Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I.CS[C:4](=[N:19][CH3:20])[NH:5][C:6]1[CH:11]=[C:10]([CH3:12])[CH:9]=[CH:8][C:7]=1[N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.[CH2:21]([NH2:25])[CH2:22][CH2:23][CH3:24].O.O.O.C([O-])(=O)C.[Pb+2].C([O-])(=O)C>C(O)C>[CH2:21]([NH:25][C:4]([NH:19][CH3:20])=[N:5][C:6]1[CH:11]=[C:10]([CH3:12])[CH:9]=[CH:8][C:7]=1[N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)[CH2:22][CH2:23][CH3:24]
Reactant: CN=C(Nc1cc(C)ccc1N1CCOCC1)SC
Reactant: CCCCN
Agent: CC(=O)[O-]
Agent: I
Agent: [Pb+2]
Solvent: CCO
Solvent: O
Product: CCCCNC(=Nc1cc(C)ccc1N1CCOCC1)NC

Procedure:
A mixture of 2-methyl-1-(5-methyl-2-morpholinophenyl)-3-methyl-2-thiopseudourea hydroiodide (12.2 g prepared as described in Example 227), n-butylamine (2.4 g) and ethanol (80 ml) was stored at ambient temperature for 4 months. Lead acetate trihydrate (9 g) was then added and the mixture heated under reflux for one hour to yield 1-(n-butyl)-2-(5-methyl-2-morpholinophenyl)-3-methylguanidine which was converted into its monofumarate salt (m.p. 150° C.) which was recrystallised from a 1:2 mixture of methanol and ether.
Reaction SMILES: [Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13](O)=[O:14])=[CH:11][C:10]([C:16]([F:19])([F:18])[F:17])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C([Cl:23])=O>ClCCl.CN(C=O)C>[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]([Cl:23])=[O:14])=[CH:11][C:10]([C:16]([F:19])([F:18])[F:17])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)c1cc(C(F)(F)F)nn1-c1ncccc1Cl
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Cl)c1cc(C(F)(F)F)nn1-c1ncccc1Cl
Reaction time: 1 h

Procedure:
To a solution of 268 mg (0.92 mmol) of 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid (which can be prepared according to Example 6) in 5 mL of dichloromethane was added 160 μL (1.84 mmol) of oxalyl chloride and two drops of DMF in sequence at room temperature. The mixture was then stirred at the same temperature for about 1 hour. The crude mixture was then concentrated in vacuo. The title material is typically used without additional purification or characterization.
Reaction SMILES: C([O:8][CH2:9][CH2:10][C@H:11]([NH:28][C:29]1[N:37]=[CH:36][N:35]=[C:34]2[C:30]=1[NH:31][CH:32]=[N:33]2)[C:12]1[N:16]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[C:15]2[CH:23]=[C:24]([F:27])[CH:25]=[CH:26][C:14]=2[N:13]=1)C1C=CC=CC=1.B(Br)(Br)Br.CO>C(Cl)Cl>[F:27][C:24]1[CH:25]=[CH:26][C:14]2[N:13]=[C:12]([C@@H:11]([NH:28][C:29]3[N:37]=[CH:36][N:35]=[C:34]4[C:30]=3[N:31]=[CH:32][NH:33]4)[CH2:10][CH2:9][OH:8])[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[C:15]=2[CH:23]=1
Reactant: Fc1ccc2nc([C@H](CCOCc3ccccc3)Nc3ncnc4nc[nH]c34)n(-c3ccccn3)c2c1
Agent: BrB(Br)Br
Solvent: ClCCl
Solvent: CO
Product: OCC[C@H](Nc1ncnc2[nH]cnc12)c1nc2ccc(F)cc2n1-c1ccccn1
Temperature: 0 °C
Reaction time: 1 h
Yield: 44.2 %

