Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.[OH:11][C:12]1[CH:21]=[CH:20][C:15]([C:16]([O:18]C)=[O:17])=[CH:14][CH:13]=1>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:11][C:12]2[CH:21]=[CH:20][C:15]([C:16]([OH:18])=[O:17])=[CH:14][CH:13]=2)=[CH:4][CH:3]=1
Reactant: OB(O)c1ccc(F)cc1
Reactant: COC(=O)c1ccc(O)cc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: ClCCl
Product: O=C(O)c1ccc(Oc2ccc(F)cc2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 91.9 %

Procedure:
To a flask with 4-fluorophenyl boronic acid (2.1 g, 15 mmol), copper(II) acetate (1.4 g, 7.5 mmol), activated powdered molecular sieves (approximately 2 g), and methyl 4-hydroxybenzoate (1.2 g, 7.5 mmol) is added TEA (5.2 mL, 38 mmol) followed by CH2Cl2 (75 mL). The reaction is stirred for 16 hours at room temperature with air bubbling through it. The reaction mixture is diluted with CH2Cl2 and filtered through silica gel. The silica gel is washed with EtOAc-heptane. The solution is concentrated in vacuo and dissolved in dioxane (15 mL). To this solution is added aqueous LiOH (1N, 15 mL) and stirred for 18 hours at room temperature. To this reaction mixture is added aqueous HCl (1N) until acidic, having a pH less than 6. The resulting precipitate is collected by filtration and rinsed with water, and dried in vacuo to give 4-(4-fluorophenoxy)benzoic acid (1.6 g, 90%). MS for C13H9FO3 (ESI) (M−H)− m/z 231.
Reaction SMILES: [C:1]1(=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:8][CH2:9][CH:10]([OH:12])[CH3:11].C(O)(=O)C.C([BH3-])#N>CO>[CH:1]1([NH:8][CH2:9][CH:10]([OH:12])[CH3:11])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CC(O)CN
Reactant: O=C1CCCCC1
Agent: [BH3-]C#N
Solvent: CO
Solvent: CC(=O)O
Product: CC(O)CNC1CCCCC1

Procedure:
Cyclohexanone (0.98 g, 10 mmol) and 1-amino-propan-2-ol (0.75 g, 10 mmol) were mixed and MeOH (20 mL), acetic acid (12 mg, 0.5 mmol), cyanoborohydride resin (7 g, 14 mmol, 2 mmol/g, prepared as described by A. R. Sande et al, Tetrahedron Letters 1984, 3501) were added. The reaction mixture was heated under reflux for 16 h. The resin was filtered off and the filtrate was evaporated in vacuo. The crude product was used without further purification.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](Cl)=[O:10])=[CH:4][CH:3]=1.[NH:12]1[CH2:17][CH2:16][S:15](=[O:19])(=[O:18])[CH2:14][CH2:13]1>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([N:12]2[CH2:17][CH2:16][S:15](=[O:19])(=[O:18])[CH2:14][CH2:13]2)=[O:10])=[CH:4][CH:3]=1
Reactant: O=C(Cl)Cc1ccc(Br)cc1
Reactant: O=S1(=O)CCNCC1
Solvent: ClCCl
Product: O=C(Cc1ccc(Br)cc1)N1CCS(=O)(=O)CC1

Procedure:
A solution of 1.17 g (5 mmol) (4-Bromo-phenyl)-acetyl chloride (CAS 37859-24-8) in 25 ml CH2Cl2 is added dropwise to a solution of 710 mg (5.25 mmol) thiomorpholine 1,1-dioxide in 25 ml CH2Cl2. After complete addition, the reaction mixture is partitioned between water and CH2Cl2. The aqueous phase is re-extracted twice with CH2Cl2. The combined organic solution is washed with brine, dried over Na2SO4 and concentrated in vacuo to afford the title compound as a light yellow residue.
Reaction SMILES: [CH:1]([N:14]1[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][O:22][C:23]([C:25]2[CH:26]([C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([N+:43]([O-:45])=[O:44])[CH:38]=3)[C:27]([C:33]([O:35][CH3:36])=[O:34])=[C:28](O)[NH:29][C:30]=2[CH3:31])=[O:24])[CH2:16][CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:48])=O>>[CH:1]([N:14]1[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][O:22][C:23]([C:25]2[CH:26]([C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([N+:43]([O-:45])=[O:44])[CH:38]=3)[C:27]([C:33]([O:35][CH3:36])=[O:34])=[C:28]([Cl:48])[NH:29][C:30]=2[CH3:31])=[O:24])[CH2:16][CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)C1=C(O)NC(C)=C(C(=O)OCCN2CCN(C(c3ccccc3)c3ccccc3)CC2)C1c1cccc([N+](=O)[O-])c1
Reactant: O=P(Cl)(Cl)Cl
Product: COC(=O)C1=C(Cl)NC(C)=C(C(=O)OCCN2CCN(C(c3ccccc3)c3ccccc3)CC2)C1c1cccc([N+](=O)[O-])c1
Yield: 57.2 %

