Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[CH:5]=O.[NH2:13][C:14]1[CH:29]=[CH:28][CH:27]=[CH:26][C:15]=1[C:16]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=1)=[O:17]>CCO>[Cl:25][C:22]1[CH:23]=[CH:24][C:19]([N:18]2[C:16](=[O:17])[C:15]3[C:14](=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:13]=[C:5]2[C:4]2[CH:7]=[CH:8][C:9]([N+:10]([O-:12])=[O:11])=[C:2]([CH3:1])[CH:3]=2)=[CH:20][CH:21]=1
Reactant: Cc1cc(C=O)ccc1[N+](=O)[O-]
Reactant: Nc1ccccc1C(=O)Nc1ccc(Cl)cc1
Solvent: CCO
Product: Cc1cc(-c2nc3ccccc3c(=O)n2-c2ccc(Cl)cc2)ccc1[N+](=O)[O-]
Yield: 47.9 %

Procedure:
3-methyl-4-nitro-benzaldehyde (0.268 g, 1.60 mmol) and anyhydrous CuCl2 (0.437 g, 3.20 mmol) were added to a solution of 2-amino-N-(4-chlorophenyl)benzamide (0.400 g, 1.60 mmol) in anyhydrous EtOH (15 mL) and heated at reflux temperature for 3.5 hours. After concentration in vacuo and dissolving the residue in EtOAc, the organics were washed with H2O, then brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification by flash chromatography on silica gel, eluting with 10% to 70% EtOAc in heptane, afforded 3-(4-chlorophenyl)-2-(3-methyl-4-nitrophenyl)quinazolin-4(3H)-one (0.300 g, 48%).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][N:3]2[CH:6]=[C:7]([C:9]3[CH:16]=[CH:15][C:12]([CH:13]=[O:14])=[CH:11][CH:10]=3)[N:8]=[C:2]12.[Br:17]Br>C(O)(=O)C>[Br:17][C:6]1[N:3]2[C:2]([S:1][CH:5]=[CH:4]2)=[N:8][C:7]=1[C:9]1[CH:10]=[CH:11][C:12]([CH:13]=[O:14])=[CH:15][CH:16]=1
Reactant: BrBr
Reactant: O=Cc1ccc(-c2cn3ccsc3n2)cc1
Solvent: CC(=O)O
Product: O=Cc1ccc(-c2nc3sccn3c2Br)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
4-Imidazo[2,1-b]thiazol-6-yl-benzaldehyde (3.8 g, 14.9 mM) is dissolved in 30 mL acetic acid. A solution of bromine (1.1 eq) in acetic acid (15 mL) is added to the reaction mixture. The reaction mixture is stirred for 3 h at room temperature. The solid obtained is collected by filtration and re-dissolved in water (100 ml) and the solution neutralized by aqueous ammonia. The solid obtained is collected by filtration and dried.
Reaction SMILES: C([O:8][CH:9]([CH2:18][CH:19]([F:21])[F:20])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH3:17])C1C=CC=CC=1>CO.[Pd]>[F:20][CH:19]([F:21])[CH2:18][CH:9]([OH:8])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH3:17]
Reactant: Cc1ccccc1CC(CC(F)F)OCc1ccccc1
Agent: [Pd]
Solvent: CO
Product: Cc1ccccc1CC(O)CC(F)F
Reaction time: 5 h

Procedure:
To a solution of 1-(2-(benzyloxy)-4,4-difluorobutyl)-2-methylbenzene (10 g, 34.48 mmol) in MeOH (150 ml) was added 10% Pd/C (1.0 g) under nitrogen and stirred at 40 psi for 5 h. The reaction mixture was filtered through Celite and concentrated under reduced pressure to afford crude compound. The title compound was purified by separation method E. (Yield 6.0 g).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=O.[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([S:17]([NH2:20])(=[O:19])=[O:18])=[CH:13][CH:12]=1.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[N:20][S:17]([C:14]1[CH:13]=[CH:12][C:11]([Cl:10])=[CH:16][CH:15]=1)(=[O:19])=[O:18]
Reactant: NS(=O)(=O)c1ccc(Cl)cc1
Reactant: O=Cc1cccc(O)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: O=S(=O)(N=Cc1cccc(O)c1)c1ccc(Cl)cc1