Procedure:
To a solution of [(S)-3-benzyloxy-1-(6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)propyl](7H-purin-6-yl)amine (465 mg, 0.8 mmol) in anhydrous DCM (8 mL) at 0° C. under a nitrogen atmosphere was added dropwise boron tribromide (1.0 M in DCM, 2.4 mL, 2.4 mmol). The reaction mixture was stirred at 0° C. for 1 h. MeOH was added and the volatiles removed under reduced pressure. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-15% MeOH in DCM) to afford 304 as a white solid (143 mg, 44%). LCMS (Method K): RT 2.73 min [M+H]+ 404.9. 1H NMR (DMSO-d6, 400 MHz): δ 9.56-9.48 (1H, m), 8.65-8.57 (2H, m), 8.49 (1H, s), 8.11 (1H, td, J=7.74, 1.90 Hz), 7.83-7.74 (2H, m), 7.56 (1H, t, J=6.09 Hz), 7.28-7.16 (2H, m), 6.07-5.97 (1H, m), 3.59-3.45 (2H, m), 2.39-2.29 (1H, m), 2.24-2.12 (1H, m)
Reaction SMILES: [CH3:1][CH:2]([CH3:20])[C:3]([NH:5][C:6]1[CH:16]=[CH:15][C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:8][C:7]=1[N+:17]([O-])=O)=[O:4].CCCCCC.C(OCC)(=O)C>C(O)C.[Pt]=O>[NH2:17][C:7]1[CH:8]=[C:9]([CH:15]=[CH:16][C:6]=1[NH:5][C:3](=[O:4])[CH:2]([CH3:20])[CH3:1])[C:10]([O:12][CH2:13][CH3:14])=[O:11]
Reactant: CCOC(=O)c1ccc(NC(=O)C(C)C)c([N+](=O)[O-])c1
Agent: O=[Pt]
Solvent: CCOC(C)=O
Solvent: CCO
Solvent: CCCCCC
Product: CCOC(=O)c1ccc(NC(=O)C(C)C)c(N)c1
Reaction time: 2 h
Yield: 69.8 %

Procedure:
A sample of ethyl 4-(2-methylpropionylamino)-3-nitrobenzoate (8.0 g, 0.0286 mol) was suspended in ethanol (75 mL) containing platinum oxide (50 mg). The reaction mixture was hydrogenated for 2 h at 35 psi. Thin-layer chromatographic analysis (SiO2, 1:1 hexane:ethyl acetate) showed disappearance of starting material along with the formation of a new lower-running spot (Rf =0.2). The mixture was then filtered through a pad of Celite and the pad washed with fresh ethanol. The filtrate was concentrated and the residue recrystallized from ethyl acetate-hexane. The solid was collected by filtration to give 5.0 g (70%) of ethyl 3-amino-4-(2-methylpropionylamino)benzoate. An analytical sample was prepared by recrystallization twice from ethyl acetate-hexane. The residue was collected by filtration and then dried in vacuo at acetone reflux to give a beige solid, mp 147°-149° C.
Reaction SMILES: C(C1OC1)Cl.[CH2:6]([O:10][C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]=1[CH:21]=[N:22][OH:23])[CH:7]1[O:9][CH2:8]1.ClN1C(=O)CCC1=O.C(N(CC)CC)C>C(Cl)(Cl)Cl>[CH2:6]([O:10][C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]=1[C:21]#[N+:22][O-:23])[CH:7]1[O:9][CH2:8]1
Reactant: ON=Cc1c(OCC2CO2)ccc2ccccc12
Agent: O=C1CCC(=O)N1Cl
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Solvent: ClCC1CO1
Product: [O-][N+]#Cc1c(OCC2CO2)ccc2ccccc12
Yield: 79 %