Procedure:
5-[2-(4-Benzhydrylpiperazin-1-yl)ethyl]oxycarbonyl-2-hydroxy-3-methoxycarbonyl-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine (390 mg) was dissolved in phosphorus oxychloride (5 ml) and the mixture was heated under reflux for 3 hours and 10 minutes. After excess phosphorus oxychloride had been distilled off under reduced pressure, the reaction mixture was diluted with saturated potassium carbonate and subjected to extraction with chloroform. The extract was distilled off and the residue was subjected to silica gel column chromatography (elution solvent: 1% chloroform/methanol), thereby obtaining crude crystals. This crude crystals were recrystallized from a solution of chloroform/isopropylether/hexane to yield 210 mg (57.2%) of the desired compound.
Reaction SMILES: [Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]#[N:13])[CH:10]=2)[CH:5]=[CH:4][C:3]=1[NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18].[H-].[Na+].[Cl:24][CH:25]=[CH:26][CH2:27]Cl>CN(C=O)C>[Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]#[N:13])[CH:10]=2)[CH:5]=[CH:4][C:3]=1[N:14]([CH2:27][CH:26]=[CH:25][Cl:24])[C:15](=[O:21])[O:16][C:17]([CH3:18])([CH3:20])[CH3:19]
Reactant: CC(C)(C)OC(=O)Nc1ccc2ccc(C#N)cc2c1Br
Reactant: ClC=CCCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N(CC=CCl)c1ccc2ccc(C#N)cc2c1Br
Temperature: 25 °C
Yield: 107.9 %

Procedure:
A solution of 194 (2.50 g, 7.21 mmol) in DMF (20 mL) was added to a suspension of NaH (350 mg, 8.65 mmol, 60% in oil) in DMF (20 mL) at 0° C. 1,3-Dichloropropene (1.60 g, 14 mmol) was added and the mixture was allowed to warm to room temperature over 2 h. The DMF was removed under reduced pressure and the residue was partitioned between CH2Cl2 and water. The organic layer was washed with water (×2), brine (×2) and dried. Filtration through silica gel gave tert-butyl 1-bromo-7-cyano-2-naphthyl(3-chloro-2-propen-1-yl)carbamate (195) (3.28 g, 100%) as a pale yellow oil; 1H NMR (CDCl3) (mixture of rotamers and E and Z forms) δ 8.73 (s, 1H), 7.93-7.96 (m, 1H), 7.83-7.87 (m, 1H, 7.68-7.70 (m, 1H), 7.39-7.46 (m, 1H), 6.00-6.11 (m, 2 H), 4.49-4.62 (m, 1H), 4.33-4.43 (m, 1H), 1.33, 1.32 (2's, 9 W. HRMS (FAB) calcd. for C19H1879Br35ClN2O2 (MH+) m/z 421.0318, found 421.0330.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[Cl:18])[NH:5][CH2:6][CH:7]([OH:14])[CH2:8][N:9]1[CH:13]=[CH:12][N:11]=[CH:10]1.[Cl:19][C:20]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:21]=1[CH2:22]Cl>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[Cl:18])[NH:5][CH2:6][CH:7]([O:14][CH2:22][C:21]1[CH:24]=[CH:25][C:26]([Cl:28])=[CH:27][C:20]=1[Cl:19])[CH2:8][N:9]1[CH:13]=[CH:12][N:11]=[CH:10]1
Reactant: ClCc1ccc(Cl)cc1Cl
Reactant: OC(CNc1ccc(Cl)c(Cl)c1)Cn1ccnc1
Product: Clc1ccc(COC(CNc2ccc(Cl)c(Cl)c2)Cn2ccnc2)c(Cl)c1

