Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([C:8]2([CH3:23])[CH2:10][N:9]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[N+:20]([O-:22])=[O:21])(=[O:13])=[O:12])[C:5]([F:24])=[CH:4][N:3]=1.[CH2:25]([O:27][C:28](=[O:36])[C@:29]([OH:35])([CH3:34])[C:30]([F:33])([F:32])[F:31])[CH3:26].[H-].[Na+]>CN(C=O)C>[CH2:25]([O:27][C:28](=[O:36])[C@:29]([O:35][CH2:10][C:8]([C:6]1[C:5]([F:24])=[CH:4][N:3]=[C:2]([Br:1])[CH:7]=1)([NH:9][S:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[N+:20]([O-:22])=[O:21])(=[O:13])=[O:12])[CH3:23])([CH3:34])[C:30]([F:31])([F:32])[F:33])[CH3:26]
Reactant: CC1(c2cc(Br)ncc2F)CN1S(=O)(=O)c1ccccc1[N+](=O)[O-]
Reactant: CCOC(=O)[C@@](C)(O)C(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)[C@@](C)(OCC(C)(NS(=O)(=O)c1ccccc1[N+](=O)[O-])c1cc(Br)ncc1F)C(F)(F)F
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 2-bromo-5-fluoro-4-[2-methyl-1-(2-nitro-benzenesulfonyl)-aziridin-2-yl]-pyridine (795 mg, 1.91 mmol) and (R)-3,3,3-trifluoro-2-hydroxy-2-methyl-propionic acid ethyl ester (498 mg, 2.67 mmol) in DMF (8 ml, soln. predried over mol. sieves) was added NaH (99 mg of a 60% dispersion in mineral oil, 2.48 mmol) and the reaction mixture was stirred at rt for 3 h. The reaction mixture was quenched with aq. 1N HCl and diluted with H2O and TBME. The phases were separated and the aq. phase was twice extracted with TBME. The combined org. phases were washed with H2O, dried over Na2SO4, filtered and concentrated. Flash chromatography on silica gel (heptane:EtOAc 1:1) yielded the title compound (diastereomer mixture) as a colourless solid. HPLC RtH4=1.26 min; ESIMS: 602, 604 [(M+H)+]; 1H NMR (400 MHz, CDCl3): δ 7.99 (m, 1H), 7.95-7.93 (m, 1H), 7.79-7.61 (m, 4H), 6.94 (m, 1H), 4.45-4.33 (m, 2H), 3.94-3.81 (m, 2H), 1.85 (m, 3H), 1.61 (m, 3H), 1.40-1.34 (m, 3H).
Reaction SMILES: CN(C)CCCN=C=NCC.[NH:12]1[C:16]2[CH2:17][CH2:18][CH:19]([C:21]([OH:23])=O)[CH2:20][C:15]=2[N:14]=[CH:13]1.ON1C2C=CC=CC=2N=N1.[CH3:34][S:35]([C:38]1[CH:45]=[CH:44][C:41]([CH2:42][NH2:43])=[CH:40][CH:39]=1)(=[O:37])=[O:36].C(N(C(C)C)C(C)C)C>CN(C=O)C>[CH3:34][S:35]([C:38]1[CH:45]=[CH:44][C:41]([CH2:42][NH:43][C:21]([CH:19]2[CH2:18][CH2:17][C:16]3[NH:12][CH:13]=[N:14][C:15]=3[CH2:20]2)=[O:23])=[CH:40][CH:39]=1)(=[O:36])=[O:37]
Reactant: O=C(O)C1CCc2[nH]cnc2C1
Reactant: CS(=O)(=O)c1ccc(CN)cc1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CS(=O)(=O)c1ccc(CNC(=O)C2CCc3[nH]cnc3C2)cc1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 81.1 %