Procedure:
As shown in Chemical Formula 2, 3.00 g (12.3 mmol) of 2-(glycidyloxy)-1-naphthoaldehyde oxime (4) was dissolved in 66 mL of chloroform in an ice bath and thereto, 1.84 g (13.5 mmol) of N-chlorosuccinimide (NCS) was added. While stirring the resultant reaction mixture, 1.63 mL (16.0 mmol) of triethylamine was added to the reaction mixture, followed by stirring the resultant reaction mixture for 6 hours to effect the reaction. Then, the reaction solution was washed with each of 50 mL of pure water and 50 mL of Brine three times, and the organic phase was dried over MgSO4, followed by concentrating the solvent under reduced pressure to obtain 2-(glycidyloxy)-1-naphthonitrile oxide B with a yield of 79%.
Reaction SMILES: [C:1]([CH2:4][CH2:5][NH:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]([CH3:18])[C:14]([O:16][CH3:17])=[O:15])=[CH:9][C:8]=1[Cl:19])([OH:3])=O.[OH-].[Na+]>C1(C)C=CC=CC=1>[Cl:19][C:8]1[CH:9]=[C:10]([CH:13]([CH3:18])[C:14]([O:16][CH3:17])=[O:15])[CH:11]=[C:12]2[C:7]=1[NH:6][CH2:5][CH2:4][C:1]2=[O:3]
Reactant: COC(=O)C(C)c1ccc(NCCC(=O)O)c(Cl)c1
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Product: COC(=O)C(C)c1cc(Cl)c2c(c1)C(=O)CCN2
Temperature: 100 °C

Procedure:
Further, the suspension of 80 g of polyphosphoric acid and 80 ml of toluene was stirred at 100° C., 20 ml of toluene solution of above-mentioned compound (methyl 2-[4-(2-carboxyethylamino)-3-chlorophenyl]propionate) were added thereto and stirred for further 1 hour. After cooling, ice-water was added to the reaction mixture, then the mixture was poured into an aqueous solution of sodium hydroxide to adjust the pH to 9 to 10, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was subjected to column chromatography on silica gel, eluted with a mixture of ether and hexane to give 6.4 g of methyl 2-(8-chloro-1,2,3,4-tetrahydro-4-oxoquinolin-6-yl)propionate (Compound 32).
Reaction SMILES: [F:1][CH:2]([F:21])[C:3]1[C:8]([C:9]([O:11]CC)=[O:10])=[CH:7][C:6]([CH2:14][NH:15][C:16](=[O:20])[CH:17]([CH3:19])[CH3:18])=[CH:5][N:4]=1.O.[OH-].[Li+].Cl>O1CCOCC1>[F:21][CH:2]([F:1])[C:3]1[C:8]([C:9]([OH:11])=[O:10])=[CH:7][C:6]([CH2:14][NH:15][C:16](=[O:20])[CH:17]([CH3:19])[CH3:18])=[CH:5][N:4]=1
Reactant: CCOC(=O)c1cc(CNC(=O)C(C)C)cnc1C(F)F
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: CC(C)C(=O)NCc1cnc(C(F)F)c(C(=O)O)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 94.7 %

Procedure:
Dissolve ethyl 2-(difluoromethyl)-5-{[(2-methylpropanoyl)amino]methyl}pyridine-3-carboxylate (414 g, 1.38 mol, 1.0 equiv) in 1,4-dioxane (4.97 L). Add water (2.48 L) and lithium hydroxide (125.6 g, 2.96 mol, 2.5 equiv); then stir the resulting mixture for 60 min at room temperature. Concentrate the 1,4-dioxane solution to ½ volume under reduced pressure, and add hydrochloric acid (5 N, 1.16 L, 5.79 mol, 4.2 equiv) slowly to maintain temperature at less than 20° C. until the pH is 2. Collect the solids by filtration; air dry for 18 hours; and then in a vacuum oven at 40° C. for 18 hours to give a white solid, (355.4 g, 94.7% yield). MS (m/z) 303 (M+1).
Reaction SMILES: [F:1][C:2]([F:24])([F:23])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:22]=[CH:21][C:18]([CH:19]=O)=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.[CH2:25]([NH:32][C:33](=[S:36])[NH:34][NH2:35])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.O>CCO>[CH2:25]([NH:32][C:33]([NH:34][N:35]=[CH:19][C:18]1[CH:21]=[CH:22][C:15]([C:12]2[N:13]=[CH:14][N:10]([C:7]3[CH:8]=[CH:9][C:4]([O:3][C:2]([F:24])([F:23])[F:1])=[CH:5][CH:6]=3)[N:11]=2)=[CH:16][CH:17]=1)=[S:36])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: NNC(=S)NCc1ccccc1
Reactant: O=Cc1ccc(-c2ncn(-c3ccc(OC(F)(F)F)cc3)n2)cc1
Solvent: CCO
Solvent: O
Product: FC(F)(F)Oc1ccc(-n2cnc(-c3ccc(C=NNC(=S)NCc4ccccc4)cc3)n2)cc1
Temperature: 80 °C