Procedure:
In a similar manner to Example 2, 1.24 g (10 mmol) of 3-hydroxybenzaldehyde, 1.94 g (10 mmol) of 4-chlorobenzenesulfonamide and 20 mg of TsOH in 150 mL of toluene were heated for 12 hours to give 0.29 g (10%) of SULF-9 as a brown powder: IR (Nujol) 3400, 1658, 1556, 1458, 1155, 1025 cm-1 ; 1H NMR (DMSO-d6, TMS ext std) δ8.85 (s,1), 8.73 (s, 1), 7.7-7.2 (m, 8).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12](=[O:17])[CH2:11][CH2:10]2.[NH:18]([C:22]1[CH:27]=[CH:26][C:25]([SH:28])=[CH:24][CH:23]=1)[C:19]([CH3:21])=[O:20]>>[NH:18]([C:22]1[CH:27]=[CH:26][C:25]([S:28][CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][CH:16]=2)[NH:13][C:12](=[O:17])[CH2:11][CH2:10]3)=[CH:24][CH:23]=1)[C:19]([CH3:21])=[O:20]
Reactant: O=C1CCc2cc(OCCCCBr)ccc2N1
Reactant: CC(=O)Nc1ccc(S)cc1
Product: CC(=O)Nc1ccc(SCCCCOc2ccc3c(c2)CCC(=O)N3)cc1

Procedure:
Prepared analogous to Example 1 from 6-(4-bromo-butoxy)-3,4-dihydro-carbostyril and 4-acetamino-thiophenol.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH:4]([CH2:13][C:14]([NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:15])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[N+:23]([O-])([OH:25])=[O:24]>O>[N+:23]([CH:2]([CH2:3][CH:4]([CH2:13][C:14]([NH:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)=[O:15])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH3:1])([O-:25])=[O:24]
Reactant: O=[N+]([O-])O
Reactant: CCCCCCCCC(CCC)CC(=O)Nc1ccccc1
Solvent: O
Product: CCCCCCCCC(CC(=O)Nc1ccccc1)CC(C)[N+](=O)[O-]
Reaction time: 0.5 h
Yield: 2435.1 %

Procedure:
4-Dodecylacetanilide (252 g) was added portionwise over 45 minutes to a stirred solution of nitric acid (density 1.50 g. ml.) (210 ml) and water (23 ml) keeping the temperature between 35° and 40° C. The mixture was stirred for a further 30 minutes, drowned into cold water (1200 ml) and the precipitated solid filtered off, washed acid free with water, dried and recrystallised from ethanol to give 202 g of 2-nitro-4-dodecylacetanilide as fine needles, melting at 71°-2° C.
Reaction SMILES: [F:1][C:2]1[CH:26]=[CH:25][C:5]([O:6][C:7]2[C:12]([CH:13]([CH2:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[OH:14])=[CH:11][CH:10]=[CH:9][N:8]=2)=[CH:4][CH:3]=1.CC(C)=O.OS(O)(=O)=O.O=[Cr](=O)=O>CC(C)=O.CCCCCC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]2[C:12]([C:13](=[O:14])[CH2:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)=[CH:11][CH:10]=[CH:9][N:8]=2)=[CH:25][CH:26]=1
Reactant: COc1ccc(CCC(O)c2cccnc2Oc2ccc(F)cc2)cc1
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: CC(C)=O
Solvent: CCCCCC
Product: COc1ccc(CCC(=O)c2cccnc2Oc2ccc(F)cc2)cc1
Temperature: 25 °C
Yield: 77.1 %