Procedure:
At 0° C. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.23 g, 1.184 mmol) was added to a solution of 4,5,6,7-tetrahydro-1H-benzimidazole-5-carboxylic acid (024 g, 1.184 mmol) and 1-hydroxybenzotriazole (0.16 g, 1.184 mmol) in DMF (5 ml). The reaction mixture was stirred for 20 min at 0° C. 4-(Methylsulfonyl)benzylamine (0.26 g, 1.184 mmol) and ethyldiisopropylamine (0.90 ml, 5.211 mmol) were added successively. The reaction mixture was stirred for 16 hours, while it was warming up to room temperature. The solvent was removed in vacuo. The crude product was purified filtered through SepPack® (5 g), using 1% TFA in water/acetonitrile (80:40) as eluent. The resulting mixture was purified by flash chromatography on silica (40 g), using DCM/methanol/25% aqueous ammonia (50:10:1) as eluent, to give 0.32 g of the title compound.
Reaction SMILES: [CH3:1][CH:2]([O:9][N:10]1[C:15]([CH3:17])([CH3:16])[CH2:14][C:13](=O)[CH2:12][C:11]1([CH3:20])[CH3:19])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:21]([NH2:25])[CH2:22][CH2:23][CH3:24]>>[CH3:1][CH:2]([O:9][N:10]1[C:15]([CH3:17])([CH3:16])[CH2:14][CH:13]([NH:25][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:12][C:11]1([CH3:20])[CH3:19])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CC(ON1C(C)(C)CC(=O)CC1(C)C)c1ccccc1
Reactant: CCCCN
Product: CCCCNC1CC(C)(C)N(OC(C)c2ccccc2)C(C)(C)C1

Procedure:
The title compound, a colorless oil, is prepared from 1-alpha-methylbenzyloxy-2,2,6,6-tetramethylpiperidine-4-one and butylamine according to the procedure given in Example 35 except that acetonitrile is substituted for tetrahydrofuran and the molecular sieves are omitted.
Reaction SMILES: [Na].[CH2:2]([C:4]1[CH:5]=[CH:6][C:7]([CH:10]([CH2:27][OH:28])[CH2:11][O:12][C:13]2[CH:26]=[CH:25][C:16]([CH2:17][CH:18]3[S:22][C:21](=[O:23])[NH:20][C:19]3=[O:24])=[CH:15][CH:14]=2)=[N:8][CH:9]=1)[CH3:3].N1C=CC=CC=1.[C:35](OC(=O)C)(=[O:37])[CH3:36]>O>[C:35]([O:28][CH2:27][CH:10]([C:7]1[CH:6]=[CH:5][C:4]([CH2:2][CH3:3])=[CH:9][N:8]=1)[CH2:11][O:12][C:13]1[CH:14]=[CH:15][C:16]([CH2:17][CH:18]2[S:22][C:21](=[O:23])[NH:20][C:19]2=[O:24])=[CH:25][CH:26]=1)(=[O:37])[CH3:36]
Reactant: CC(=O)OC(C)=O
Reactant: CCc1ccc(C(CO)COc2ccc(CC3SC(=O)NC3=O)cc2)nc1
Agent: [Na]
Solvent: c1ccncc1
Solvent: O
Product: CCc1ccc(C(COC(C)=O)COc2ccc(CC3SC(=O)NC3=O)cc2)nc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 5-{4-[2-(5-ethyl-2-pyridyl)-3-hydroxypropoxy]benzyl}-2,4-thiazolidinedione sodium salt (408 mg), pyridine (10 ml) and acetic anhydride (0.15 ml) was stirred at room temperature for 8 hours, and poured in water, followed by extraction with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4) and freed of the solvent. The residue was chromatographed on a silica-gel (20 g) column and elution was effected with benzene-acetone (10:1, V/V) to give 5-{4-[3-acetoxy-2-(5-ethyl-2-pyridyl)propoxy]benzyl}-2,4-thiazolidinedione in the form of an oily substance. Yield of 350 mg (81.8%). IR(Neat): 1740, 1690, 1230 cm-1. NMR (CDCl3)δ: 1.24(3H,t,J=7 Hz), 2.00(3H,s), 2.64(2H,q,J=7 Hz), 3.03(1H,dd,J=14 and 9 Hz), 3.45(1H,dd,J=14 and 9 Hz), 3.60 (1H,m), 4.31(2H,d,J=5 Hz), 4.47(1H,dd,J=9 and 4 Hz), 4.55 (2H,d,J=5 Hz), 6.80(2H,d,J=9 Hz), 7.10(2H,d,J=9 Hz), 7.20(1H,d, J=8 Hz), 7.48(1H,dd,J=8 and 2 Hz), 8.42(1H,d,J=2 Hz).
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[S:10][CH:9]=[CH:8][C:6]=2[N:7]=1.C(O)(C(F)(F)F)=O.[CH3:19][C:20]1[CH:26]=[C:25]([CH3:27])[CH:24]=[C:23]([CH3:28])[C:21]=1[NH2:22]>C(Cl)Cl>[Cl:1][C:2]1[N:3]=[C:4]([NH:22][C:21]2[C:23]([CH3:28])=[CH:24][C:25]([CH3:27])=[CH:26][C:20]=2[CH3:19])[C:5]2[S:10][CH:9]=[CH:8][C:6]=2[N:7]=1
Reactant: Clc1nc(Cl)c2sccc2n1
Reactant: Cc1cc(C)c(N)c(C)c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1cc(C)c(Nc2nc(Cl)nc3ccsc23)c(C)c1
Temperature: 90 °C
Reaction time: 15 h
Yield: 23.2 %

