Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:22])[C:12]3[CH:19]=[C:18]([CH2:20]O)[S:17][C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:4][CH:3]=1.N1C(C)=CC(C)=CC=1C.CS(Cl)(=O)=O.[CH3:39][NH:40][CH2:41][CH:42]([OH:50])[C:43]1[CH:44]=[CH:45][C:46]([OH:49])=[CH:47][CH:48]=1>CN(C=O)C.CN(C1C=CN=CC=1)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:22])[C:12]3[CH:19]=[C:18]([CH2:20][N:40]([CH2:41][CH:42]([OH:50])[C:43]4[CH:48]=[CH:47][C:46]([OH:49])=[CH:45][CH:44]=4)[CH3:39])[S:17][C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:23][CH:24]=1
Reactant: Cn1cc(C(=O)NCc2ccc(Cl)cc2)c(=O)c2cc(CO)sc21
Reactant: CNCC(O)c1ccc(O)cc1
Agent: CN(C)c1ccncc1
Agent: CS(=O)(=O)Cl
Solvent: CN(C)C=O
Solvent: O
Solvent: Cc1cc(C)nc(C)c1
Product: CN(Cc1cc2c(=O)c(C(=O)NCc3ccc(Cl)cc3)cn(C)c2s1)CC(O)c1ccc(O)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 59.8 %

Procedure:
To a solution of N-(4-chlorobenzyl)-2-(hydroxymethyl)-7-methyl-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamide (0.300 g) from Example No. 35 in DMF (17 mL) are added DMAP (16 mg), 2,4,6-collidine (0.27 mL), and methanesulfonyl chloride (0.16 mL). The reaction mixture is stirred at room temperature for 1 h and then synephrine (1.39 g) is added. The mixture is stirred at room temperature for 18 h and is then poured into water (50 mL). The resulting off-white solid is filtered off. Additional material precipitates out of the filtrate. The two lots of material are combined and purified by column chromatography (CH2Cl2, CH2Cl2/methanol, 99/1; 98/2; 96/4) to yield 0.253 g (60%) of the title compound as a white solid.
Reaction SMILES: Cl.C(N(C1C=CC=CC=1)S(C1C=NC(N2C(=O)C(CC3C=NC=CC=3)=C(C)N2)=CC=1)(=O)=O)C.[CH3:34][O:35][CH2:36][C:37]1[CH:38]=[C:39]([CH2:43]O)[CH:40]=[CH:41][CH:42]=1.P(Br)(Br)[Br:46].CO>CCOCC>[Br:46][CH2:43][C:39]1[CH:40]=[CH:41][CH:42]=[C:37]([CH2:36][O:35][CH3:34])[CH:38]=1
Reactant: COCc1cccc(CO)c1
Reactant: BrP(Br)Br
Agent: CCN(c1ccccc1)S(=O)(=O)c1ccc(-n2[nH]c(C)c(Cc3cccnc3)c2=O)nc1
Agent: Cl
Solvent: CO
Solvent: CCOCC
Product: COCc1cccc(CBr)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 39 %

Procedure:
To a solution of 5.91 g (38.8 mmol) of 2 [3-(methoxymethyl)phenyl]methanol in 75 mL of Et2O are added dropwise, at 0° C., 9.1 mL (97.1 mmol) of phosphorus tribromide. The reaction mixture is allowed to warm slowly to room temperature and stirring is continued for 4 hours. The crude reaction mixture is then poured cautiously into a mixture of 100 g of ice and 100 mL of MeOH. After evaporating off the MeOH under reduced pressure, the aqueous phase is extracted with DCM (2×200 mL). The organic phases are combined, dried over Na2SO4, filtered and then concentrated under reduced pressure. The residue obtained is purified by chromatography on a column of silica gel, eluting with a cyclohexane/EtOAc gradient of 0 to 20% EtOAc. 3.25 g of 1-(bromomethyl)-3-(methoxymethyl)benzene are thus obtained in the form of an oil.
Reaction SMILES: [F:1][C:2]([F:36])([F:35])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH2:23][N:24]4C(=O)C5C(=CC=CC=5)C4=O)=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.CO.O.NN>ClCCl>[F:36][C:2]([F:1])([F:35])[O:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH2:23][NH2:24])=[CH:17][CH:16]=3)=[N:11]2)=[CH:8][CH:9]=1
Reactant: O=C1c2ccccc2C(=O)N1CCCc1ccc(-c2ncn(-c3ccc(OC(F)(F)F)cc3)n2)cc1
Agent: NN
Solvent: O
Solvent: CO
Solvent: ClCCl
Product: NCCCc1ccc(-c2ncn(-c3ccc(OC(F)(F)F)cc3)n2)cc1
Temperature: 50 °C
Yield: 95.4 %