Procedure:
To a 50 mL round-bottomed flask containing 4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]benzaldehyde (500 mg, 1.5 mmol) in EtOH (3 mL) was added 4-benzylthiosemicarbazide (650 mg, 3.6 mmol). The reaction mixture was heated at 80° C. overnight. H2O was added upon completion of the reaction and the crude product material was isolated by vacuum filtration. The title compound was isolated via RP-HPLC as a white solid (390 mg, 52% yield): mp 220-224° C.; 1H NMR (400 MHz, CDCl3) δ 9.29 (s, 1H), 8.59 (s, 1H), 8.21 (d, J=8.4 Hz, 2H), 7.85-7.79 (m, 3H), 7.71 (d, J=8.4 Hz, 2H), 7.46-7.30 (m, 8H), 5.01 (d, J=5.8 Hz, 2H); ESIMS 497.2 (M+H).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][C:4](=[O:7])[CH2:3][CH2:2]1.C(N(CC)CC)C.[Cl-].[CH2:16]([N:18]([CH2:22][CH3:23])[C:19](=[O:21])C)[CH3:17]>CN(C=O)C>[CH2:16]([N:18]([CH2:22][CH3:23])[C:19]([N:1]1[CH2:6][CH2:5][C:4](=[O:7])[CH2:3][CH2:2]1)=[O:21])[CH3:17]
Reactant: O=C1CCNCC1
Reactant: CCN(CC)C(C)=O
Agent: [Cl-]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCN(CC)C(=O)N1CCC(=O)CC1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To a solution of piperidin-4-one in DMF was added triethylamine (1.5 eq.) and N,N-diethylacetamide chloride (1.5 eq.). The resulting solution was stirred at room temperature for 5 hours or until completion observed by TLC. The solvent was evaporated and the residue was partitioned in H2O and EtOAc. The aqueous layer was extracted with EtOAc and the combined organic layers were dried over Na2SO4 and concentrated. The crude product was purified by a CombiFlash chromatography system using silica gel cartridge and CH2Cl2/MeOH gradient eluent to afford 4-oxo-piperidine-1-carboxylic acid diethylamide, which was subsequently reacted with 3-hydroxybenzaldehyde (2.5 eq.) in acetic acid (99.7%) and purged with HCl gas (0.5-1 h). After stirring at room temperature for 3 hours, the solvent was evaporated and the crude was purified by a Combiflash chromatography system with hexanes/EtOAc as eluent, followed by crystallization from MeOH, to afford Compound 12 as a yellow crystalline solid.
Reaction SMILES: [F:1][CH:2]([F:24])[C:3]1[N:8]2[N:9]=[CH:10][C:11]([C:12]#[CH:13])=[C:7]2[N:6]=[C:5]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[CH:4]=1.Br[C:26]1[CH:27]=[CH:28][C:29]([CH3:39])=[C:30]([S:32]([NH:35][CH2:36][CH2:37][OH:38])(=[O:34])=[O:33])[CH:31]=1>>[F:24][CH:2]([F:1])[C:3]1[N:8]2[N:9]=[CH:10][C:11]([C:12]#[C:13][C:26]3[CH:27]=[CH:28][C:29]([CH3:39])=[C:30]([S:32]([NH:35][CH2:36][CH2:37][OH:38])(=[O:34])=[O:33])[CH:31]=3)=[C:7]2[N:6]=[C:5]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[CH:4]=1
Reactant: Cc1ccc(Br)cc1S(=O)(=O)NCCO
Reactant: C#Cc1cnn2c(C(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12
Product: Cc1ccc(C#Cc2cnn3c(C(F)F)cc(-c4ccc(C(F)(F)F)cc4)nc23)cc1S(=O)(=O)NCCO