Procedure:
To a solution of 2,4-dichlorothieno[3,2-d]pyrimidine (148 mg, 0.73 mmol), TFA (0.17 mL, 2.19 mmol) in TFE (2 mL) was added 2,4,6-trimethylaniline (0.15 mg, 1.1 mmol) in a sealed tube. The reaction was stirred at 90° C. for 15 h. The reaction mixture was diluted with CH2Cl2 and washed with saturated NaHCO3 solution (3×20 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography eluting with Hexanes:ethyl acetate (4:1) to afford the product as a white solid (51.4 mg, 23%):
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:22]2[CH2:27][C:26]([CH3:29])([CH3:28])[CH2:25][C:24]([CH3:31])([CH3:30])[CH2:23]2)[C:9]2[CH:14]=[CH:13][C:12](/[CH:15]=[CH:16]/[C:17]([O:19]CC)=[O:18])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[OH-].[Na+].Cl>C1COCC1.CCO>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:22]2[CH2:23][C:24]([CH3:31])([CH3:30])[CH2:25][C:26]([CH3:29])([CH3:28])[CH2:27]2)[C:9]2[CH:14]=[CH:13][C:12](/[CH:15]=[CH:16]/[C:17]([OH:19])=[O:18])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1
Reactant: CCOC(=O)/C=C/c1ccc(C(=C2CC(C)(C)CC(C)(C)C2)c2ccc(O)cc2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: CC1(C)CC(=C(c2ccc(O)cc2)c2ccc(/C=C/C(=O)O)cc2)CC(C)(C)C1
Temperature: 70 °C
Reaction time: 4.5 h
Yield: 83188.9 %

Procedure:
To a stirred solution of ethyl (2E)-3-{4-[(4-hydroxyphenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenyl}-2-propenoate (15) (7.75 g, 0.0185 mmol) in THF (100 mL) and EtOH (100 mL) was slowly added 1 N NaOH (93 mL) solution at RT. The reaction mixture was heated to 70° C. and stirred at that temperature for 4.5 h. Reaction mixture was cooled to room temperature and then poured into 20% aqueous HCl (350 mL). The product was separated out as an off-white solid. The suspension was filtered and the filtered solid was dried to afford 6.01 g (83%) of compound 16 as an off-white solid. mp 219-220° C. 1H NMR (300 MHz, DMSO-d6): δ 0.89 (s, 6H), 0.90 (s, 6H), 1.27 (s, 2H), 1.91 (s, 2H), 1.94 (s, 2H), 6.47 (d, J=15.9 Hz, 1H), 6.68 (d, J=8.1 Hz, 2H), 6.95 (d, J=8.4 Hz, 2H), 7.16 (d, J=8.1 Hz, 2H), 7.52 (d, J=15.9 Hz, 1H), 7.60 (d, J=8.1 Hz, 2H), 9.31 (s, 1H), 12.35 (s, 1H). LRMS (ESI): m/z 389 (M−H)−.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH:20]([C:23]1[CH:24]=[C:25]([CH:28]=[C:29]([CH:32]([CH3:34])[CH3:33])[C:30]=1[OH:31])[CH:26]=[O:27])([CH3:22])[CH3:21].O[CH2:36][CH2:37][N:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1.CCOC(/N=N/C(OCC)=O)=O>O1CCCC1>[CH:20]([C:23]1[CH:24]=[C:25]([CH:28]=[C:29]([CH:32]([CH3:34])[CH3:33])[C:30]=1[O:31][CH2:36][CH2:37][N:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1)[CH:26]=[O:27])([CH3:22])[CH3:21]
Reactant: OCCN1CCOCC1
Reactant: CC(C)c1cc(C=O)cc(C(C)C)c1O
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)c1cc(C=O)cc(C(C)C)c1OCCN1CCOCC1
Temperature: 25 °C
Reaction time: 12 h
Yield: 14.4 %