Procedure:
To 2-(3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propyl)isoindoline-1,3-dione (C59) (0.373 g, 0.758 mmol) in a 25 mL vial equipped with a stir bar, Vigreux column, and nitrogen was added methanol (7.58 mL) followed by hydrazine monohydrate (0.110 mL, 2.27 mmol). The reaction was heated to 50° C. until determined to be complete by LCMS. The reaction mixture was cooled to room temperature and diluted with dichloromethane. The layers were separated and the aqueous layer was extracted with dichloromethane (2×). The organic layers were washed with sodium hydroxide (1 N, 4×), poured through a phase separator and concentrated. The resultant solid was dried in vacuo over 72 hours at 50° C. to provide the title compound as an off-white solid (0.262 g, 95%): 1H NMR (400 MHz, DMSO-d6) δ 9.38 (s, 1H), 8.10-8.04 (m, 2H), 8.04-7.98 (m, 2H), 7.66-7.59 (m, 2H), 7.35 (d, J=8.1 Hz, 2H), 2.69-2.63 (m, 2H), 2.56 (t, J=6.9 Hz, 2H), 1.74-1.59 (m, 2H), (NH2 not observed); 19F NMR (376 MHz, DMSO-d6) δ −56.96; ESIMS m/z 363 ([M+H]+).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[OH:12])[C:5]([NH:7][NH2:8])=[O:6].Br[CH2:14][CH2:15][O:16][C:17]1[CH:24]=[CH:23][C:20]([CH:21]=O)=[C:19]([O:25][CH3:26])[CH:18]=1.C(OCC)(OCC)OCC.[CH2:37]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH2:40][CH2:39][NH:38]1.[I-].[K+]>CN(C=O)C>[CH2:37]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH2:40][CH2:39][N:38]1[CH2:14][CH2:15][O:16][C:17]1[CH:24]=[CH:23][C:20]([CH:21]=[N:8][NH:7][C:5](=[O:6])[C:4]2[CH:9]=[CH:10][C:11]([OH:12])=[C:2]([Cl:1])[CH:3]=2)=[C:19]([O:25][CH3:26])[CH:18]=1
Reactant: c1ccc2c(c1)CCNC2
Reactant: NNC(=O)c1ccc(O)c(Cl)c1
Reactant: COc1cc(OCCBr)ccc1C=O
Agent: [I-]
Agent: [K+]
Solvent: CCOC(OCC)OCC
Solvent: CN(C)C=O
Product: COc1cc(OCCN2CCc3ccccc3C2)ccc1C=NNC(=O)c1ccc(O)c(Cl)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
The resin bound 3-chloro-4-hydroxybenzoic acid hydrazide (resin—[building block 1]) (3 g, ˜3 mmoles) was swelled in DMF (35 mL) for 30 minutes. Then 4-(2-bromoethoxy)-2-methoxybenzaldehyde (2.33 g, 9 mmoles) and triethyl orthoformate (18 mL) were added and the mixture was shaken at room temperature for 16 hours. The resin was repeatedly swelled in DMF (35 ml, 4 times), CH2Cl2 (35 mL, 6 times) and N-methyl-2-pyrrolidinone (NMP) (35 mL, 2 times) and filtered. The resin was swelled in NMP (40 mL) and 1,2,3,4-tetrahydroisoquinoline (3.75 mL, 30 mmoles) and potassium iodide (1.0 g, 6 mmoles) were added. The resin was shaken at room temperature for 16 hours and filtered. The resin was repeatedly swelled in DMF (40 ml, 5 times), CH2Cl2 (40 mL, 10 times) and filtered. The compound was cleaved off the resin by shaking for 1 hour at room temperature with a 50% solution of trifluoroacetic acid in CH2Cl2 (40 mL). The mixture was filtered and the resin was extracted with CH2Cl2 (40 mL, 2 times). The combined CH2Cl2 extracts were concentrated in vacuo. The residue was dissolved in CH2Cl2 (40 mL) and concentrated in vacuo. The residue was dissolved in methanol (40 mL) and concentrated in vacuo. The residue was partitioned between ethyl acetate (50 mL) and saturated sodium hydrogencarbonate (50 mL). The aqueous phase was extracted with ethyl acetate (50 mL), and the combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified by coloumn chromatography over silica gel (200 mL) eluting with a mixture of CH2Cl2 and methanol (9:1). This afforded 280 mg of the title compound.
Reaction SMILES: [CH2:1]([C@@H:8]1[CH2:14][C@@H:13]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:12](=[O:22])[O:11][C:9]1=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:23]([OH:25])[CH3:24].C1(C)C=CC=CC=1>>[CH2:23]([O:25][C:12]([C@H:13]([CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[CH2:14][C@@H:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:9]([OH:11])=[O:10])=[O:22])[CH3:24]
Reactant: CCO
Reactant: O=C1OC(=O)[C@H](Cc2ccccc2)C[C@H]1Cc1ccccc1
Solvent: Cc1ccccc1
Product: CCOC(=O)[C@H](Cc1ccccc1)C[C@@H](Cc1ccccc1)C(=O)O

