(=[O:3])[CH3:2].[CH3:11][Mg]Br.C(OCC)C>O1CCCC1>[Br:10][C:8]1[CH:9]=[C:4]([C:1]([OH:3])([CH3:11])[CH3:2])[CH:5]=[N:6][CH:7]=1
Reactant: CC(=O)c1cncc(Br)c1
Reactant: C[Mg]Br
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC(C)(O)c1cncc(Br)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a cooled (−78° C.) solution of 3-acetyl-5-bromo pyridine (1.98 g, 9.90 mmol) in tetrahydrofuran (33 mL) was added dropwise a solution of methyl magnesium bromide in diethyl ether (3.0 M, 6.60 mL, 19.8 mmol). The reaction was warmed to room temperature, and the resulting mixture was stirred at room temperature overnight. The reaction was then quenched with saturated aqueous ammonium chloride solution and extracted with diethyl ether. The organic extracts were combined, washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography on silica gel (0-60% ethyl acetate in hexanes) provided the title compound: LCMS m/z 217.83 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 8.61 (s, 1 H), 8.53 (s, 1 H), 8.01 (d, J=1.9 Hz, 1 H), 2.38 (br s, 1 H), 1.61 (6 H).
Reaction SMILES: [C:1]([C:5]([C:8]([C:11]([C:14]([C:17]([C:20]([C:23]([CH:26]=[CH2:27])([F:25])[F:24])([F:22])[F:21])([F:19])[F:18])([F:16])[F:15])([F:13])[F:12])([F:10])[F:9])([F:7])[F:6])([F:4])([F:3])[F:2].[Al](I)(I)[I:29].C(=O)=O.CC(C)=O>>[C:1]([C:5]([C:8]([C:11]([C:14]([C:17]([C:20]([C:23]([CH2:26][CH2:27][I:29])([F:24])[F:25])([F:21])[F:22])([F:18])[F:19])([F:16])[F:15])([F:13])[F:12])([F:10])[F:9])([F:7])[F:6])([F:4])([F:3])[F:2]
Reactant: C=CC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Reactant: I[Al](I)I
Agent: O=C=O
Solvent: CC(C)=O
Product: FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)CCI
Temperature: 130 °C
Reaction time: 2 h

Procedure:
198 g of CF3(CF2)7CH═CH2 and 5 g of AlI3 were charged into a 200-ml stainless-steel autoclave and displacement of the atmosphere with nitrogen was repeated 5 times by vacuum evacuation and charging with nitrogen gas while cooling the autoclave with dry ice/acetone. The oxygen concentration inside the system was not more than 1 ppm and the moisture content was not more than 1 ppm. Thereafter, nitrogen was removed by evacuation and 11 g of hydrogen iodide gas was charged therein. Heating was carried out with stirring for two hours at 130° C. After cooling, the liquid in the autoclave was sampled, and GC analysis (gas chromatography analysis) and GC/MS analysis (gas chromatography/mass analysis) were performed. CF3(CF2)7CH2CH2I was produced at a conversion rate of 2% and at a selectivity of 100%.
Reaction SMILES: [OH:1][CH2:2][C:3]#[CH:4].[O:5]1[CH:10]=[CH:9][CH2:8][CH2:7][CH2:6]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(Cl)Cl>[O:5]1[CH2:6][CH2:7][CH2:8][CH2:9][CH:10]1[O:1][CH2:2][C:3]#[CH:4]
Reactant: C1=COCCC1
Reactant: C#CCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Product: C#CCOC1CCCCO1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a stirred solution of 112 g. (2.0 mol.) of 3-hydroxy-1-propyne and 260 g. (3.0 mol.), of dihydropyran in 1.20 l. of methylene chloride cooled to 0° C. in an ice bath, is added a solution of 20 mg. of para-toluenesulfonic acid in 100 ml. of methylene chloride, dropwise. The reaction mixture is stirred at 0° C. for one-half hour, and at ambient temperature for one hour. It is then poured into 200 ml. of a 5% solution of sodium bicarbonate, the organic phase is separated, the aqueous phase extracted with 100 ml. of methylene chloride, the combined organic phases washed with 100 ml. of a solution of brine, dried over sodium sulfate, and evaporated under vacuum (12 mm.) at 45° C., to give 300 g. of crude product, which is purified by fractional distillation, b,p, 71°-73° C. (14 mm.) to yield 250 g. (89%) of a liquid.