Procedure:
Triphenylphosphine (5.14 g, 19.58 mmol) was added to a solution of 3,5-diisopropyl-4-hydroxybenzaldehyde (4 g, 19.58 mmol) in tetrahydrofuran (40 ml) followed by addition of 2-hydroxyethylmorpholine (2.57 g, 19.58 mmol) and then the dropwise addition of diethylazodicarboxylate (3.41 g, 19.58 mmol). The mixture was stirred at room temperature for 12 hours. The reaction was concentrated under reduced pressure and partitioned between 2N hydrochloric acid (200 ml) and ethyl acetate (150 ml). The aqueous layer was extracted with ethyl acetate (2×150 ml), basified to pH 9 with solid sodium bicarbonate and extracted with ethyl acetate (3×150 ml). The organic layers were combined, dried over magnesium sulfate and concentrated to afford 900 mg (14%) of 3,5-diisopropyl-4-(2-morpholin-4-ylethoxy)-benzaldehyde as a yellowish oil.
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:12]=[N:13][CH:14]=2)=[CH:5][CH:4]=1.[H][H]>C(O)C.[Pd]>[F:20][C:2]([F:1])([F:21])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][NH:13][CH2:12][CH:11]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:10]2)=[CH:5][CH:4]=1
Reactant: CCOC(=O)c1cncc(-c2ccc(C(F)(F)F)cc2)c1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)C1CNCC(c2ccc(C(F)(F)F)cc2)C1

Procedure:
5.9 g (20.0 mmol) of ethyl 5-[4-(trifluoromethyl)phenyl]pyridine-3-carboxylate were dissolved in 140 ml of ethanol, 2.98 g Pd/C (10%) were added and the mixture was hydrogenated in an autoclave at 60° C. at a hydrogen pressure of 50 bar overnight. The reaction mixture was filtered through silica gel. The resulting solution was concentrated under reduced pressure. Water was added to the residue and the solution was adjusted to pH 8 using aqueous 1 N sodium hydroxide solution. The mixture was then extracted with dichloromethane. The organic phase was dried over sodium sulphate and concentrated. Yield: 4.2 g (67% of theory)
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[CH:10][C:11]2[O:15][C:14]([C:16]3[CH:21]=[CH:20][C:19]([CH:22](OC)[O:23]C)=[CH:18][C:17]=3[F:27])=[N:13][C:12]=2[CH:28]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl>C1COCC1.C(Cl)Cl>[CH2:1]([C:8]1[CH:9]=[CH:10][C:11]2[O:15][C:14]([C:16]3[CH:21]=[CH:20][C:19]([CH:22]=[O:23])=[CH:18][C:17]=3[F:27])=[N:13][C:12]=2[CH:28]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(OC)c1ccc(-c2nc3cc(Cc4ccccc4)ccc3o2)c(F)c1
Agent: Cl
Solvent: ClCCl
Solvent: C1CCOC1
Product: O=Cc1ccc(-c2nc3cc(Cc4ccccc4)ccc3o2)c(F)c1
Reaction time: 1 h

