Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:5][C:6]([NH:8][CH2:9][C:10]([OH:12])=O)=[O:7])[CH:2]([CH3:4])[CH3:3].CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:28][C:29]1[C:37]2[C:32](=[N:33][CH:34]=[N:35][C:36]=2[NH:38][C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([Cl:45])[CH:40]=2)[NH:31][N:30]=1>C1COCC1.C(O)C>[Cl:45][C:41]1[CH:40]=[C:39]([NH:38][C:36]2[N:35]=[CH:34][N:33]=[C:32]3[NH:31][N:30]=[C:29]([NH:28][C:10](=[O:12])[CH2:9][NH:8][C:6]([O:5][CH2:1][CH:2]([CH3:3])[CH3:4])=[O:7])[C:37]=23)[CH:44]=[CH:43][CH:42]=1
Reactant: CC(C)COC(=O)NCC(=O)O
Reactant: Nc1n[nH]c2ncnc(Nc3cccc(Cl)c3)c12
Agent: CC(C)COC(=O)Cl
Solvent: CN1CCOCC1
Solvent: C1CCOC1
Solvent: CCO
Product: CC(C)COC(=O)NCC(=O)Nc1n[nH]c2ncnc(Nc3cccc(Cl)c3)c12

Procedure:
Analogously to Example 5. 502 mg (2.86 mmol) of N-isobutyloxycarbonyl-glycine in 5.9 ml of THF and 580 μl (5.3 mmol) of NMM are activated with 375 μl (2.86 mmol) of isobutyl chloroformate and then reacted with 745 mg (2.86 mmol) of 3-amino-4-(3-chloro-phenylamino)-1H-pyrazolo[3,4-d]pyrimidine (see Step 1.6). Stirring in 7.5 ml of boiling ethanol and filtering while hot yield 4-(3-chloro-phenylamino)-3-([N-iso-butyloxycarbonyl-glycyl]-amino)-1H-pyrazolo[3,4-d]pyrimidine; HPLC: tRet(grad20-100/20)=12.8; FAB-MS: (M+H)+=418.
Reaction SMILES: [C:1]([O:5][C:6](=[O:21])[CH2:7][C@@H:8]([CH2:12][CH2:13][CH2:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)[C:9]([OH:11])=[O:10])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.[NH2:39]/[C:40](=[N:54]\O)/[C@@H:41]1[CH2:46][CH2:45][CH2:44][CH2:43][N:42]1[C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48]>C(Cl)Cl.O>[NH2:54]/[C:40](=[N:39]\[O:10][C:9](=[O:11])[C@@H:8]([CH2:7][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:21])[CH2:12][CH2:13][CH2:14][CH:15]1[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]1)/[C@@H:41]1[CH2:46][CH2:45][CH2:44][CH2:43][N:42]1[C:47]([O:49][C:50]([CH3:52])([CH3:51])[CH3:53])=[O:48]
Reactant: CC(C)(C)OC(=O)C[C@@H](CCCC1CCCCC1)C(=O)O
Reactant: CC(C)(C)OC(=O)N1CCCC[C@H]1/C(N)=N/O
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)C[C@@H](CCCC1CCCCC1)C(=O)O/N=C(\N)[C@@H]1CCCCN1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A solution of (2R)-2-(2-tert-butoxy-2-oxoethyl)-5-cyclohexylpentanoic acid (preparation 168) (500 mg, 1.67 mmol) in DCM (20 ml) was treated with HOBt (227 mg, 1.67 mmol), NMM (203 μl, 1.85 mmol) and WSCDI (354 mg, 1.85 mmol) followed by tert-butyl (2S)-2-[(Z)-amino(hydroxyimino)methyl]-1-piperidinecarboxylate (WO 9945006) (406 mg, 1.67 mmol) and stirred at room temperature, under a nitrogen atmosphere for 18 hours. H2O (10 ml) was added and after 10 minutes the reaction mixture was separated in a 5 micron filter cartridge. The solvent was removed under reduced pressure to afford the title compound as a colourless foam.
Reaction SMILES: [NH:1]([C:8]1[CH:16]=[C:15]([C:17](O)=[O:18])[C:14]([NH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:13][C:9]=1[C:10](O)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(=O)(O)(O)O.CO>O.C1C=C2C3N=C(C2=CC=1)N=C1C2C(C(=N1)N=C1C4C(C(=N1)N=C1C5C(C(=N1)N=3)=CC=CC=5)=CC=CC=4)=CC=CC=2.[Cu]>[CH:24]1[CH:25]=[C:26]2[C:17]([C:15]3[C:14]([NH:20][C:21]2=[CH:22][CH:23]=1)=[CH:13][C:9]1[C:10]([C:7]2[C:2]([NH:1][C:8]=1[CH:16]=3)=[CH:3][CH:4]=[CH:5][CH:6]=2)=[O:11])=[O:18]
Reactant: O=C(O)c1cc(Nc2ccccc2)c(C(=O)O)cc1Nc1ccccc1
Agent: [Cu]
Agent: O=P(O)(O)O
Agent: c1ccc2c(c1)C1=NC2=NC2=NC(=NC3=NC(=NC4=NC(=N1)c1ccccc14)c1ccccc13)c1ccccc12
Solvent: O
Solvent: CO
Product: O=c1c2ccccc2[nH]c2cc3c(=O)c4ccccc4[nH]c3cc12
Temperature: 95 °C
Reaction time: 0.25 h
Yield: 88.3 %