Procedure:
The starting material is prepared as follows: 4.0 g of (S,S)-2,4-dibenzylglutaric anhydride is refluxed in 40 ml of ethanol:toluene (3:2) overnight. The reaction mixture is concentrated to yield 4-ethoxycarbonyl-(S,S)-2,4-dibenzylbutyric acid as an oil. Oxalyl chloride (3.5 ml) is added to the solution of 4.5 g of 4-ethoxycarbonyl-(S,S)-2,4-dibenzylbutyric acid in 10 ml of methylene chloride. The mixture is stirred at room temperature overnight and evaporated to yield 4-ethoxycarbonyl-(S,S)-2,4-dibenzylbutyryl chloride, which is used as such without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH:13]([C:20]3[N:21]([CH3:25])[CH:22]=[CH:23][N:24]=3)[NH:14][C:15](=O)[CH2:16][O:17][CH3:18])[CH2:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].Cl.O>O1CCCC1.CCOCC>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH:13]([C:20]3[N:21]([CH3:25])[CH:22]=[CH:23][N:24]=3)[NH:14][CH2:15][CH2:16][O:17][CH3:18])[CH2:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: COCC(=O)NC(c1nccn1C)C1(c2ccc(Cl)c(Cl)c2)CCC1
Agent: Cl
Solvent: O
Solvent: C1CCOC1
Solvent: CCOCC
Product: COCCNC(c1nccn1C)C1(c2ccc(Cl)c(Cl)c2)CCC1
Temperature: 0 °C
Reaction time: 48 h
Yield: 41703.7 %

Procedure:
Borane-methyl sulphide complex (5 ml) was added dropwise to a solution of the acetamide (3.3 g) prepared as above in tetrahydrofuran (100 ml) and the mixture stirred for 2 days. Ice-water was added cautiously and the resulting mixture basified. The basified mixture was extracted with ether and the extracts washed and dried. Removal of the ether gave a residue which was dissolved in ether. Hydrogen chloride gas was passed through the solution to give a hydrochloride of N-{[1-(3,4-dichlorophenyl)cyclobutyl][1-methylimidazol-2-yl]methyl}-2-methoxyethylamine containing 1.8 moles of hydrochloride and 1.6 moles of water which decomposed when heated to 150° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[CH3:20][O:21][CH2:22][CH2:23]Br>>[CH3:20][O:21][CH2:22][CH2:23][O:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]
Reactant: COC(=O)c1cc(O)cc(OCc2ccccc2)c1
Reactant: COCCBr
Product: COCCOc1cc(OCc2ccccc2)cc(C(=O)OC)c1