Procedure:
A solution of 353 mg (1.00 mmol) 2-(4-Fluorophenoxy)-a-[2-(4-methoxyphenyl)ethyl]-3-pyridinemethanol in 5 mL of acetone was cooled to 0° C. and treated with 1.6 mL (2.00 mmol) of 1.25 M Jones Reagent solution. The mixture was allowed to warm to rt and then quenched by the addition of 5 mL of isopropanol. The precipitate was removed by filtration, and the filtrate was evaporated and partitioned between 50 mL of saturated aqueous sodium hydrogencarbonate solution and 100 mL of EtOAc. The separated organic layer was combined with a 100 mL EtOAc backwash of the aqueous layer, washed with brine (50 mL), dried (Na2SO4), and evaporated. Trituration of the residue in hexane gave 271 mg (77% yield) of the title compound, mp 73-74° C. 1H NMR (CDCl3) d 3.03 (2H, t, J=7 Hz), 3.43 (2H, t, J=7 Hz), 3.78 (3H, s), 6.75-7.18 (9H, m), 8.17 (1H, dd, J=2.8 Hz), ), 8.25 (1H, dd, J=2.4 Hz); Anal. Calcd for C21H18NO3F.0.25 H2O; C, 70.87; H, 5.10; N, 3.94. Found: C, 70.88; H, 4.79; N, 3.79.
Reaction SMILES: Cl.C(OC([NH:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)=[O:18])=[CH:13][CH:12]=1)=O)(C)(C)C>O1CCOCC1.ClCCl>[CH:19]1([C:17]([C:14]2[CH:15]=[CH:16][C:11]([CH2:10][NH2:9])=[CH:12][CH:13]=2)=[O:18])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]1
Reactant: CC(C)(C)OC(=O)NCc1ccc(C(=O)C2CCCCC2)cc1
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Product: NCc1ccc(C(=O)C2CCCCC2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 92.6 %

Procedure:
Add 4N hydrogen chloride in dioxane (1 mL) to a stirred solution of N-(tert-butoxycarbonyl)-4-cyclohexanecarbonyl-benzylamine (197 mg, 0.621 mmol) in anhydrous dichloromethane (4 mL) and stir the mixture at ambient temperature for 16 h. Concentrate in vacuo and partition the residue between dichloromethane and saturated aqueous NaHCO3. Extract the aqueous phase twice with dichloromethane. Dry the combined organic extracts over Na2SO4, filter and concentrate in vacuo to give the title compound (125 mg, 93%) that was used without any further purification. MS (ES+) m/z: 218 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:8]#[CH:9])[CH:7]=1.[Cl:10][C:11]1[CH:16]=[C:15](I)[CH:14]=[CH:13][C:12]=1[F:18].C(N(CC)CC)C>C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:8]#[C:9][C:15]2[CH:14]=[CH:13][C:12]([F:18])=[C:11]([Cl:10])[CH:16]=2)[CH:7]=1
Reactant: C#Cc1cncc(Cl)c1
Reactant: Fc1ccc(I)cc1Cl
Agent: [Cu]I
Agent: c1ccc([P]([Pd][P](c2ccccc2)(c2ccccc2)c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Product: Fc1ccc(C#Cc2cncc(Cl)c2)cc1Cl
Temperature: 60 °C
Yield: 71 %

Procedure:
Add bis(triphenylphosphine)palladium (II) dichloride (64 mg, 0.091 mmol), copper (I) iodide (35 mg, 0.18 mmol), and 3-chloro-5-ethynylpyridine, (prepared as described in PREPARATION 27), (250 mg, 1.8 mmol) to a solution of 2-chloro-1-fluoro -4-iodobenzene (560 mg, 2.2 mmol) in triethylamine (3.8 mL, 27 mmol) and heat at 60° C. for 5 h. Cool to room temperature and concentrate. Purify by silica gel chromatography, eluting with 50:50 to 100:0 dichloromethane:hexanes, followed by a second silica gel chromatography, eluting with 100:0 to 90:10 hexanes:ethyl acetate, to give the title compound as a white solid (340 mg, 70%).
Reaction SMILES: Cl[C:2]1[N:3]=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)=[CH:6][CH:7]=1.[CH:18]([NH:20][NH2:21])=O>C(O)CCC>[F:15][C:14]([F:17])([F:16])[C:11]1[CH:12]=[CH:13][C:8]([C:5]2[CH:6]=[CH:7][C:2]3[N:3]([CH:18]=[N:20][N:21]=3)[N:4]=2)=[CH:9][CH:10]=1
Reactant: NNC=O
Reactant: FC(F)(F)c1ccc(-c2ccc(Cl)nn2)cc1
Solvent: CCCCO
Product: FC(F)(F)c1ccc(-c2ccc3nncn3n2)cc1