Procedure:
To 300 g of polyphosphoric acid (117% phosphoric acid) heated at 90° C. was added 0.7 g of copper phthalocyanine followed by 68.2 g of 2,5-dianilinoterephthalic acid. The mixture was heated at 120°-125° C. for two hours. After the melt was cooled to 95° C., the acid strength was adjusted to 112% by the dropwise addition of phosphoric acid. The resultant melt was stirred for 15 minutes and then slowly poured into 453 g of methanol at 24° C. During the drown, the temperature was allowed to increase to 55° C., with the temperature being controlled by external cooling and adjustment of melt addition rate. The slurry was heated at reflux (68°-72° C.) for one hour, diluted with water, and stirred at 60° C. for 30 minutes. The solid component was collected by filtration and washed with water until acid free. The resultant presscake was reslurried in water. After adjustment of the pH to greater than 7, 7.5 g of 50% sodium hydroxide was added and the resultant slurry was heated at 90° C. for one hour. The slurry was cooled, filtered, and washed with water until alkali free, then reslurried in water. After adjustment of the pH to greater than 8.5, 3.2 g of a cycloaliphatic carboxylic acid was added. The resultant slurry was heated at about 140°-145° C. for two hours in a closed system, cooled, acidified with phosphoric acid, and stirred. The solid component was collected by filtration and washed with water. The wet cake can be dried or used as is for specific applications. Here, the wet cake was dried in an oven at 60° C. to give approximately 54.0 g of quinacridone as a brilliant violet pigment.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6](SC)[N:5]=[C:4]([N:10]2[CH2:15][CH2:14][S:13](=[O:16])[CH2:12][CH2:11]2)[C:3]=1[N+:17]([O-:19])=[O:18].[CH3:20][CH2:21][O-:22].[Na+].[Na].[CH2:25]([OH:27])[CH3:26]>O>[CH2:21]([O:22][C:6]1[N:5]=[C:4]([N:10]2[CH2:15][CH2:14][S:13](=[O:16])[CH2:12][CH2:11]2)[C:3]([N+:17]([O-:19])=[O:18])=[C:2]([O:27][CH2:25][CH3:26])[N:7]=1)[CH3:20]
Reactant: CSc1nc(Cl)c([N+](=O)[O-])c(N2CCS(=O)CC2)n1
Reactant: CCO
Reactant: CC[O-]
Agent: [Na+]
Agent: [Na]
Solvent: O
Product: CCOc1nc(OCC)c([N+](=O)[O-])c(N2CCS(=O)CC2)n1
Reaction time: 20 h