Procedure:
The title compound was prepared from 7-Difluoromethyl-3-ethynyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (example C.2) (340 mg, 1.0 mmol) and 5-bromo-N-(2-hydroxy-ethyl)-2-methyl-benzenesulfonamide (example B.17) (267 mg, 1.0 mmol) according to general procedure II. Obtained as a yellow solid (230 mg, 41%). MS (ISP) 551.3[(M+H)+]; mp 184-186° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:24]CC2C=CC(OC)=CC=2)=[C:6]([C:8]2[N:12]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:11]=[CH:10][C:9]=2[N+:21]([O-:23])=[O:22])[CH:7]=1.O.C(=O)(O)[O-].[Na+]>ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:24])=[C:6]([C:8]2[N:12]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:18])([CH3:19])[CH3:20])[N:11]=[CH:10][C:9]=2[N+:21]([O-:23])=[O:22])[CH:7]=1
Reactant: COc1ccc(COc2ccc(Cl)cc2-c2c([N+](=O)[O-])cnn2COCC[Si](C)(C)C)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: C[Si](C)(C)CCOCn1ncc([N+](=O)[O-])c1-c1cc(Cl)ccc1O
Temperature: 25 °C
Reaction time: 48 h
Yield: 83 %

Procedure:
To a solution of 5-(5-chloro-2-(4-methoxybenzyloxy)phenyl)-4-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (prepared according to the procedure described for Example 14) (1.193 g, 2.434 mmol) in 17 mL dichloromethane was added 3 mL water followed by dichlorodicyanoquinone (1.2208 g). The reaction was stirred at room temperature for 48 hours, and then additional Dichlorodicyanoquinone (0.4946 g) was added. After an additional 24 hours, the reaction was poured into saturated aqueous sodium bicarbonate and extracted with dichloromethane. The organic portion was dried over magnesium sulfate and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (0 to 35% ethyl acetate in heptanes) to yield 745.2 mg (83%) of 4-chloro-2-(4-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)phenol. LCMS (ESI) m+H=270.2; 1H NMR (400 MHz, DMSO-d6) δ: 10.47 (s, 1H), 8.44 (s, 1H), 7.47 (d, J=2.6, 1H), 7.43 (dd, J=8.8, 2.7, 1H), 7.00 (d, J=8.8, 1H), 5.30 (dd, J=65.1, 10.8, 2H), 3.42 (t, J=8.1, 2H), 0.74 (t, 2H), −0.08 (s, 9H).
Reaction SMILES: [CH3:1][N:2]([C:6]1[C:11]([C:12]2[CH:13]=[CH:14][C:15]3[C:16]4[N:30](C5CCCCO5)[N:29]=[CH:28][C:17]=4[C:18](=[O:27])[N:19]([CH2:22][C:23]([F:26])([F:25])[F:24])[C:20]=3[CH:21]=2)=[CH:10][CH:9]=[CH:8][N:7]=1)[C:3](=[O:5])[CH3:4].CN(C1C(C2C=CC3C4NN(C5CCCCO5)CC=4C(=O)N(CC(F)(F)F)C=3C=2)=CC=CN=1)C(=O)C.[ClH:73]>O>[ClH:73].[CH3:1][N:2]([C:6]1[C:11]([C:12]2[CH:13]=[CH:14][C:15]3[C:16]4[NH:30][N:29]=[CH:28][C:17]=4[C:18](=[O:27])[N:19]([CH2:22][C:23]([F:26])([F:25])[F:24])[C:20]=3[CH:21]=2)=[CH:10][CH:9]=[CH:8][N:7]=1)[C:3](=[O:5])[CH3:4]
Reactant: CC(=O)N(C)c1ncccc1-c1ccc2c3c(cnn3C3CCCCO3)c(=O)n(CC(F)(F)F)c2c1
Agent: CC(=O)N(C)c1ncccc1-c1ccc2c3c(c(=O)n(CC(F)(F)F)c2c1)CN(C1CCCCO1)N3
Agent: Cl
Solvent: O
Product: CC(=O)N(C)c1ncccc1-c1ccc2c3[nH]ncc3c(=O)n(CC(F)(F)F)c2c1
Yield: 58 %