Procedure:
The subtitle compound was prepared from the product of step (i) (2.31 g) and 2-bromoethyl methyl ether 90.92 ml) by the method of example 11 step (i). Yield 2.74 g.
Reaction SMILES: CS(Cl)(=O)=[O:3].[Cl:6][C:7]1[CH:30]=[CH:29][C:10]([CH2:11][NH:12][C:13]([C:15]2[C:24](=[O:25])[C:23]3[C:18](=[CH:19][CH:20]=[C:21](CO)[CH:22]=3)[N:17]([CH3:28])[CH:16]=2)=[O:14])=[CH:9][CH:8]=1.[N:31]1[C:36]([CH3:37])=[CH:35][C:34]([CH3:38])=C[C:32]=1C>CN(C1C=CN=CC=1)C.CN(C=O)C>[Cl:6][C:7]1[CH:30]=[CH:29][C:10]([CH2:11][NH:12][C:13]([C:15]2[C:24](=[O:25])[C:23]3[C:18](=[CH:19][CH:20]=[C:21]([CH2:32][N:31]4[CH2:38][CH:34]5[CH2:35][CH:36]4[CH2:37][O:3]5)[CH:22]=3)[N:17]([CH3:28])[CH:16]=2)=[O:14])=[CH:9][CH:8]=1
Reactant: CS(=O)(=O)Cl
Reactant: Cn1cc(C(=O)NCc2ccc(Cl)cc2)c(=O)c2cc(CO)ccc21
Reactant: Cc1cc(C)nc(C)c1
Agent: CN(C)c1ccncc1
Solvent: CN(C)C=O
Product: Cn1cc(C(=O)NCc2ccc(Cl)cc2)c(=O)c2cc(CN3CC4CC3CO4)ccc21
Temperature: 25 °C
Yield: 53 %

Procedure:
Methanesulfonyl chloride (0.06 mL) is added to a cold (0° C.) solution of N-(4-chlorobenzyl)-6-(hydroxymethyl)-1-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxamide (250 mg) from Preparation No. 10, DMAP (14.4 mg), and 2,4,6-collidine (0.11 mL) in anhydrous DMF (12 mL). The mixture is stirred at room temperature until the starting material is consumed. (1S, 4S)-(+)-2-Aza-5-oxabicyclo[2.2.1]heptane hydrochloride (475.9 mg) and Et3N (0.49 mL) are added to the solution. The reaction mixture is heated to 65° C. overnight. The mixture is cooled to room temperature and filtered to remove the salt that had precipitated out of solution. The filtrate is diluted with water (125 mL) to precipitate the product. The solid is adsorbed onto silica and purified by column chromatography (eluent 1% MeOH in CH2Cl2 (1 L), 2% MeOH in CH2Cl2 (1 L), 3% MeOH in CH2Cl2 (2.5 L)). Fractions homogenous by TLC are combined, concentrated, and recrystallized from CH2Cl2/hexanes to afford 164.0 mg (53%) of the title compound as a white solid.
Reaction SMILES: CO[C:3](=[O:26])[CH:4]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[NH:5][C:6]([NH:8][C:9]1[S:10][C:11]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:12]=2[N:13]=1)=[S:7].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[F:18][C:16]1[CH:15]=[CH:14][C:12]2[N:13]=[C:9]([N:8]3[C:3](=[O:26])[CH:4]([CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[NH:5][C:6]3=[S:7])[S:10][C:11]=2[CH:17]=1
Reactant: COC(=O)C(Cc1ccccc1)NC(=S)Nc1nc2ccc(F)cc2s1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: O=C1C(Cc2ccccc2)NC(=S)N1c1nc2ccc(F)cc2s1
Temperature: 25 °C
Yield: 30.4 %