Procedure:
3.0 gm (9.3 millimols) of 6-chloro-2-methylthio-5-nitro-4-(1-oxido-thiomorpholino)-pyrimidine (m.p. 128°-131°C) were added at room temperature to a sodium ethylate solution prepared from 0.22 gm (9.4 millimols) of sodium and 30 ml of ethanol, and the mixture was refluxed for 2 hours. After standing for 20 hours at room temperature, the reaction mixture was poured into water, the aqueous mixture was extracted several times with chloroform/ethanol, the combined extract solutions were evaporated to dryness, and the residue was recrystallized from ethyl acetate/petroleum ether. Yield: 2 gm (65% of theory); m.p. 130°-132°C.
Reaction SMILES: N[C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[ClH:11].[Cl:12]Cl.N([O-])=O.[Na+]>O.C(O)(C)C>[Cl:11][C:10]1[CH:2]=[C:3]([CH:7]=[C:8]([Cl:12])[CH:9]=1)[C:4]([OH:6])=[O:5]
Reactant: Nc1ccccc1C(=O)O
Reactant: ClCl
Reactant: Cl
Agent: O=N[O-]
Agent: [Na+]
Solvent: CC(C)O
Solvent: O
Product: O=C(O)c1cc(Cl)cc(Cl)c1
Yield: 83 %

Procedure:
137 parts of 2-aminobenzoic acid are introduced into 2,000 parts of 10 percent strength by weight hydrochloric acid. 138 parts of chlorine gas are passed in at 30° C. over 3 hours. 800 parts of isopropanol are then added. A solution of 100 parts of sodium nitrite in 140 parts of water is introduced in the coarse of 6 hours at 85° C.; nitrogen is evolved. The mixture is cooled and the product is filtered off. 158 parts (83% of theory) of 3,5-dichlorobenzoic acid of melting point 176°-179° C. are obtained.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2[N:16]=[C:17]([CH:25]3[CH2:28][CH2:27][CH2:26]3)[N:18]3[CH:23]=[CH:22][N:21]=[C:20](Cl)[C:19]=23)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:29]([NH2:32])([CH3:31])[CH3:30].CN1C(=[O:39])CCC1>>[CH:9]([OH:8])=[O:39].[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2[N:16]=[C:17]([CH:25]3[CH2:28][CH2:27][CH2:26]3)[N:18]3[CH:23]=[CH:22][N:21]=[C:20]([NH:32][CH:29]([CH3:31])[CH3:30])[C:19]=23)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Clc1nccn2c(C3CCC3)nc(-c3cccc(OCc4ccccc4)c3)c12
Reactant: CN1CCCC1=O
Reactant: CC(C)N
Product: CC(C)Nc1nccn2c(C3CCC3)nc(-c3cccc(OCc4ccccc4)c3)c12
Product: O=CO
Yield: 36 %

Procedure:
To a solution of 1-(3-benzyloxy-phenyl)-8-chloro-3-cyclobutyl-imidazo[1,5-a]pyrazine (30 mg, 0.075 mmol) in NMP (0.4 ml) was added isopropylamine (44 mg, 0.75 mmol). The reaction was irradiated in the microwave (200 W, 150° C., 5 min.) and then poured onto water (10 ml) and extracted with EtOAc (2×10 ml). The combined organics were washed with brine (3×10 ml), dried (MgSO4), filtered and evaporated to dryness. Purification by mass-directed HPLC gave [1-(3-Benzyloxy-phenyl)-3-cyclobutyl-imidazo[1,5-a]pyrazin-8-yl]-isopropyl-amine formic acid salt (11.0 mg, 36%) as a colorless solid: 1H NMR (400 MHz, CD3OD) δ 8.21 (s, 1H), 7.49 (d, 3H, J=8.2 Hz), 7.44-7.31 (m, 4H), 7.29 (s, 1H), 7.24-7.17 (m, 2H), 7.04 (d, 1H, J=5.1 Hz), 5.21 (s, 2H), 4.24-4.11 (m, 1H), 4.04-3.94 (m, 1H), 2.64-2.47 (m, 4H), 2.28-2.17 (m, 1H), 2.10-2.01 (m, 1H), 1.14 (d, 6H, J=6.7 Hz), 1H not observed (NH); LCMS (ES+) m/z 413.21 [MH+] at Rt 3.40 min.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=O)[CH2:9][CH2:10][CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][CH:16]([C:19]2[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=2)[CH2:15][CH2:14]1.Cl.[C:33]1([N:39]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)N)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:39]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:33]2[C:34]([C:9]=1[CH2:10][CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][CH:16]([C:19]3[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=3)[CH2:15][CH2:14]1)=[CH:35][CH:36]=[CH:37][CH:38]=2
Reactant: NN(c1ccccc1)c1ccccc1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCCCC(=O)c3ccccc3F)CC2)c1
Agent: Cl
Product: CC(C)C(=O)Nc1cccc(C2CCN(CCCc3c(-c4ccccc4F)n(-c4ccccc4)c4ccccc34)CC2)c1