Procedure:
A mixture of 4.50 g. of 3-chloro-6-(α,α,α-trifluoro-p-tolyl)pyridazine, 2.09 g. of formylhydrazine and 100 ml. of n-butanol is stirred and refluxed for 3 days. The solvent is removed and the residue dissolved in methylene chloride, passed through magnesol and the solid from the filtrate recrystallized from methylene chloride/hexane to afford the product as white crystals, m.p. 160°-161° C.
Reaction SMILES: [H-].[Na+].[N+:3]([N:6]=[C:7]1[NH:11][CH2:10][CH2:9][NH:8]1)([O-:5])=[O:4].[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19]Cl)=[CH:15][N+:14]=1[O-:21]>C(#N)C>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:8]2[CH2:9][CH2:10][NH:11][C:7]2=[N:6][N+:3]([O-:5])=[O:4])=[CH:15][N+:14]=1[O-:21]
Reactant: [O-][n+]1cc(CCl)ccc1Cl
Reactant: O=[N+]([O-])N=C1NCCN1
Agent: [H-]
Agent: [Na+]
Solvent: CC#N
Product: O=[N+]([O-])N=C1NCCN1Cc1ccc(Cl)[n+]([O-])c1
Temperature: 0 °C
Reaction time: 1.5 h

Procedure:
0.85 g of a 55% sodium hydride dispersion in mineral oil is added in portions to a solution of 2.7 g of 2-nitroimino-imidazolidine in 70 ml of acetonitrile. The mixture is stirred for 1.5 hours under a nitrogen atmosphere, and then 3.72 g of 2-chloro-5-chloromethyl-pyridine-N-oxide are added in portions. The reaction mixture is stirred at room temperature for 16 hours and then filtered. The crude product is crystallised out by cooling the filtrate to 0° C. The product is separated off and washed with diethyl ether, yielding pure 2-chloro-5-(2-nitroimino-imidazolidin-1-yl-methyl)-pyridine-N-oxide, m.p. 200° C. (with decomposition).
Reaction SMILES: FC(F)(F)C(O)=O.[F:8][C:9]([F:15])([F:14])[S:10]([OH:13])(=[O:12])=[O:11].COC1C=CC(C[S:23][C@@H:24]2[CH2:28][N:27]([C:29]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=3)=[O:30])[C@H:26]([C:42]([N:44]3[CH2:50][CH2:49][CH2:48][N:47]([CH2:51][CH2:52][O:53][C:54](=[O:56])[NH2:55])[CH2:46][CH2:45]3)=[O:43])[CH2:25]2)=CC=1>C1(OC)C=CC=CC=1>[F:8][C:9]([F:15])([F:14])[S:10]([OH:13])(=[O:12])=[O:11].[C:54]([O:53][CH2:52][CH2:51][N:47]1[CH2:48][CH2:49][CH2:50][N:44]([C:42]([C@@H:26]2[CH2:25][C@H:24]([SH:23])[CH2:28][N:27]2[C:29]([O:31][CH2:32][C:33]2[CH:34]=[CH:35][C:36]([N+:39]([O-:41])=[O:40])=[CH:37][CH:38]=2)=[O:30])=[O:43])[CH2:45][CH2:46]1)(=[O:56])[NH2:55]
Reactant: COc1ccc(CS[C@H]2C[C@@H](C(=O)N3CCCN(CCOC(N)=O)CC3)N(C(=O)OCc3ccc([N+](=O)[O-])cc3)C2)cc1
Agent: O=S(=O)(O)C(F)(F)F
Solvent: O=C(O)C(F)(F)F
Solvent: COc1ccccc1
Product: NC(=O)OCCN1CCCN(C(=O)[C@@H]2C[C@H](S)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)CC1
Reaction time: 1 h