Procedure:
A solution of N-[[(6-fluoro-2-benzothiazolyl)amino]thioxomethyl]-DL-phenylalanine methyl ester (0.90 g, 2.31 mmol) and p-toluene sulfonic acid hydrate (0.20 g 1.05 mmol) in toluene (80 mL) was refluxed with a Dean-Stark trap for 48 h. The reaction was cooled to room temperature, solvent removed under reduced pressure, residue taken up in ethyl acetate, washed with saturated sodium bicarbonate and saturated sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting product was recrystallized from ethyl ether-hexanes to provide 251 mg (31%) of the titled product: mp 223°-224° C.; IR (KBr, cm-1) 3173, 1767, 1538, 1453, 1388, 1267; 1H NMR (300 MHZ, DMSO-d6) δ 11.02 (s, 1H), 8.00-8.12 (m, 2H), 7.40-7.50 (m, 1H), 7.20-7.39 (m, 5H), 4.97 (t, 1H), 3.20 (d, 2H); MS (FD) m/e 357(M+); UV (EtOH) 265 nm (ε=15680), 223 nm (ε=19505), 201 nm (ε=23665). Anal. Calcd for C17H12FN3OS2 : C, 57.13; H,3.38; N,11.76. Found: C,56.89; H, 3.43; N, 11.60.
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]([CH2:9][N:10]2[C:14]([CH3:15])=[N:13][C:12]([C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:26]=[CH:25][C:24]([O:27][C:28]([F:31])([F:30])[F:29])=[CH:23][CH:22]=4)[N:17]=3)=[N:11]2)[CH:6]=CC=1)=C.C[N+]1([O-])CC[O:36]CC1.C[C:41]([OH:44])([CH3:43])[CH3:42]>O.O=[Os](=O)(=O)=O>[CH3:15][C:14]1[N:10]([CH2:9][C:5]2[CH:6]=[C:42]([CH:41]([OH:44])[CH2:43][OH:36])[CH:1]=[CH:3][CH:4]=2)[N:11]=[C:12]([C:16]2[O:20][N:19]=[C:18]([C:21]3[CH:26]=[CH:25][C:24]([O:27][C:28]([F:31])([F:30])[F:29])=[CH:23][CH:22]=3)[N:17]=2)[N:13]=1
Reactant: CC(C)(C)O
Reactant: C[N+]1([O-])CCOCC1
Reactant: C=Cc1cccc(Cn2nc(-c3nc(-c4ccc(OC(F)(F)F)cc4)no3)nc2C)c1
Agent: O=[Os](=O)(=O)=O
Solvent: O
Product: Cc1nc(-c2nc(-c3ccc(OC(F)(F)F)cc3)no2)nn1Cc1cccc(C(O)CO)c1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a solution of 5-(5-methyl-1-(3-vinylbenzyl)-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole (Example 84; 110 mg, 0.26 mmol) in t-BuOH (5 mL), were added N-methylmorpholine-N-oxide (152 mg, 1.3 mmol) and OsO4 (10 mg, 0.04 mmol). The reaction mixture was stirred at RT for 24 h, diluted with H2O (20 mL) and extracted with EtOAc (2×10 mL). The combined organic layers were washed with H2O (10 mL) and brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure; the residue was purified by prep-HPLC (10% to 40% MeCN/H2O containing 0.1% trifluoroacetic acid) to give the title compound as a white solid; MS (ES+) C21H18F3N5O4 requires: 461. found: 462 [M+H]+; 1H-NMR (500 MHz, DMSO-d6) δ 8.23 (d, J=8.5 Hz, 2H), 7.61 (d, J=8.5 Hz, 2H), 7.33-7.30 (m, 3H), 7.17 (d, J=7 Hz, 1H), 5.56 (s, 2H), 4.54-4.51 (m, 1H), 3.44-3.40 (m, 4H), 2.57 (s, 3H).
Reaction SMILES: C1C=C(C(O)=[O:8])C(C(OO)=O)=CC=1.[CH3:14][O:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[N:22]=[CH:21][CH:20]=[C:19]2[CH2:26][CH2:27][CH:28]1[CH2:33][CH2:32][N:31]([C:34](=[O:41])[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:30][CH2:29]1.[OH-].[Na+]>CCOCC.CO>[CH3:14][O:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[N+:22]([O-:8])=[CH:21][CH:20]=[C:19]2[CH2:26][CH2:27][CH:28]1[CH2:29][CH2:30][N:31]([C:34](=[O:41])[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH2:32][CH2:33]1
Reactant: O=C(O)c1ccccc1C(=O)OO
Reactant: COc1ccc2nccc(CCC3CCN(C(=O)c4ccccc4)CC3)c2c1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: CO
Product: COc1ccc2c(c1)c(CCC1CCN(C(=O)c3ccccc3)CC1)cc[n+]2[O-]
Temperature: 10 °C
Reaction time: 4 h