Procedure:
Prepared by Procedure E and Scheme M using N-(3-{1-[5-(2-fluorophenyl)-5-oxopentyl]-4-piperidinyl}phenyl)-2-methylpropanamide and 1,1-diphenylhydrazine hydrochloride: ESMS m/e: 574.2 (M+H)+.
Reaction SMILES: C(OC([N:8]1[CH2:17][CH2:16][C:15]2[NH:14][N:13]=[C:12]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=3)[C:11]=2[CH2:10][CH2:9]1)=O)(C)(C)C.[F:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30]Br)=[CH:28][C:27]=1[CH3:34]>>[Cl:24][C:21]1[CH:20]=[CH:19][C:18]([C:12]2[C:11]3[CH2:10][CH2:9][NH:8][CH2:17][CH2:16][C:15]=3[N:14]([CH2:30][C:29]3[CH:32]=[CH:33][C:26]([F:25])=[C:27]([CH3:34])[CH:28]=3)[N:13]=2)=[CH:23][CH:22]=1
Reactant: Cc1cc(CBr)ccc1F
Reactant: CC(C)(C)OC(=O)N1CCc2[nH]nc(-c3ccc(Cl)cc3)c2CC1
Product: Cc1cc(Cn2nc(-c3ccc(Cl)cc3)c3c2CCNCC3)ccc1F
Yield: 1.9 %

Procedure:
The title compound (0.002 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C, 0.1 g) using 4-fluoro-3-methylbenzyl bromide (0.09 g) in place of benzyl chloride. MS (ESI): exact mass calculated for C21H21ClFN3, 369.14; found, m/z 370.1 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.49-7.47 (m, 2H), 7.45-7.42 (m, 2H), 7.07-7.01 (m, 1H), 7.00-6.95 (m, 1H), 6.95-6.90 (m, 1H), 5.31 (s, 2H), 2.97-2.91 (m, 4H), 2.89-2.84 (m, 2H), 2.82-2.77 (m, 2H), 2.22 (s, 3H).
Reaction SMILES: [C:1]([C:3]([CH3:11])([CH3:10])[CH:4]([OH:9])[CH2:5][C:6](O)=[O:7])#[N:2].Cl.C(OCC)(=O)C>C1COCC1>[C:1]([C:3]([CH3:11])([CH3:10])[CH:4]([OH:9])[CH2:5][CH2:6][OH:7])#[N:2]
Reactant: CC(C)(C#N)C(O)CC(=O)O
Agent: Cl
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C#N)C(O)CCO
Temperature: 25 °C
Reaction time: 3 h
Yield: 62 %