Procedure:
The product is obtained according to the procedure described in Step 1.7. starting with N-methyl-N-{3-[4-oxo-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}acetamide and N-methyl-N-{3-[4-oxo-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}acetamide, in the form of a white powder (hydrochloride, 1 H2O; yield 58%).
Reaction SMILES: Br[CH2:2][CH:3]([OH:13])[CH2:4][N:5]1[CH:10]=[C:9]([Cl:11])[CH:8]=[N:7][C:6]1=[O:12]>O1CCCC1>[Cl:11][C:9]1[CH:8]=[N:7][C:6](=[O:12])[N:5]([CH2:4][CH:3]2[O:13][CH2:2]2)[CH:10]=1
Reactant: O=c1ncc(Cl)cn1CC(O)CBr
Solvent: C1CCOC1
Product: O=c1ncc(Cl)cn1CC1CO1
Temperature: 25 °C
Yield: 12.6 %

Procedure:
Aqueous M-sodium hydroxide solution (2.5 ml) was added to a stirred solution of 1-(3-bromo-2-hydroxypropyl)-5-chloropyrimidin-2-one (669 mg) in tetrahydrofuran (50 ml) and the mixture was stirred at room temperature. After 1 h the reaction mixture was evaporated to a yellow solid which was subjected to column chromatography on silica developing and eluting with chloroform-ethanol, 19:1. This gave a white crystalline solid which was recrystallised from ethyl acetate to give white crystals of the title pyrimidinone (59 mg), m.p. 132°-135° C., λmax (EtOH) 227 nm (E11 522), 332.5 nm (E11 160).
Reaction SMILES: [C:1]([CH:4]1[C:9](=[O:10])[CH2:8][CH2:7][CH2:6][C:5]1=O)(=O)[CH3:2].[NH2:12][NH2:13]>CO>[CH3:2][C:1]1[C:4]2[C:9](=[O:10])[CH2:8][CH2:7][CH2:6][C:5]=2[NH:13][N:12]=1
Reactant: CC(=O)C1C(=O)CCCC1=O
Reactant: NN
Solvent: CO
Product: Cc1n[nH]c2c1C(=O)CCC2
Temperature: 0 °C

Procedure:
To an ice-cold solution of 33.3 grams of 2-acetyl-1,3-cyclohexanedione in 400 ml of methanol was added dropwise a solution of 7.2 ml of hydrazine in 50 ml of methanol and the resulting reaction mixture was heated at reflux for 20 hours. The solvent was then removed under reduced pressure and the residue was triturated in ethyl ether to give 1,5,6,7-tetrahydro-3-methyl-4H-indazol-4-one as a yellow crystalline solid melting at about 154°-157° C.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]#[N:15])=[CH:10][CH:9]=2)=[CH:4][C:3]=1[CH3:16].[I:17]N1C(=O)CCC1=O.CN(C)C(=N)N(C)C.[O-]S([O-])=O.[Na+].[Na+].C([O-])([O-])=O.[Na+].[Na+].P([O-])(O)(O)=O.[K+]>CCOCC.CN(C=O)C>[OH:1][C:2]1[C:7]([I:17])=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]#[N:15])=[CH:10][CH:9]=2)=[CH:4][C:3]=1[CH3:16]
Reactant: O=C1CCC(=O)N1I
Reactant: Cc1cc(-c2ccc(C#N)cc2)ccc1O
Agent: CN(C)C(=N)N(C)C
Agent: O=C([O-])[O-]
Agent: O=P([O-])(O)O
Solvent: CCOCC
Solvent: CN(C)C=O
Product: Cc1cc(-c2ccc(C#N)cc2)cc(I)c1O
Temperature: 25 °C
Reaction time: 96 h
Yield: 17 %