Procedure:
2.7 ml of trifluoroacetic acid and 88 μl of trifluoromethanesulfonic acid were added, whilst ice-cooling, to a solution of 308 mg of (2S,4S)-4-(4-methoxybenzylthio)-2-[4-(2-carbamoyloxyethyl) -1-homopiperazinylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine dissolved in 543 μl of anisole, and the resulting mixture was stirred a the same temperature for 1 hour. At the end of this time, the reaction mixture was worked up in a similar manner to that described in Example 32(1), to afford 315 mg of the title compound.
Reaction SMILES: [N:1]([C:4]1[S:8][C:7]2[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:6]=2[C:5]=1[C:15]([O:17]C)=O)=[C:2]=[S:3].[N:19]1([CH2:24][CH2:25][CH2:26][NH2:27])[CH:23]=[CH:22][N:21]=[CH:20]1>>[N:19]1([CH2:24][CH2:25][CH2:26][N:27]2[C:15](=[O:17])[C:5]3[C:6]4[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][C:7]=4[S:8][C:4]=3[NH:1][C:2]2=[S:3])[CH:23]=[CH:22][N:21]=[CH:20]1
Reactant: NCCCn1ccnc1
Reactant: COC(=O)c1c(N=C=S)sc2c1CCCCCC2
Product: O=c1c2c3c(sc2[nH]c(=S)n1CCCn1ccnc1)CCCCCC3

Procedure:
The compound was synthesized starting from methyl 4,5,6,7,8,9-hexahydro-2-isothiocyanatocycloocta[b]thiophene-3-carboxylate (0.004 g, 0.01 mmol) and 3-(1H-imidazol-1-yl)propan-1-amine (0.002 g, 0.01 mmol) as described above.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([C:17]3[CH:22]=[C:21]([O:23][CH2:24][CH2:25][CH2:26][OH:27])[CH:20]=[CH:19][C:18]=3[CH3:28])=[O:16])=[C:11]([N+:29]([O-])=O)[CH:10]=2)=[C:4]([CH3:32])[CH:3]=1>CO.[Pd]>[NH2:29][C:11]1[CH:10]=[C:9]([NH:8][C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=2[CH3:32])[CH:14]=[CH:13][C:12]=1[C:15]([C:17]1[CH:22]=[C:21]([O:23][CH2:24][CH2:25][CH2:26][OH:27])[CH:20]=[CH:19][C:18]=1[CH3:28])=[O:16]
Reactant: Cc1cc(F)ccc1Nc1ccc(C(=O)c2cc(OCCCO)ccc2C)c([N+](=O)[O-])c1
Agent: [Pd]
Solvent: CO
Product: Cc1cc(F)ccc1Nc1ccc(C(=O)c2cc(OCCCO)ccc2C)c(N)c1
Reaction time: 1 h

Procedure:
Compound 299 (0.026 g, 0.059 mmol) was dissolved in MeOH (2 mL). A catalytic amount of palladium on charcoal was added and the mixture was stirred under a hydrogen atmosphere for 1 h. The suspension was filtered and the filtrate was concentrated in vacuo. The crude product was purified by flash chromatography using EtOAc/petroleum ether (40-60) 1:1→3:1 as the eluent. This afforded the title compound. 1H NMR (CDCl3) δ 7.18 (dd, 1H), 7.11 (d, 1H), 7.03 (d, 1H), 7.00-6.80 (m, 3H), 6.76 (d, 1H), 6.45 (bs, 2H), 5.89 (dd, 1H), 5.75 (d, 1H), 5.59 (s, 1H), 4.08 (t, 2H), 3.83 (t, 2H), 2.22 (s, 3H), 2.18 (s, 3H), 2.01 (m, 2H)
Reaction SMILES: [S:1]1[CH2:7][C:5](=[O:6])[NH:4][C:2]1=[S:3].[CH3:8][O:9][C:10]1[CH:11]=[C:12]([CH:18]=[CH:19][C:20](=O)[CH2:21][CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:13]=[CH:14][C:15]=1[O:16][CH3:17].C([O-])(=O)C.[NH4+].C1(C)C=CC=CC=1>C(OCC)(=O)C.O>[CH3:8][O:9][C:10]1[CH:11]=[C:12]([CH:18]=[CH:19][C:20](=[C:7]2[S:1][C:2](=[S:3])[NH:4][C:5]2=[O:6])[CH2:21][CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:13]=[CH:14][C:15]=1[O:16][CH3:17]
Reactant: O=C1CSC(=S)N1
Reactant: CCOC(=O)CCCC(=O)C=Cc1ccc(OC)c(OC)c1
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Solvent: O
Product: CCOC(=O)CCCC(C=Cc1ccc(OC)c(OC)c1)=C1SC(=S)NC1=O
Yield: 11.9 %