Procedure:
5-Benzyl-2-(4-(dimethoxymethyl)-2-fluorophenyl)benzo[d]oxazole (0.160 g, 0.424 mmol) was dissolved in 2 mL THF and 1 mL 5N HCl was added. The mixture was stirred for 1 h, diluted with DCM, and quenched with 10N NaOH until basic. The aqueous was extracted 2×DCM. Combined organics were dried over sodium sulfate, filtered, and concentrated to give 4-(5-benzylbenzo[d]oxazol-2-yl)-3-fluorobenzaldehyde as an orange solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.09 (s, 1H), 8.43 (t, J=7.3 Hz, 1H), 7.90-8.04 (m, 2H), 7.72-7.83 (m, 2H), 7.38 (d, J=8.5 Hz, 1H), 7.26-7.33 (m, 4H), 7.17-7.24 (m, 1H), 4.11 (s, 2H).
Reaction SMILES: ClC1SC(C[N:8]2[CH2:13][CH2:12][O:11][CH:10]([CH2:14][NH2:15])[CH2:9]2)=CC=1.[F:16][C:17]1[CH:18]=[C:19]([CH:22]=[CH:23][C:24]=1[F:25])[CH2:20]Br>>[F:16][C:17]1[CH:18]=[C:19]([CH:22]=[CH:23][C:24]=1[F:25])[CH2:20][N:8]1[CH2:13][CH2:12][O:11][CH:10]([CH2:14][NH2:15])[CH2:9]1
Reactant: Fc1ccc(CBr)cc1F
Reactant: NCC1CN(Cc2ccc(Cl)s2)CCO1
Product: NCC1CN(Cc2ccc(F)c(F)c2)CCO1

Procedure:
Intermediate 20 was prepared in an analogous manner to Intermediate 1 (Alternative Procedure) from Intermediate 19 and 3,4-difluorobenzyl bromide, followed by deprotection to yield the title compound.
Reaction SMILES: [CH2:1]([NH:11][C:12](=[O:22])[CH:13]=[CH:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([NH2:21])[CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[C:23]([OH:31])(=[O:30])[C:24]([CH2:26][C:27](O)=[O:28])=[CH2:25]>C(OCC)(=O)C>[CH2:1]([NH:11][C:12](=[O:22])[CH:13]=[CH:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N:21]2[CH2:25][CH:24]([C:23]([OH:31])=[O:30])[CH2:26][C:27]2=[O:28])[CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: C=C(CC(=O)O)C(=O)O
Reactant: CCCCCCCCCCNC(=O)C=Cc1cccc(N)c1
Solvent: CCOC(C)=O
Product: CCCCCCCCCCNC(=O)C=Cc1cccc(N2CC(C(=O)O)CC2=O)c1
Temperature: 25 °C

Procedure:
A mixture of 9.0 g. of N-decyl-3-(3-aminophenyl)-propenamide and 3.9 g. of itaconic acid was heated as a melt at 140°-145° C. for 1 hour, and then ca. 70 ml. of ethyl acetate was added to the hot mass. The resulting mixture was stirred and a solid appeared. The mixture was cooled to room temperature, and the solid was recovered by filtration to give 9.5 g. of the title compound. This produce was recrystallized from acetonitrile to give 8.4 g. (69% yield) of product having a melting point of 152.5°-153.5° C.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6].[OH:10][CH2:11][CH:12]([CH2:14]O)[OH:13].S(=O)(=O)(O)O.O>C1C=CC=CC=1>[OH:13][CH:12]1[CH2:11][O:10][CH:5]([C:4]2[CH:7]=[CH:8][CH:9]=[C:2]([CH3:1])[CH:3]=2)[O:6][CH2:14]1
Reactant: Cc1cccc(C=O)c1
Reactant: OCC(O)CO
Agent: O=S(=O)(O)O
Solvent: c1ccccc1
Solvent: O
Product: Cc1cccc(C2OCC(O)CO2)c1
Yield: 64.6 %