Procedure:
Optically active 4-cyano-3-hydroxy-4-methylpentanoic acid (1.5 g, 9.54 mmol) was dissolved in dry THF (5 mL) and a solution (38.175 mmol) of borane-THF complex was gradually added dropwise thereto at 0° C. After the completion of the dropwise addition, the mixture was stirred at room temperature for 3 hr and then 2N aqueous hydrochloric acid solution was added to neutralize the reaction mixture. Ethyl acetate (20 mL) was added thereto and the mixture was stirred vigorously. An organic layer was extracted. Ethyl acetate (20 mL) was further added to an aqueous layer and the mixture was stirred vigorously. The organic layer was extracted again. This step was repeated 3 times and the obtained organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give optically active 4-cyano-4-methyl-3-hydroxy-1-pentanol (847 mg, 5.915 mmol) (yield relative to optically active 4-cyano-3-hydroxy-4-methylpentanoic acid: 62%).
Reaction SMILES: [CH2:1]([N:3]1[C:9](=[O:10])[CH2:8][CH2:7][CH2:6][C:5]2[C:11]([O:18][CH3:19])=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=[CH:14][C:4]1=2)[CH3:2].CN(C)CCN(C)C.[I:28][Si](C)(C)C.II>C(Cl)Cl>[CH2:1]([N:3]1[C:9](=[O:10])[CH:8]([I:28])[CH2:7][CH2:6][C:5]2[C:11]([O:18][CH3:19])=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=[CH:14][C:4]1=2)[CH3:2]
Reactant: C[Si](C)(C)I
Reactant: CCN1C(=O)CCCc2c1ccc([N+](=O)[O-])c2OC
Agent: CN(C)CCN(C)C
Agent: II
Solvent: ClCCl
Product: CCN1C(=O)C(I)CCc2c1ccc([N+](=O)[O-])c2OC
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
1-Ethyl-6-methoxy-7-nitro-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (1.0 g) in Methylene chloride (12 mL) was cooled to 0° C. and treated with N,N,N′,N′-Tetramethylethylenediamine (1.7 mL) then treated dropwise with Iodotrimethylsilane (1.6 mL). A white precitate formed in the solution. The mixture was stirred at 0° C. for 30 min, solid Iodine (1.4 g) was added in one portion and the mixture stirred at 0° C. A dark color ensued. After 45 min, the reaction was quenched with 10% Na2S2O3, extracted with dichloromethane. The organic layers were washed with brine, dried (MgSO4), filtered and concentrated. (+/−)-1-Ethyl-3-iodo-6-methoxy-7-nitro-1,3,4,5-tetrahydro-benzo[b]azepin-2-one isolated as an orangish solid (1.30 g, 88%). LC/MS: (M+H)+ found 390.93. Taking on without purification.
Reaction SMILES: O[CH:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([C:11]([OH:13])=[O:12])[C:5]=2[CH2:4][CH2:3]1.S(Cl)([Cl:16])=O>C1C=CC=CC=1>[Cl:16][CH:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([C:11]([OH:13])=[O:12])[C:5]=2[CH2:4][CH2:3]1
Reactant: O=C(O)c1cccc2c1CCC2O
Reactant: O=S(Cl)Cl
Solvent: c1ccccc1
Product: O=C(O)c1cccc2c1CCC2Cl
Reaction time: 3 h

Procedure:
To 30 ml. of benzene is added 5.35 g. of 1-hydroxyindan-4-carboxylic acid. Following the addition of 15 ml. of thionyl chloride, the mixture is stirred fo 3 hours. Then, the reaction mixture is concentrated to dryness under reduced pressure and the resultant crystals are recrystallized from benzene. The described procedure gives 1-chloroindan-4-carboxylic acid melting at 135.5°-137.5°C.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6].[CH2:15]([NH:17][CH2:18][CH3:19])[CH3:16]>ClCCl>[CH2:15]([N:17]([CH2:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6])[CH2:18][CH3:19])[CH3:16]
Reactant: CCNCC
Reactant: O=C(CCCBr)OCc1ccccc1
Solvent: ClCCl
Product: CCN(CC)CCCC(=O)OCc1ccccc1
Yield: 60 %

Procedure:
A mixture of benzyl 4-bromobutanoate (58.6 diethylamine (58.3 g) and dichloromethane (1000 ml) was stirred under reflux for 14 hours. The reaction mixture was washed with water and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was subjected to column chromatography on silica gel. The fractions eluted with ethyl acetate gave benzyl 4-(N,N-diethylamino)butanoate (33.8 g, 60%).
Reaction SMILES: [F:1][C:2]1[C:7]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:6][CH:5]=[CH:4][C:3]=1[C:14](=[O:16])[CH3:15].C(=O)([O-])[O-].[K+].[K+].Br[CH2:24][CH2:25][O:26][CH3:27]>C(#N)C>[F:1][C:2]1[C:7]([CH:8]2[CH2:9][CH2:10][N:11]([CH2:24][CH2:25][O:26][CH3:27])[CH2:12][CH2:13]2)=[CH:6][CH:5]=[CH:4][C:3]=1[C:14](=[O:16])[CH3:15]
Reactant: CC(=O)c1cccc(C2CCNCC2)c1F
Reactant: COCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COCCN1CCC(c2cccc(C(C)=O)c2F)CC1

Procedure:
Preparation according to Example 1: 1-(2-fluoro-3-piperidin-4-ylphenyl)ethanone (0.01 g), acetonitrile (2 ml), potassium carbonate (0.01 g) and 1-bromo-2-methoxyethane (0.01 g). MS m/z (rel. intensity, 70 eV) 279 (M+, 1), 235 (16), 234 (bp), 163 (3), 133 (4).
Reaction SMILES: [C:1]1([C:7]2[C:8]([O:10][C:11](=[O:13])[CH:12]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:14]=[CH:15][CH:16]=[CH2:17]>C1(C)C=CC=CC=1>[C:1]1([C:7]23[C:8](=[O:9])[O:10][C:11](=[O:13])[CH:12]2[CH2:14][CH:15]=[CH:16][CH2:17]3)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C1C=C(c2ccccc2)C(=O)O1
Reactant: C=CC=C
Solvent: Cc1ccccc1
Product: O=C1OC(=O)C2(c3ccccc3)CC=CCC12
Temperature: 100 °C