Procedure:
269 ml of a 0.09M solution of monoperphthalic acid in ether (prepared according VOGEL--Textbook of Practical Organic Chemistry, 1978, 307) are added rapidly to a solution of 7.9 g of 6-methoxy-4-[2-(1-benzoyl-4-piperidyl)-ethyl]-quinoline in 45 ml of methanol, stirred and cooled to 10° C. After four hours at the ambient temperature, a further 20 ml of the same monoperphthalic acid solution are added, and the stirring is then maintained for 15 hours. The reaction mixture is then made alkaline with 100 ml of a 0.7N aqueous solution of sodium hydroxide. The organic phase, separated, is again washed with 100 ml of a 0.5N solution of sodium hydroxide, dried, then concentrated. The residue obtained, after recrystallization from cyclohexane, gives 5.1 g of 6-methoxy-4-[2-(1-benzoyl-4-piperidyl)-ethyl]quinoline-N-oxide melting at 138° C.
Reaction SMILES: [C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH:3]=[CH:2]1.[C:8]1([CH:15]=C[C:12](O)=[CH:11][CH:10]=1)O.C=C/C=C/C.C=C/C=C\C>C1(C)C=CC=CC=1>[CH3:12][CH:11]1[CH2:10][CH:8]=[CH:15][CH:2]2[C:1]([O:6][C:4](=[O:5])[CH:3]12)=[O:7]
Reactant: Oc1ccc(O)cc1
Reactant: O=C1C=CC(=O)O1
Agent: C=C/C=C/C
Agent: C=C/C=C\C
Solvent: Cc1ccccc1
Product: CC1CC=CC2C(=O)OC(=O)C12
Reaction time: 3 h
Yield: 99 %

Procedure:
Maleic anhydride (68.6 parts) and 70 parts of toluene were fed into an autoclave, and melted at 55° C. Then, 0.162 part of hydroquinone was added. Subsequently, 30.9 parts (corresponding to 1.1 moles of trans-1,3-pentadiene per mole of maleic anhydride) of crude trans-1,3-pentadiene composed of 40% of trans-1,3-pentadiene, 20% of cis-1,3-pentadiene and 40% of pentanes was continuously added over 6 hours at 50° C. The temperature was then elevated to 60° C. and the reaction was carried out for 3 hours. After the reaction, the volatile components were removed by distillation at 90° C. under atmospheric pressure. As the Diels-Alder reaction product, 3-methyltetrahydrophthalic anhydride (melting point 61° C.) was obtained in a yield of 99%.
Reaction SMILES: [NH2:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[CH:8]=[C:9]([NH2:15])[C:10]([NH:13][CH3:14])=[CH:11][CH:12]=2)=[C:4]([CH3:18])[CH:3]=1.O.[C:20](=[O:23])(O)[O-].[Na+].[CH:25](O)=O>>[CH3:18][C:4]1[CH:3]=[C:2]([NH:1][CH:20]=[O:23])[CH:17]=[CH:16][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][C:10]2[N:13]([CH3:25])[CH:14]=[N:15][C:9]=2[CH:8]=1
Reactant: CNc1ccc(Oc2ccc(N)cc2C)cc1N
Reactant: O=CO
Reactant: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: Cc1cc(NC=O)ccc1Oc1ccc2c(c1)ncn2C
Temperature: 25 °C
Yield: 97 %

Procedure:
4-(4-amino-2-methylphenoxy)-N1-methylbenzene-1,2-diamine (1.52 g, 6.25 mmol) was dissolved in formic acid (15 mL) and heated to reflux for 6 hours. After cooling to room temperature, the mixture was diluted water (100 mL) and neutralized with sodium bicarbonate. The mixture was partitioned between water and dichloromethane. The organic layer was washed with aqueous NaHCO3, brine, dried over Na2SO4, filtered and concentrated under reduced pressure to provide the product (1.70 g, 97%).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([Cl:8])[N:5]=[C:4]([O:9][C:10]2[C:15]([CH3:16])=[CH:14][C:13]([CH3:17])=[CH:12][C:11]=2[CH3:18])[N:3]=1.[O:19]1[CH2:23][CH:20]1[CH2:21][OH:22].[OH-].[Na+]>ClCCl>[Cl:8][C:6]1[N:7]=[C:2]([O:22][CH2:21][CH:20]2[O:19][CH2:23]2)[N:3]=[C:4]([O:9][C:10]2[C:15]([CH3:16])=[CH:14][C:13]([CH3:17])=[CH:12][C:11]=2[CH3:18])[N:5]=1
Reactant: Cc1cc(C)c(Oc2nc(Cl)nc(Cl)n2)c(C)c1
Reactant: OCC1CO1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: Cc1cc(C)c(Oc2nc(Cl)nc(OCC3CO3)n2)c(C)c1
Temperature: 25 °C
Reaction time: 0.42 h