Procedure:
A mixture of 3-methylbenzaldehyde (24.0 g, 0.2 mole), glycerol (18.4 g, 0.2 mole) and 40% sulfuric acid (2.0 ml) in 150 ml of benzene was heated under a Dean-Stark apparatus until no more water was collected (approximately 2.5 hours). The mixture was cooled, neutralized with potassium carbonate, diluted by the addition of 200 ml of ether and the ether solution washed with water (3 × 100 ml). The organic layer was dried over magnesium sulfate and concentrated to give a residue of 25.1 g of the desired 5-hydroxy-2-(3-methylphenyl)-1,3-dioxane nD25 1.5346.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[SH:6].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:14][C:15]([O:17][CH3:18])=[O:16].O>CN(C=O)C>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6][CH2:14][C:15]([O:17][CH3:18])=[O:16]
Reactant: COC(=O)CBr
Reactant: Sc1cccs1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)CSc1cccs1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 78.6 %

Procedure:
To a solution of thiophene-2-thiol (1.2 g, 10.3 mmol) in anhydrous DMF (30 mL) was added cesium carbonate (3.9 g, 12 mmol) and the resulting suspension was stirred for 15 min at ambient temperature, then treated with methyl bromoacetate (1.53 g, 10 mmol). The purple suspension was stirred for 1 h, then poured into water (30 mL) and extracted twice with 300 mL EtOAc. The combined organic extracts were washed with brine, dried, filtered, concentrated and the residue was purified via column chromatography eluting with 10% EtOAc/Hexanes to give 1.48 g (79%) of the title compound.
Reaction SMILES: CN(C)C(=O)C.[NH2:7][C:8]1[CH:9]=[C:10]([CH:19]=[CH:20][C:21]=1[NH2:22])[C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:12].S([O-])(O)=O.[Na+].[CH:28]([C:30]1[NH:31][CH:32]=[CH:33][CH:34]=1)=O>O>[C:11]([C:10]1[CH:19]=[CH:20][C:21]2[N:22]=[C:28]([C:30]3[NH:31][CH:32]=[CH:33][CH:34]=3)[NH:7][C:8]=2[CH:9]=1)(=[O:12])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Nc1ccc(C(=O)c2ccccc2)cc1N
Reactant: O=Cc1ccc[nH]1
Agent: O=S([O-])O
Agent: [Na+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: O=C(c1ccccc1)c1ccc2nc(-c3ccc[nH]3)[nH]c2c1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 0.1 %

Procedure:
N,N-Dimethylacetamide (5 ml) was heated to 130° C., and 3,4-diaminobenzophenone (150 mg, 0.71 mol) and sodium hydrogensulfite (89 mg, 0.85 mol) were added and stirred for 5 minutes. 2-Formyl-pyrrole (81 mg, 0.85 mol) was added and stirred at 130° C. for 1.5 hours. The reaction mixture was allowed to cool to room temperature with stirring, and after addition of water to reaction mixture, precipitate was collected by filtration to afford 5-benzoyl-2-(pyrrol-2-yl)-benzimidazole (129 mg, 63%) as a pale yellow solid.
Reaction SMILES: [NH2:1][C:2]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:3]=1[O:4][C:5]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[CH2:7][CH2:8][N:9]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2.Br[CH2:28][CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[C:18]([O:17][C:15]([N:9]1[CH2:8][CH2:7][C:6]2[C:11](=[CH:12][CH:13]=[CH:14][C:5]=2[O:4][C:3]2[CH:22]=[C:23]([Cl:26])[CH:24]=[CH:25][C:2]=2[NH:1][CH2:28][CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:10]1)=[O:16])([CH3:20])([CH3:21])[CH3:19]
Reactant: CCOC(=O)CCCBr
Reactant: CC(C)(C)OC(=O)N1CCc2c(cccc2Oc2cc(Cl)ccc2N)C1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CCCNc1ccc(Cl)cc1Oc1cccc2c1CCN(C(=O)OC(C)(C)C)C2
Temperature: 60 °C
Reaction time: 3 h
Yield: 64.8 %