Procedure:
A mixture of 1.60 g (0.012 mol) of rhodanine, 3.06 g (0.01 mol) of ethyl 7-(3,4-dimethoxyphenyl)-5-oxo-6-heptenoate, 0.77 g (0.01 mol) of ammonium acetate and 20 ml of toluene was heated under reflux for 8 hours. After cooling, 100 ml of water were added to the reaction mixture d with ethyl acetate (3×100 ml). The ethyl acetate layer was washed three times with water and once with a saturated saline solution, dried over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure to afford a reddish brown oily substance. The oily substance was purified by silica gel column chromatography (eluent, chloroform) to obtain 0.5 g of ethyl 7-(3,4-dimethoxyphenyl)-5-(4-oxo-2-thioxo-5-thiazolidinylidene)-6-heptenoate. To 0.21 g of this compound was added 5 ml of water and 1 ml of 5% sodium hydroxide solution and the mixture was stirred at room temperature for 3 hours. This mixture was acidified with 10% hydrochloric acid, 100 ml of water was added to the acidified mixture which was extracted with ethyl acetate (3 ×120 ml). The ethyl acetate layer was washed three times with water and once with saturated saline solution, dried over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent, chloroform : methanol ™10:1) to obtain 0.12 g of Isomer A of 7-(3,4-dimethoxyphenyl)-5-(4-oxo-2-thioxo-5-thiazolidinylidene)-6-heptenoic acid from the first eluate and 0.03 g of Isomer B from the subsequent eluate.
Reaction SMILES: [NH:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[C:4](=[O:11])OC1=O.[CH:13]([C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1)([CH3:15])[CH3:14]>CN(C=O)C>[NH2:1][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=1[C:4]([NH:20][C:19]1[CH:21]=[CH:22][C:16]([CH:13]([CH3:15])[CH3:14])=[CH:17][CH:18]=1)=[O:11]
Reactant: O=c1[nH]c2ccccc2c(=O)o1
Reactant: CC(C)c1ccc(N)cc1
Solvent: CN(C)C=O
Product: CC(C)c1ccc(NC(=O)c2ccccc2N)cc1

Procedure:
A solution of 1H-benzo[d][1,3]oxazine-2,4-dione (2.0 g, 12.2 mmol) and 4-isopropylaniline (1.92 mL, 13.5 mmol) in anhydrous DMF (10 mL) was stirred at 115° C. for 6 hours under nitrogen. DMF was removed and the residue was mixed with water (100 mL) and dichloromethane (150 mL). The organic phase was separated and washed with brine (50 mL). The solvent was removed and the residue was washed with ether (50 mL) to give 2-amino-N-(4-isopropyl-phenyl)-benzamide as a solid. Yield: 0.80 g (25.8%).
Reaction SMILES: [C:1]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[CH:6][CH:5]=1)(=O)[CH3:2].Cl.[NH2:15][OH:16]>N1C=CC=CC=1>[C:1](=[N:15][OH:16])([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[CH:6][CH:5]=1)[CH3:2]
Reactant: CC(=O)c1cccc2ccccc12
Reactant: NO
Agent: Cl
Solvent: c1ccncc1
Product: CC(=NO)c1cccc2ccccc12
Temperature: 25 °C
Reaction time: 120 h
Yield: 65 %