Procedure:
Reaction of 1-[3-(3,4-dichloroanilino)-2-hydroxypropyl]-imidazole with 2,4-dichlorobenzyl chloride yields 1-[3-(3,4-dichloroanilino)-2-(2,4-dichlorobenzyloxy)propyl]-imidazole. The base, purified by recrystallization from isopropanol, melts at 116°-117° C.; the methanesulfonate salt melts at 141°-143° C.
Reaction SMILES: Cl[CH2:2][CH2:3][C:4]1[C:5](=[O:19])[O:6][C:7]2[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[C:11]([O:17][CH3:18])[C:8]=2[C:9]=1[CH3:10].[OH:20][C:21]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>C(OCC)(=O)C.C(O)C>[OH:20][C:21]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:26][CH2:25][N:24]([CH2:2][CH2:3][C:4]2[C:5](=[O:19])[O:6][C:7]3[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[C:11]([O:17][CH3:18])[C:8]=3[C:9]=2[CH3:10])[CH2:23][CH2:22]1
Reactant: OC1(c2ccccc2)CCNCC1
Reactant: COc1cc(OC)c2c(C)c(CCCl)c(=O)oc2c1
Solvent: CCO
Solvent: CCOC(C)=O
Product: COc1cc(OC)c2c(C)c(CCN3CCC(O)(c4ccccc4)CC3)c(=O)oc2c1
Yield: 41 %

Procedure:
Process B; starting materials: 3-(2-chloroethyl)-5,7-dimethoxy-4-methyl-2H-1-benzopyran-2-one (Example 39) and 4-hydroxy-4-phenylpiperidine; yield 41%; m.p. 177.5°-179° C. (from ethyl acetate/ethanol).
Reaction SMILES: [CH2:1]([N:5]([CH2:44][CH2:45][CH2:46][CH3:47])[C:6]([C:8]1[CH:12]=[C:11]([CH3:13])[N:10]([C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-])=O)=[CH:16][C:15]=2[C:23]([N:25]2[C@H:34]([CH2:35][O:36][Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38])[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:26]2)=[O:24])[N:9]=1)=[O:7])[CH2:2][CH2:3][CH3:4]>CCO.[Pd]>[NH2:20][C:17]1[CH:18]=[CH:19][C:14]([N:10]2[C:11]([CH3:13])=[CH:12][C:8]([C:6]([N:5]([CH2:44][CH2:45][CH2:46][CH3:47])[CH2:1][CH2:2][CH2:3][CH3:4])=[O:7])=[N:9]2)=[C:15]([C:23]([N:25]2[C@H:34]([CH2:35][O:36][Si:37]([C:40]([CH3:42])([CH3:41])[CH3:43])([CH3:39])[CH3:38])[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:26]2)=[O:24])[CH:16]=1
Reactant: CCCCN(CCCC)C(=O)c1cc(C)n(-c2ccc([N+](=O)[O-])cc2C(=O)N2Cc3ccccc3C[C@H]2CO[Si](C)(C)C(C)(C)C)n1
Agent: [Pd]
Solvent: CCO
Product: CCCCN(CCCC)C(=O)c1cc(C)n(-c2ccc(N)cc2C(=O)N2Cc3ccccc3C[C@H]2CO[Si](C)(C)C(C)(C)C)n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of (S)—N,N-dibutyl-1-(2-(3-(((tert-butyldimethylsilyl)-oxy)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-nitrophenyl)-5-methyl-1H-pyrazole-3-carboxamide (3.0 g, 4.5 mmol) in EtOH (50 mL) was added 10% Pd—C(0.3 g) followed by stirring under H2 balloon pressure at RT for 3 h. The reaction mixture was filtered through celite, the bed was washed with EtOH (150 mL) and the filtrate was concentrated invacuo. The residue was purified on silica gel (100-200 mesh) to afford the title compound as an ‘off white’ solid 2.0 g (69%). Rf=0.45 (25% EtOAc in hexane); 1H NMR (400 MHz, DMSO-d6): δ 7.40-6.82 (m, 5H), 6.80-6.20 (m, 3H), 5.74-5.50 (m, 2H), 5.10-4.00 (m, 2H), 3.99-2.20 (m, 9H), 2.20-2.00 (m, 3H), 1.60-0.58 (m, 23H), 0.00-−0.04 (m, 6H); LC-MS: m/z 632.6 (M+H).
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[C:12]([O:16][C:17]([N:19]1[CH2:23][CH:22]=[CH:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].O>C(Cl)(Cl)Cl>[C:12]([O:16][C:17]([N:19]1[CH2:23][CH:22]2[O:9][CH:21]2[CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CC(C)(C)OC(=O)N1CC=CC1
Solvent: ClC(Cl)Cl
Solvent: O
Product: CC(C)(C)OC(=O)N1CC2OC2C1
Yield: 58.8 %