Procedure:
4′-hydroxy-3′-methyl-1,1′-biphenyl-4-carbonitrile (875 mg, 4.18 mmol) was dissolved into DMF (20 mL) and treated with N-iodosuccinimide (1.012 g, 4.5 mmol). The solution was stirred at room temperature for four days. Then the mixture was stirred with tetramethylguanidine (1 mL) for ten minutes, poured into an aqueous mixture of Na2SO3 and Na2CO3, adjusted to pH 9 with aqueous potassium dihydrogen phosphate, and diluted with ether. The gum which separated from the biphasic mixture was dissolved into EtOAc and added to a rapidly stirred mixture of the aqueous phase and ether. The organic phase was separated, filtered, combined with the original ethereal phase, concentrated, and chromatographed through silica with a 50% to 100% gradient of CH2Cl2/hexanes to provide the title compound as an off-white powder (17% yield). MS (ESI APCI negative ion detection) m/z 334 (M−H)−; 1HNMR (300 MHz, CDCl3) δ 2.38 (s, 3H), 7.26 (s, 1H), 7.33 (d, 1H), 7.60 (d, 2H), 7.66-7.74 (m, 3H).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([NH:7][S:8]([C:11]2[C:16]([Cl:17])=[CH:15][CH:14]=[C:13]([N+:18]([O-:20])=[O:19])[C:12]=2Cl)(=[O:10])=[O:9])=[CH:3][CH:2]=1.[H-].[Na+].[OH2:24]>>[N:1]1[CH:6]=[CH:5][C:4]([NH:7][S:8]([C:11]2[C:16]([Cl:17])=[CH:15][CH:14]=[C:13]([N+:18]([O-:20])=[O:19])[C:12]=2[OH:24])(=[O:10])=[O:9])=[CH:3][CH:2]=1
Reactant: O
Reactant: O=[N+]([O-])c1ccc(Cl)c(S(=O)(=O)Nc2ccncc2)c1Cl
Agent: [H-]
Agent: [Na+]
Product: O=[N+]([O-])c1ccc(Cl)c(S(=O)(=O)Nc2ccncc2)c1O
Yield: 33.3 %

Procedure:
Following the general hydrolysis procedure outlined in example 15, N-(4-pyridinyl)-2,6-dichloro-3-nitrobenzenesulfonamide (540 mg, 1.55 mmol), 80% NaH (217 mg,7.25 mmol) and water (0.045mL, 2.46 mmol) were reacted to form the desired product (170 mg, 33%). EI-MS m/z 328(M-H)−.
Reaction SMILES: [F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[CH:5][C:6]2[N:12]=[C:11]([NH:13][NH2:14])[CH2:10][N:9]=[C:8]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:7]=2[CH:21]=1.[Cl:24][CH2:25][C:26](=O)[CH2:27][CH2:28][Cl:29]>O1CCCC1>[F:23][C:2]([F:1])([F:22])[C:3]1[CH:4]=[CH:5][C:6]2[N:12]=[C:11]([NH:13][N:14]=[C:26]([CH2:27][CH2:28][Cl:29])[CH2:25][Cl:24])[CH2:10][N:9]=[C:8]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:7]=2[CH:21]=1
Reactant: O=C(CCl)CCCl
Reactant: NNC1=Nc2ccc(C(F)(F)F)cc2C(c2ccccc2)=NC1
Solvent: C1CCOC1
Product: FC(F)(F)c1ccc2c(c1)C(c1ccccc1)=NCC(NN=C(CCl)CCCl)=N2