Procedure:
In a 50 ml round-bottom flask, a mixture of acetonaphthone, hydroxylamine hydrochloride in pyridine was stirred, at room temperature under nitrogen blanket, for five days. The reaction mixture was then concentrated under vacuum to remove most of pyridine. The oil was then dissolved in dichloromethane. The product precipitated on standing. The product was obtained as a white solid in 65% yield.
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([C:17]([OH:20])([CH3:19])[CH3:18])[N:8]2[CH:11]([CH3:16])[C:12](OC)=[O:13])=[C:4]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[N:3]=1.[AlH4-].[Li+].[NH4+].[Cl-].[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1COCC1.C(Cl)Cl>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([C:17]([OH:20])([CH3:19])[CH3:18])[N:8]2[CH:11]([CH3:16])[CH:12]=[O:13])=[C:4]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[N:3]=1
Reactant: COC(=O)C(C)n1c(C(C)(C)O)nc2c(N3CCOCC3)nc(Cl)nc21
Agent: O=C([O-])[C@H](O)[C@@H](O)C(=O)[O-]
Agent: [AlH4-]
Agent: [Cl-]
Solvent: C1CCOC1
Solvent: ClCCl
Product: CC(C=O)n1c(C(C)(C)O)nc2c(N3CCOCC3)nc(Cl)nc21
Temperature: -78 °C
Reaction time: 1 h
Yield: 62 %

Procedure:
Methyl 2-(2-chloro-8-(2-hydroxypropan-2-yl)-6-morpholino-9H-purin-9-yl)propanoate (1.6 g, 4.1 mmol) was dissolved in THF (30 mL) and cooled to −78° C. The reaction mixture was treated with a 1.0M solution of lithium tetrahydroaluminate in THF (8.6 mL) and stirred at −78° C. for 1 hr. A saturated solution of NH4Cl was added and the mixture was diluted with DCM. The reaction mixture was treated with a saturated solution of Rochelle's salt and stirred on high at ambient temperature for 1 hr. The layers were separated and the aqueous phase was extracted into DCM/MeOH (3×), dried over sodium sulfate, filtered, and absorbed onto celite for purification by flash chromatography to afford 2-(2-chloro-8-(2-hydroxypropan-2-yl)-6-morpholino-9H-purin-9-yl)propanal as a white foam (900 mg, 62%). LC/MS (ESI+): m/z 384 (M+H)
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]([C:10]([C@@H:12]2[CH2:16][CH2:15][CH2:14][N:13]2[CH:17]([CH3:19])[CH3:18])=O)N)=[N:6][CH:7]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC[N:41](CC)CC.ClC(Cl)(Cl)C(Cl)(Cl)Cl>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:8]([C:10]([C@@H:12]3[CH2:16][CH2:15][CH2:14][N:13]3[CH:17]([CH3:19])[CH3:18])=[N:41][N:6]=2)[CH:7]=1
Reactant: CC(C)N1CCC[C@H]1C(=O)N(N)c1ccc(F)cn1
Reactant: CCN(CC)CC
Agent: ClC(Cl)(Cl)C(Cl)(Cl)Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)N1CCC[C@H]1c1nnc2ccc(F)cn12
Temperature: 25 °C
Reaction time: 8 h
Yield: 68.2 %