Procedure:
2.96 g (0.012 mole) of 70% aqueous m-chloroperbenzoic acid were added to a solution of 1.69 g (0.01 mole) of 1-t-butoxycarbonyl-3-pyrroline [prepared as described in Step (a) above] in 10 ml of chloroform, whilst ice-cooling, and the mixture was stirred with ice-cooling for 8 hours and then with water-cooling for 15 hours. At the end of this time, the reaction mixture was extracted with toluene and the extract was washed, in turn, with an aqueous solution of sodium bicarbonate, a 0.1N aqueous solution of sodium thiosulfate and water. It was then dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The residue was subjected to silica gel column chromatography eluted with a 1:5 by volume mixture of ethyl acetate and toluene, to afford 1.09 g of 1-t-butoxycarbonyl-3,4-epoxypyrrolidine as a colorless oily substance.
Reaction SMILES: [CH:1]1([N:5]2[CH2:10][CH2:9][N:8]([C:11]([C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17]([C:22]([N:24]3[CH2:29][CH2:28][S:27](=[O:31])(=[O:30])[CH2:26][CH2:25]3)=[O:23])=[CH:16]4)=[O:12])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[F:32][C:33]([F:44])([F:43])[C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[CH:38][CH:39]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH:1]1([N:5]2[CH2:6][CH2:7][N:8]([C:11]([C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[N:18]([C:38]3[CH:37]=[CH:36][CH:35]=[C:34]([C:33]([F:44])([F:43])[F:32])[CH:39]=3)[C:17]([C:22]([N:24]3[CH2:29][CH2:28][S:27](=[O:30])(=[O:31])[CH2:26][CH2:25]3)=[O:23])=[CH:16]4)=[O:12])[CH2:9][CH2:10]2)[CH2:2][CH2:3][CH2:4]1
Reactant: O=C(c1ccc2[nH]c(C(=O)N3CCS(=O)(=O)CC3)cc2c1)N1CCN(C2CCC2)CC1
Reactant: OB(O)c1cccc(C(F)(F)F)c1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=C(c1ccc2c(c1)cc(C(=O)N1CCS(=O)(=O)CC1)n2-c1cccc(C(F)(F)F)c1)N1CCN(C2CCC2)CC1
Yield: 60 %

Procedure:
The title compound was synthesized in analogy to example 66, from [5-(4-cyclobutyl-piperazine-1-carbonyl)-1H-indol-2-yl]-(1,1-dioxothiomorpholin-4-yl)-methanone (example 202), 3-(trifluoromethyl)phenylboronic acid, copper(II) acetate and pyridine in dichloromethane, to give the desired product as a colorless foam (60%).
Reaction SMILES: [CH3:1][C:2]1([CH3:8])[CH2:6][C:5](=[O:7])[CH:4]=[CH:3]1.[C-]#N.[K+].C[C:13]([OH:15])=[O:14]>CCO.O>[CH3:1][C:2]1([CH3:8])[CH2:6][C:5](=[O:7])[CH2:4][CH:3]1[C:13]([OH:15])=[O:14]
Reactant: CC1(C)C=CC(=O)C1
Reactant: CC(=O)O
Agent: [C-]#N
Agent: [K+]
Solvent: O
Solvent: CCO
Product: CC1(C)CC(=O)CC1C(=O)O
Temperature: 40 °C