Procedure:
A mixture of α-phenyl-maleic anhydride (20 g, 0.115 moles), butadiene (40 g, 0.74 moles) and 200 ml of toluene was heated at 100° C. in a sealed bomb for 15 hrs. The toluene solution was decanted from an insoluble, polymeric material and evaporated in vacuo to yield crude 1-phenyl-4-cyclohexene-1,2-dicarboxylic acid anhydride, bp 155° (0.3 mm).
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[O:12])[CH2:10][CH3:11])=[CH:5][CH:4]=1.C(O)(=O)C>Br(O)(=O)=O.C(OCC)(=O)C>[OH:2][C:3]1[CH:4]=[CH:5][C:6]([C:9](=[O:12])[CH2:10][CH3:11])=[CH:7][CH:8]=1
Reactant: CCC(=O)c1ccc(OC)cc1
Agent: [O-][Br+2]([O-])O
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CCC(=O)c1ccc(O)cc1
Temperature: 100 °C
Reaction time: 18 h
Yield: 69891.1 %

Procedure:
While 20 g (0.121 mmol) of 1-(4-methoxyphenyl)-1-propanone (7) prepared in Example 1-2 were added to 139 ml (2.4 mol) of acetic acid and stirred, 270 ml (2.4 mmol) of 48% bromic acid were added. Subsequently, the temperature was gradually increased to 100° C. and stirring under reflux was continued for 18 hr. The temperature was decreased to room temperature, and ethyl acetate was added, and organic layer was washed with water. Thereafter, the organic layer was washed with a saturated aqueous solution of potassium carbonate, then concentrated under reduced pressure, after which the precipitated solid was recrystallized with ethyl acetate/n-hexane system, and filtered, thus obtaining 12.7 g (yield: 70%) of a title compound (8) as a solid.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][CH:7]=1.Cl.[NH2:15][OH:16].C(=O)(O)[O-].[Na+]>CO>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:13]=[CH:12][C:9](/[C:10](=[N:15]/[OH:16])/[NH2:11])=[CH:8][CH:7]=1
Reactant: N#Cc1ccc(C2OCCO2)cc1
Reactant: NO
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Product: N/C(=N\O)c1ccc(C2OCCO2)cc1
Temperature: 25 °C
Yield: 82.1 %

Procedure:
A mixture of 4-(1,3-dioxolan-2-yl)benzonitrile (16.4 g, 93.6 mmol), hydroxylamine hydrochloride (9.76 g, 140 mmol) and sodium bicarbonate (15.7 g, 187 mmol) in MeOH (100 mL) was heated to reflux for 4 hr. After cooling to RT, the reaction mixture was filtered and the filtrate was concentrated to provide solids that were collected by filtration and washed with cold methanol to provide (Z)-4-(1,3-dioxolan-2-yl)-N′-hydroxybenzimidamide (16 g, 76.8 mmol). The compound had an HPLC retention time=0.38 min. —CHROMOLITH® SpeedROD 4.6×30 mm. flow=5 mL/min (2 min. gradient); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=209.2
Reaction SMILES: Br[CH2:2][CH:3]=[C:4]([CH2:14][CH3:15])[CH2:5][CH2:6][CH:7]=[C:8]([CH3:13])[CH2:9][CH:10]([CH3:12])[CH3:11].[CH2:16]1[O:20][C:19]2[CH:21]=[C:22]([OH:25])[CH:23]=[CH:24][C:18]=2[O:17]1>>[CH2:16]1[O:20][C:19]2[CH:21]=[C:22]([O:25][CH2:2][CH:3]=[C:4]([CH2:14][CH3:15])[CH2:5][CH2:6][CH:7]=[C:8]([CH3:13])[CH2:9][CH:10]([CH3:12])[CH3:11])[CH:23]=[CH:24][C:18]=2[O:17]1
Reactant: CCC(=CCBr)CCC=C(C)CC(C)C
Reactant: Oc1ccc2c(c1)OCO2
Product: CCC(=CCOc1ccc2c(c1)OCO2)CCC=C(C)CC(C)C