Procedure:
To a mechanically stirred solution of 50 g (0.155 mol) 2,4-dichloro-6-(2,4,6-trimethylphenoxy)-1,3,5-triazine in 170 ml dichloromethane, cooled to 0°.varies.10° C., was added 26.38 g (0.356 mol) 2,3-epoxy-1-propanol in one portion. Aqueous sodium hydroxide (50% solution; 14.26 g) was added to the mixture dropwise with stirring over about 25 minutes maintaining the reaction temperature between 0° and 10° C. and preferably around 0°-5° C. After stirring an additional 30 minutes, the reaction mixture was allowed to warm slowly to room temperature. The dichloromethane layer was washed with distilled water until neutral and dried over magnesium sulfate. The reaction product was found by proton nuclear magnetic resonance to be 2-chloro-4-glycidoxy-6-(2,4,6-trimethylphenoxy)-1,3,5-triazine.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]([CH3:10])[C:8]#[N:9].C(O)(C)(C)C.[C:16]([O:20][CH3:21])(=[O:19])[CH:17]=[CH2:18]>O>[C:8]([C:7]([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1)([CH3:10])[CH2:18][CH2:17][C:16]([O:20][CH3:21])=[O:19])#[N:9]
Reactant: C=CC(=O)OC
Reactant: CC(C#N)c1ccccn1
Solvent: O
Solvent: CC(C)(C)O
Product: COC(=O)CCC(C)(C#N)c1ccccn1
Yield: 41.8 %

Procedure:
To a dried flask under nitrogen was added 2-(2-pyridinyl)-propanenitrile (Preparation 43, 6.26 g, 47.4 mmol), t-butanol (30 ml), Triton B (6.66 g, 39.8 mmol) and methyl acrylate (6.12 g, 71.1 mmol). The reaction mixture was heated at reflux for 2.5 h. The solid was removed, and the filtrate concentrated in vacuo to give a yellow oil. Water (30 ml) was added and the product was extracted with diethyl ether. The organic extracts were dried (Na2SO4) and concentrated in vacuo to give a light yellow oil (4.32 g, 42%).
Reaction SMILES: [H-].[Na+].[CH2:3]([O:5][C:6](=[O:30])[CH:7]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]=1[N+:27]([O-:29])=[O:28])[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH3:4].[CH3:31]I.O>CN(C)C=O>[CH2:11]([O:10][C:8](=[O:9])[C:7]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]=1[N+:27]([O-:29])=[O:28])([CH3:31])[C:6]([O:5][CH2:3][CH3:4])=[O:30])[CH3:12]
Reactant: CI
Reactant: CCOC(=O)C(C(=O)OCC)c1cccc(C(=O)c2ccccc2)c1[N+](=O)[O-]
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)C(C)(C(=O)OCC)c1cccc(C(=O)c2ccccc2)c1[N+](=O)[O-]
Reaction time: 0.08 h

Procedure:
A slurry of 0.6 g (0.012 mole) of 50% sodium hydride/oil (washed, petroleum ether) in a 10 ml dimethylformamide was treated dropwise with a solution of 3.6 g (0.009 mole) of 2-(3-benzoyl-2-nitrophenyl)propanedioic acid diethyl ester in 20 ml of dimethylformamide. The mixtue was stirred for 5 min and the 4 ml (9.1 g, 0.065 mole) of methyliodide was added and the solution stirred at ambient temperature overnight. The solution was poured into 500 ml of cold water and let stand overnight. The aqueous layer was decanted and the gummy residue was dissolved in diethylether. The ether solution was washed with water and saturated sodium chloride solution, dried over sodium sulfate and concentrated to give 3.5 g (95%) of a gray solid, m.p. 102°-104° C. (recrystallized from 2-propanol).