Procedure:
To a solution of 4,4-dimethylcyclopent-2-enone (2.0 g, 18 mmol) in EtOH (50 mL), water (7.5 mL) and AcOH (1.5 mL) was added potassium cyanide (2.36 g, 36.3 mmol). The reaction mixture was heated to about 40° C. and after about 15 h the reaction mixture was concentrated under reduced pressure. The residue was diluted with EtOAc (50 mL) and washed with brine. The organic layer was separated, dried over anhydrous Na2SO4, filtered, and concentrated. The residue was dissolved in aqueous HCl (6N, 50 mL) and heated to reflux. After about 3 days the reaction mixture was cooled to room temperature and concentrated under reduced pressure to provide 2,2-dimethyl-4-oxocyclopentanecarboxylic acid (3.7 g, 90%, ˜70% purity by 1H NMR) that was carried on without additional purification: LC/MS (Table 2, Method a) Rt=1.30 min; MS m/z: 155 (M−H)−.
Reaction SMILES: [NH:1]([CH2:5][CH2:6][OH:7])[CH2:2][CH2:3][OH:4].C(=O)([O-])[O-].[Na+].[Na+].[CH2:14](Cl)[CH:15]=[CH2:16]>ClCCl>[CH2:16]([N:1]([CH2:5][CH2:6][OH:7])[CH2:2][CH2:3][OH:4])[CH:15]=[CH2:14]
Reactant: OCCNCCO
Reactant: C=CCCl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: C=CCN(CCO)CCO
Reaction time: 12 h
Yield: 102.5 %

Procedure:
A one liter, 3-necked, round bottomed flask, equipped with mechanical stirrer, dry ice condenser, thermometer and addition funnel (mounted atop condenser), was charged with diethanolamine (210.3 g, 2.0 mol). Finely ground sodium carbonate (17 g, 1.1 mol) was added to the flask. The amine was heated and stirred at 80° and the sodium carbonate dissolved. Allyl chloride (168.3 g, 2.2 mol) was added dropwise while keeping the reflux rate low and the temperature between 100° and 110° C. for between 2 and 3 hours. Stirring was continued at about 100° for 12 hours. The reaction mixture was allowed to cool and then diluted with dichloromethane (500 mL). The reaction mixture was then filtered. The residual salts in the reaction vessel were slurried with dichloromethane and filtered and finally all the salts were rinsed again with dichloromethane. The solvent was evaporated under reduced pressure to yield N-allyldiethanolamine (297.7 g, 102%) as a clear yellow oil. After cooling there was additional salt precipitation although the weight recorded was 297 g. Gas chromatographic analysis indicated that the product was approximately 90% pure. Distillation of the nearly pure material was conducted using a simple distillation head. Product boiling between 96° and 100° at 0.05 mL was collected affording 238 g (82% of the pure product):
Reaction SMILES: [OH:1][C:2]1[C:3]([N+:8]([O-:10])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.[CH3:11]N(C)C=O.C(=O)([O-])[O-].[K+].[K+].CI>O>[CH3:11][O:1][C:2]1[C:3]([N+:8]([O-:10])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=[N+]([O-])c1ncccc1O
Reactant: CN(C)C=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: O
Product: COc1cccnc1[N+](=O)[O-]
Reaction time: 8 h