Procedure:
In the manner given in Example 1, 7-(trifluoromethyl)-2-hydrazino-5-phenyl-3H-1,4-benzodiazepine in tetrahydrofuran can be treated with 1,4-dichloro-2-butanone under nitrogen to give 7-(trifluoromethyl)-2-[[2-chloro-1-(2-chloroethyl)ethylidene]hydrazino]-5-phenyl-3H-1,4-benzodiazepine.
Reaction SMILES: [O:1]1[CH:3]([CH2:4][O:5][C:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=[CH:8][CH:7]=2)[CH2:2]1.[C:16]([C:18]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)#[N:17]>C(O)C>[C:16]([C:18]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:19][CH2:20][N:21]([CH2:2][CH:3]([OH:1])[CH2:4][O:5][C:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=[CH:8][CH:7]=2)[CH2:22][CH2:23]1)#[N:17]
Reactant: c1ccc2c(OCC3CO3)cccc2c1
Reactant: N#CC1(c2ccccc2)CCNCC1
Solvent: CCO
Product: N#CC1(c2ccccc2)CCN(CC(O)COc2cccc3ccccc23)CC1

Procedure:
A solution of 5.0 parts of 1,2-epoxy-3-(1-naphthoxy)-propane and 5.0 parts of 4-cyano-4-phenylpiperidine in 79 parts of ethanol is refluxed for 24 hours. Evaporation of the solvent from the reaction mixture under reduced pressure affords 3-(4-cyano-4-phenylpiperidino)-1-(1-naphthoxy)-2-propanol. The hydrochloride salt is then prepared by addition of a solution of hydrochloric acid in isopropanol to an isopropanol solution of the free amine. The resulting salt is separated by filtration and recrystallized from isopropanol to afford 3-(4-cyano-4-phenylpiperidino)-1-(1-naphthoxy)-2-propanol hydrochloride, melting at 213°-215° C. and represented by the following structural formula ##STR7##
Reaction SMILES: [CH:1]1([OH:13])C[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1(=O)CCCCCCCCCCC1.C1CCCCCCCCCCC1>>[CH:1](=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11]
Reactant: OC1CCCCCCCCCCC1
Agent: C1CCCCCCCCCCC1
Agent: O=C1CCCCCCCCCCC1
Product: CCCCCCCCCCC=O

Procedure:
Also, in the method of preparing a mixture of cyclododecanol with cyclododecanone by oxidizing cyclododecane with a molecular oxygen-containing gas, undecylaldehyde is produced as a by-product and is contained in refined cyclododecanone fraction obtained by distillation of the mixture.
Reaction SMILES: [N+:1]([O-:4])([OH:3])=[O:2].[CH:5]([CH:7]=[O:8])=[O:6]>>[C:7]([OH:2])(=[O:8])[CH:5]=[O:6].[N+:1]([O-:4])([OH:3])=[O:2]
Reactant: O=CC=O
Solvent: O=[N+]([O-])O
Product: O=CC(=O)O

Procedure:
If nitric acid is added sequentially to an aqueous solution of glyoxal so that the nonoxidizing strong acid is kept at a concentration of 6 wt. % or higher in the reaction mixture, the reaction can proceed in a state wherein nitric acid is not present in the reaction solution in a concentration exceeding 1 wt. %, and an aqueous solution of glyoxylic acid having a final residual nitric acid concentration of 0.1 wt. % or below can be easily obtained. Thus, it is possible to omit the step of removing residual nitric acid, which step is conventionally required, and to use the aqueous solution of glyoxylic acid obtained by the process of the invention directly in further synthesis reactions.