Procedure:
A mixture of 5-(2-amino-5-chlorophenoxy)-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinoline (2.92 g, 7.8 mmols), ethyl 4-bromobutyrate (2.2 ml, 15.6 mmols), potassium carbonate (1.08 g, 10 mmols) and N,N-dimethylformamide (10 ml) was stirred at 60° C. for 3 hours. The reaction mixture was cooled, then poured into water, and extracted with ethyl acetate. The extract was washed with water, and then dried with anhydrous magnesium sulfate. This was concentrated under reduced pressure, and the residue was purified through silica gel column chromatography to give an oil of ethyl 4-[2-[2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinolin-5-yloxy]-4-chlorophenyl]aminobutyrate (2.47 g, 64.8%).
Reaction SMILES: [CH:1]([NH:4][C:5]1[CH2:10][CH2:9][CH2:8][C:7](=[O:11])[CH:6]=1)([CH3:3])[CH3:2].O.[C:13]1(=[O:24])[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15](=[O:22])[C:14]1=[O:23]>C(Cl)(Cl)Cl>[OH:24][C:13]12[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[C:14]1([OH:23])[C:6]1[C:7](=[O:11])[CH2:8][CH2:9][CH2:10][C:5]=1[N:4]2[CH:1]([CH3:3])[CH3:2]
Reactant: CC(C)NC1=CC(=O)CCC1
Reactant: O=c1c(=O)c2ccccc2c1=O
Solvent: O
Solvent: ClC(Cl)Cl
Product: CC(C)N1C2=C(C(=O)CCC2)C2(O)C(=O)c3ccccc3C12O
Temperature: 25 °C
Reaction time: 12 h

Procedure:
Equimolar amounts of 3-isopropylaminocyclohex-2-enone and indanetrione hydrate (ninhydrin) were dissolved in chloroform and stirred at room temperature for 12 h. The solvent was then stripped off, and the oily residue was crystallized from acetone.
Reaction SMILES: C([C:3]1[CH:4]=[C:5](C2CCCCS2=O)[CH:6]=[CH:7][CH:8]=1)#N.C([C:18]1[CH:19]=[C:20]([CH2:24][S:25]([CH2:27][CH2:28][CH2:29][CH2:30][Cl:31])=[O:26])[CH:21]=[CH:22][CH:23]=1)#N>>[Cl:31][CH2:30][CH2:29][CH2:28][CH2:27][S:25]([CH2:24][C:20]1[CH:19]=[CH:18][C:23]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)=[CH:22][CH:21]=1)=[O:26]
Reactant: N#Cc1cccc(CS(=O)CCCCCl)c1
Reactant: N#Cc1cccc(C2CCCCS2=O)c1
Product: O=S(CCCCCl)Cc1ccc(-c2ccccc2)cc1

Procedure:
(±)-2-(3-cyanophenyl)tetrahydrothiopyran-1-oxide (mixture of cis/trans isomers), a colourless solid, melting point 116°-117° C., from (±)-3-cyano-1-[(4-chlorobutyl)sulphinylmethyl]benzene.
Reaction SMILES: [CH3:1][C:2](C)([O-])[CH3:3].[K+].[Br-].C([PH3+])CC.[N:12]1[CH:17]=[CH:16][C:15]([CH:18]=O)=[CH:14][CH:13]=1.O>C1COCC1>[CH2:18]([C:15]1[CH:16]=[CH:17][N:12]=[CH:13][CH:14]=1)[CH2:1][CH2:2][CH3:3]
Reactant: O=Cc1ccncc1
Reactant: CC(C)(C)[O-]
Agent: CCC[PH3+]
Agent: [Br-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: CCCCc1ccncc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 92.5 %