Procedure:
A reaction flask was loaded with 3-hydroxy-2-nitropyridine (20 g), dimethylformamide (80 ml), and potassium carbonate (23.4 g), and they were mixed, followed by dropwise addition of methyl iodide (52.4 g) to the flask in 2.2 hours. After stirring overnight, water was added to this for crystallization. The crystals were filtrated for collection and dried to give 3-methoxy-2-nitropyridine (16.5 g).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5](Br)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].C([Li])CCC.[CH:19]([N:22]([CH:33]1[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1)[C:23](=[O:32])[C:24]1[CH:31]=[CH:30][C:27]([CH:28]=[O:29])=[CH:26][CH:25]=1)([CH3:21])[CH3:20].OS([O-])(=O)=O.[K+]>C(OCC)C.C1COCC1>[CH:33]1([N:22]([CH:19]([CH3:21])[CH3:20])[C:23](=[O:32])[C:24]2[CH:25]=[CH:26][C:27]([CH:28]([OH:29])[C:5]3[CH:4]=[C:3]([O:2][CH3:1])[C:8]([O:9][CH3:10])=[C:7]([O:11][CH3:12])[CH:6]=3)=[CH:30][CH:31]=2)[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38]1
Reactant: COc1cc(Br)cc(OC)c1OC
Reactant: CC(C)N(C(=O)c1ccc(C=O)cc1)C1CCCCC1
Agent: O=S(=O)([O-])O
Agent: [K+]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOCC
Product: COc1cc(C(O)c2ccc(C(=O)N(C(C)C)C3CCCCC3)cc2)cc(OC)c1OC
Temperature: -8 °C
Reaction time: 0.17 h

Procedure:
To a stirred, cold (-15° C.) solution of 3,4,5-trimethoxybromobenzene (965 mg, 3.9 mmol) in ethyl ether (15 ml) was added n-butyl lithium (3 ml of 1.6 M solution in hexane). The reaction mixture was stirred at -8° C. for 10 min., diluted with THF (5 ml) and warmed to 0° C. After stirring for 5 min., the reaction was cooled to -30° C. and a solution of terephthalaldehydic acid N-isopropyl-N-cyclohexyl amide (1.063 g, 3.9 mmol) in THF (5 ml) was added. After stirring at -30° C. for 10 min. and warming to room temperature, the reaction mixture was poured onto 0.5N KHSO4 and extracted with ethyl acetate. The organic layer was washed with saturated NaCl solution and dried (MgSO4). The drying agent was filtered and the filtrate concentrated in vacuo to give the crude product. This was chromatographed on silica gel using mixtures of ethyl acetate and hexane as eluents to give the title compound as a crystalline solid that could be recrystallized from cyclohexane containing a small amount of ethyl acetate, m. pt. 158-160° C.
Reaction SMILES: [OH:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:24][C:25]([CH3:27])=[CH2:26]>CS(C)=O>[OH:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:26][C:25]([CH3:27])=[CH2:24])=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1
Reactant: O=C(c1ccc(O)cc1)c1ccc(O)cc1
Reactant: C=C(C)CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: C=C(C)COc1ccc(C(=O)c2ccc(O)cc2)cc1
Temperature: 0 °C
Yield: 47 %

Procedure:
A solution of 14.6 grams (0.0682 mole) of 4,4'-dihydroxybenzophenone and 10.4 grams (0.0751 mole) of potassium carbonate in 250 mL of dimethyl sulfoxide was stirred under a nitrogen atmosphere for 20 minutes. To this was added during a 20 minute period via syringe 7.32 mL (0.0751 mole) of 3-chloro-2-methylpropene. Upon completion of addition the reaction mixture was heated at 60°-65° C. for 18 hours. The reaction mixture was poured into 600 mL of ice-water and then was extracted with four portions of diethyl ether. The combined ether extracts were washed with two 200 mL portions of aqueous 1N sodium hydroxide. The combined sodium hydroxide washes were made acidic with aqueous 20% hydrochloric acid. The resultant solid was dissolved in diethyl ether, and the solution was washed first with a saturated aqueous sodium chloride solution and then with water. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to yield 8.6 grams of 4-hydroxy-4'-(2-methyl-2-propenoxy)benzophenone.
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[C:3]1[CH:4]=[C:5]([CH:17]=[CH:18][CH:19]=1)[C:6]([C:8]([S:13]([CH3:16])(=[O:15])=[O:14])=[CH:9]N(C)C)=O.Cl.[F:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([NH2:30])=[NH:29])=[CH:26][CH:25]=1.C[O-].[Na+]>CO>[F:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]2[N:30]=[C:6]([C:5]3[CH:17]=[CH:18][CH:19]=[C:3]([C:2]([F:1])([F:20])[F:21])[CH:4]=3)[C:8]([S:13]([CH3:16])(=[O:14])=[O:15])=[CH:9][N:29]=2)=[CH:26][CH:25]=1
Reactant: CN(C)C=C(C(=O)c1cccc(C(F)(F)F)c1)S(C)(=O)=O
Reactant: N=C(N)c1ccc(F)cc1
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: CS(=O)(=O)c1cnc(-c2ccc(F)cc2)nc1-c1cccc(C(F)(F)F)c1
Yield: 81.1 %