Procedure:
By the procedure of Example 1, 1-bromo-3-ethyl-7,9-dimethyl-2,6-decadiene is reacted with sesamol to obtain 1,2-(methylenedioxy-4-[(3-ethyl-7,9-dimethyl-2,6-decadienyl)-oxy]-benzene; nD24 = 1.5190.
Reaction SMILES: C([N:3]([CH2:6][CH3:7])[CH2:4]C)C.CN(C)[C:10]1([O:25][CH3:26])[CH:24]=CC(C(NC2C=CC=CC=2)=O)=[CH:12][CH2:11]1.C(Cl)(Cl)=O.[C:32]([NH:37][NH2:38])(=O)[CH:33]([CH3:35])[OH:34]>C(Cl)Cl.C1(C)C=CC=CC=1.CN(C)C=O>[CH3:26][O:25][C:10]1[CH:24]=[CH:7][C:6]([N:3]2[CH:4]=[N:38][N:37]=[C:32]2[CH:33]([CH3:35])[OH:34])=[CH:12][CH:11]=1
Reactant: CC(O)C(=O)NN
Reactant: CCN(CC)CC
Reactant: COC1(N(C)C)C=CC(C(=O)Nc2ccccc2)=CC1
Agent: O=C(Cl)Cl
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: COc1ccc(-n2cnnc2C(C)O)cc1
Temperature: -40 °C
Reaction time: 0.33 h

Procedure:
2.36 g of triethylamine were added to a suspension of 5 g of 4-dimethylamino-4-methoxy benzanilide (prepared as in Example 12) in 50 ml of methylene chloride and the mixture was cooled to -40° C. Then over 20 minutes and under an inert atmosphere, a solution of 5.75 ml of phosgene in toluene is added, and the mixture was re-heated to 20° C. over 90 minutes. The solution obtained was introduced into 200 ml of refluxing toluene and simultaneously a solution of 2.9 g of lactic acid hydrazide (DL form) in 6 ml of dimethylformamide was added. A part of the solvents was eliminated by distilling and then, after heating for 30 minutes to 107°-110° C., the reaction mixture was cooled and washed first with water, then with an N aqueous solution of sodium hydroxide and again with water. After extracting with methylene chloride and concentrating to dryness, 7.1 g of crude product were obtained which was crystallized from a mixture of ethyl acetylacetate and isopropyl ether (3-6) and then from pure ethyl acetate to obtain 5-[4-dimethylamino)phenyl]-4-(4-methoxyphenyl)-α-methyl-4H-1,2,4-triazol-3-methanol melting at 170° C.
Reaction SMILES: [C:1]1([Li])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:8]1[CH:13]=[CH:12]C(C)=[CH:10][CH:9]=1.Cl.C(=O)(O)[O-:17].[Na+]>O1CCCC1>[N:8]1[CH:13]=[CH:12][C:1]([CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][OH:17])=[CH:10][CH:9]=1
Reactant: Cc1ccncc1
Reactant: O=C([O-])O
Reactant: [Li]c1ccccc1
Agent: Cl
Agent: [Na+]
Solvent: C1CCOC1
Product: OCCCCCc1ccncc1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
Phenyl lithium (1.8 M cyclohexane diethyl ether, 27.6 mL, 0.0497 mol) is slowly added to a stirring solution of 4-picoline (4.6 g, 0.0497 mol) in 50 mL of tetrahydrofuran under nitrogen. The solution is stirred for 20 minutes at room temperature and then cooled to 0° C. 2-(4 Chlorobutoxy)-3,4,5,6-2H-tetrahydropyran (6.4 g, 0.0332 mol) is slowly adde to the reaction mixture and the mixture is stirred for 30 minutes at 0° C. The reaction mixture is refluxed for 12 hours, cooled, and 100 mL of 10% hydrochloric acid solution is added. The reaction mixture is stirred for another 12 hours and then made basic with a saturated solution of sodium bicarbonate and extracted with chloroform. The organic phase is dried (sodium sulfate) and evaporated in vacuo. The resulting residue is chromatographed on silica gel (ethyl acetate) to give 1.25 g of 5-(4-pyridinyl)-1 pentanol as a brown oil.