Procedure:
4-Butylpyridine was prepared by adding potassium-t-butoxide (0.68 g, 6 mmol) to propylphosphonium bromide (Aldrich) (2.4 g, 6.0 mmol) in THF (10 mL), at 0° C. and stirring at room temperature for 1 hour. Pyridine-4-carbaldehyde (428 mg, 4 mmol) was added and the reaction mixture stirred for 2 h. The reaction mixture was then poured into water and extracted with ethyl acetate. The product obtained after removing the solvent was taken as such in methanol (30 mL) to which palladium on carbon (10%, 300 mg) was added and hydrogenated at 1 atm pressure over night. Removal of solvent and purification on column chromatography using ethyl acetate resulted in pure product 4-butylpyridine (500 mg, 92%):
Reaction SMILES: [C:1]1([CH3:10])[C:2]([C:7](Cl)=O)=[CH:3][CH:4]=[CH:5][CH:6]=1.C=[CH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(N(CCCC)CCCC)CCC>C1(=O)CCCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:10][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]=[CH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: C=Cc1ccccc1
Reactant: Cc1ccccc1C(=O)Cl
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: CCCCN(CCCC)CCCC
Solvent: O=C1CCCCC1
Product: Cc1ccccc1C=Cc1ccccc1
Yield: 55.6 %

Procedure:
The procedure described in Example 1 is followed, except that 15.5 g (0.1 mol) of o-toluic acid chloride, 13 g (0.125 mol) of styrene, 23.2 g (0.125 mol) of tri-n-butylamine and 0.225 g (0.001 mol) of palladium acetate are used. After a reaction time of 4 hours at 120° C., in 100 ml of cyclohexanone as the solvent, 10.8 g (0.0556 mol) of 2-methylstilbene, corresponding to a yield of 55.6% of theory, are obtained; melting point 92°-93° C.
Reaction SMILES: [CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:9]([N:11]1[C:15]2[C:16]([NH2:25])=[C:17]([Cl:24])[C:18]([C:20]([F:23])([F:22])[F:21])=[CH:19][C:14]=2[N:13]=[C:12]1[CH3:26])[CH3:10].C1(S(O)(=O)=O)C=CC=CC=1>C1(C)C(C)=CC=CC=1>[CH:1](=[N:25][C:16]1[C:15]2[N:11]([CH2:9][CH3:10])[C:12]([CH3:26])=[N:13][C:14]=2[CH:19]=[C:18]([C:20]([F:22])([F:23])[F:21])[C:17]=1[Cl:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=Cc1ccccc1
Reactant: CCn1c(C)nc2cc(C(F)(F)F)c(Cl)c(N)c21
Agent: O=S(=O)(O)c1ccccc1
Solvent: Cc1ccccc1C
Product: CCn1c(C)nc2cc(C(F)(F)F)c(Cl)c(N=Cc3ccccc3)c21
Temperature: 25 °C
Yield: 94 %

Procedure:
Benzaldehyde (0.78 g.; 7.35 mmole) was reacted with 1-ethyl-2-methyl-5-trifluoromethyl-6-chloro-7-aminobenzimidazole (1.0 g.; 3.66 mmole) in the presence of 7 ml. of xylene and a few crystals of benzenesulfonic acid. The mixture was refluxed for 1 hour, removing water from the reaction mixture. Upon cooling to room temperature, the product crystallized out of solution to give 1.24 g. (94% yield). After recrystallization from benzene, the product melts at 183°-185.5° C.
Reaction SMILES: [CH:1]1[C:6]([CH:7]=O)=[CH:5][C:4]2[O:9][CH2:10][O:11][C:3]=2[CH:2]=1.[CH:12]1([NH2:18])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1>C1C=CC=CC=1>[CH2:10]1[O:11][C:3]2[CH:2]=[CH:1][C:6]([CH:7]=[N:18][CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]3)=[CH:5][C:4]=2[O:9]1
Reactant: NC1CCCCC1
Reactant: O=Cc1ccc2c(c1)OCO2
Solvent: c1ccccc1
Product: C(=NC1CCCCC1)c1ccc2c(c1)OCO2
Yield: 77.6 %

Procedure:
Piperonal (500 g) and cyclohexylamine (330 g) are dissolved in benzene, and the mixture is refluxed for about 3 hours while dehydrating with Diene Schtark device. The solvent is distilled off from the reaction mixture, and the residue is recrystallized from a mixture of isopropyl ether and hexane to give N-(3,4-methylenedioxybenzylidene)-N-cyclohexylamine (597 g).