Procedure:
6 g of 1-(3-trifluoromethylbenzoyl)-1-methane-sulfonyl-2-(N,N-dimethylamino)ethene and 4 g of 4-fluorobenzamidine hydrochloride were dissolved in 30 ml of methanol at room temperature. After adding 1.2 g of sodium methoxide thereto, the mixture was heated under reflux for 1 hour. The solvent was distilled away under reduced pressure. The residue was washed with water, and then dried to obtain 6 g of 2-(4-fluorophenyl)-4-(3-trifluoromethylphenyl)-5-methanesulfonylpyrimidine (Compound 112).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][N:3]=1.[OH-].[K+].[N+:12]([CH2:14][C:15]([N:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)=[O:16])#[C-:13]>CO>[Cl:1][C:2]1[CH:7]=[C:6]([C@@H:8]2[O:9][CH:13]=[N:12][C@H:14]2[C:15]([N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[O:16])[CH:5]=[CH:4][N:3]=1
Reactant: [C-]#[N+]CC(=O)N1CCCC1
Reactant: O=Cc1ccnc(Cl)c1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: O=C([C@@H]1N=CO[C@H]1c1ccnc(Cl)c1)N1CCCC1
Reaction time: 24 h
Yield: 66 %

Procedure:
SLA 07174 was prepared in accordance with method D using 2-chloropyridine-4-carbaldehyde SLA 07156 (0.12 g, 1.05 mmol), KOH (0.06 g, 1.05 mmol) in methanol (10 mL) and 2-isocyano-1-(pyrrolidin-1-yl)ethanone BLE 04098 (0.146 g, 1.05 mmol). The solution was stirred 24 h with continued cooling. After work-up trans-(5-(2-chloropyridin-4-yl)-4,5-dihydrooxazol-4-yl)(pyrrolidin-1-yl)methanone SLA 07174 was obtained as a yellow solid (0.19 g, 66% yield).
Reaction SMILES: [CH:1]1([C:6]2[CH:14]=[CH:13][C:9]([C:10]([OH:12])=O)=[CH:8][CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[NH2:46][CH2:47][C:48]1[C:49]([OH:56])=[N:50][C:51]([CH3:55])=[CH:52][C:53]=1[CH3:54]>ClCCl>[CH:1]1([C:6]2[CH:7]=[CH:8][C:9]([C:10]([NH:46][CH2:47][C:48]3[C:49]([OH:56])=[N:50][C:51]([CH3:55])=[CH:52][C:53]=3[CH3:54])=[O:12])=[CH:13][CH:14]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=C(O)c1ccc(C2CCCC2)cc1
Reactant: Cc1cc(C)c(CN)c(O)n1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1cc(C)c(CNC(=O)c2ccc(C3CCCC3)cc2)c(O)n1
Reaction time: 0.5 h
Yield: 21.6 %

Procedure:
To a solution of 4-cyclopentylbenzoic acid (95 mg, 0.5 mmol) in dichloromethane (20 mL) were added o-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (380 mg, 1 mmol) and triethylamine (202 mg, 2 mmol). The mixture was stirred for 0.5 hour. Then 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (120 mg, 0.8 mmol) was added. After stirring at room temperature for 4 hours, the mixture was washed with water (50 mL). Organic phase was separated and concentrated to give a residue. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=20:1) and to afford 4-cyclopentyl-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)benzamide (35 mg, 22%) as white solid. LRMS (M+H+) m/z: calcd 324.18. found 324. HPLC purity (214 nm): 100%. 1H NMR (300 MHz, CD3OD): δ 7.71 (d, J=8.1 Hz, 2H), 7.32 (d, J=8.1 Hz, 2H), 6.10 (s, 1H), 4.48 (s, 2H), 3.08-3.02 (m, 1H), 2.36 (s, 3H), 2.24 (s, 3H), 2.10-2.05 (m, 2H), 1.84-1.62 (m, 6H).