Procedure:
To a solution of Intermediate 58a (346 mg, 1.30 mmol), Ph3P (681 mg, 2.60 mmol) and Et3N (723 μL, 5.20 mmol) in THF (10.0 mL) at 0° C. was added hexachloroethane (616 mg, 2.60 mmol). The reaction was stirred at RT overnight then partitioned between EtOAc and water. The aqueous layer was then extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was dissolved in MeOH and loaded onto an SCX-2 cartridge, which was washed with MeOH. The product was eluted with 2M NH3 in MeOH; concentration in vacuo gave the title compound (220 mg, 68%). LCMS (Method 4): Rt 0.32 min, m/z 249.1 [MH+].
Reaction SMILES: O[CH2:2][C:3]1([C:18]2[C:27]([OH:28])=[CH:26][C:21]3[N:22]=[C:23]([CH3:25])[S:24][C:20]=3[CH:19]=2)[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[C:4]1=[O:17].ClC1C=CC(Cl)=C2C=1C(C1C(O)=CC3OCOC=3C=1)(CO)C(=O)N2CCCCC>>[CH3:25][C:23]1[S:24][C:20]2[CH:19]=[C:18]3[C:3]4([CH2:2][O:28][C:27]3=[CH:26][C:21]=2[N:22]=1)[C:11]1[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=1)[N:5]([CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[C:4]4=[O:17]
Reactant: CCCCCN1C(=O)C(CO)(c2cc3sc(C)nc3cc2O)c2ccccc21
Agent: CCCCCN1C(=O)C(CO)(c2cc3c(cc2O)OCO3)c2c(Cl)ccc(Cl)c21
Product: CCCCCN1C(=O)C2(COc3cc4nc(C)sc4cc32)c2ccccc21

Procedure:
Following the procedure as described in EXAMPLE 1.22, and making non-critical variations using 3-(hydroxymethyl)-3-(5-hydroxy-2-methyl-1,3-benzothiazol-6-yl)-1-pentyl-1,3-dihydro-2H-indol-2-one to replace 4,7-dichloro-3-(6-hydroxy-1,3-benzodioxol-5-yl)-3-(hydroxymethyl)-1-pentyl-1,3-dihydro-2H-indol-2-one, the title compound was obtained (50%) as a white solid: mp 105-107° C.; 1H NMR (300 MHz, CDCl3) δ 7.59 (d, 1H), 7.28 (dt, 1H), 7.02-6.92 (m, 2H), 5.02 (d, 1H), 4.77 (d, 1H), 4.01 (m, 1H), 3.64 (m, 1H), 2.54 (s, 3H), 1.92-1.71 (m, 2H), 1.54-1.34 (m, 4H), 0.92 (t, 3H); 13C NMR (75 MHz, CDCl3) δ 176.7, 169.2, 160.2, 149.2, 142.7, 138.3, 132.7, 129.0, 128.6, 123.5, 122.7, 122.1, 120.2, 108.6, 108.3, 80.1, 58.1, 40.7, 29.1, 27.0, 22.5, 20.2, 14.1; MS (ES+) m/z 379.5 (M+1).
Reaction SMILES: [CH:1]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([C:16](=[NH:20])[O:17][CH2:18][CH3:19])[CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[S:21]1[CH:25]=[CH:24][CH:23]=[C:22]1[C:26](Cl)=[O:27]>>[S:21]1[CH:25]=[CH:24][CH:23]=[C:22]1[C:26]([N:20]=[C:16]([N:7]1[CH2:6][C:5]2[CH:4]=[CH:3][CH:2]=[CH:1][C:11]=2[C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[CH2:8]1)[O:17][CH2:18][CH3:19])=[O:27]
Reactant: CCOC(=N)N1Cc2ccccc2-c2ccccc2C1
Reactant: O=C(Cl)c1cccs1
Product: CCOC(=NC(=O)c1cccs1)N1Cc2ccccc2-c2ccccc2C1

Procedure:
starting from ethyl 5,7-dihydro-6H-dibenz[c,e]azepine-6-carboximidate and 2-thienylcarbonyl chloride, there is obtained ethyl N-(2-thienylcarbonyl)-5,7-dihydro-6H-dibenz[c,e]azepine-6-carboximidate as a solid, mass spectrum m/e:M+ 376 (10), 347 (13), 194 (100), 111 (48); starting from ethyl 5,7-dihydro-6H-dibenz[c,e]azepine-6-carboximidate and 1-naphthoyl chloride, there is obtained ethyl N-(1-naphthylcarbonyl)-5,7-dihydro-6H-dibenz[c,e]azepine-6-carboximidate as a foam, mass spectrum m/e: M+ 420 (8), 391 (6), 194 (100), 155 (32), 27 (28);