Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CCOP(OCC)([CH:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH3:7])=O.C([Li])CCC.[C:22]([O:26][C:27]([N:29]1[C@@H:33]([CH:34]=O)[CH2:32][O:31][C:30]1([CH3:37])[CH3:36])=[O:28])([CH3:25])([CH3:24])[CH3:23]>COCCOC>[C:22]([O:26][C:27]([N:29]1[C@@H:33](/[CH:34]=[C:6](/[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)\[CH3:7])[CH2:32][O:31][C:30]1([CH3:36])[CH3:37])=[O:28])([CH3:25])([CH3:23])[CH3:24]
Reactant: CCOP(=O)(OCC)C(C)c1ccccc1
Reactant: CC(C)(C)OC(=O)N1[C@@H](C=O)COC1(C)C
Agent: [Li]CCCC
Solvent: COCCOC
Product: C/C(=C\[C@H]1COC(C)(C)N1C(=O)OC(C)(C)C)c1ccccc1
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
A solution of diethyl 1-phenylethyl phosphonate (2.35 ml) in 1,2-dimethoxyethane (15 ml) was cooled under an argon atmosphere to 0° C. and treated dropwise with an n-butyllithium solution (5.9 ml; 1.6 M in hexane). The reaction mixture was stirred for 5 min at 0° C., then treated dropwise with a solution of (R)-4-formyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (1.5 g) in 1,2-dimethoxyethane (15 ml). The solution was warmed to r.t., then refluxed overnight. After cooling to r.t., the mixture was quenched with water and extracted with EtOAc. The organic layer was dried over MgSO4, filtrated and concentrated. The crude product was isolated by column chromatography (SiO2; gradient: cyclohexane ->cyclohexane/EtOAc 1:1) to give (S)-2,2-dimethyl-4-((E)-2-phenyl-propenyl)-oxazolidine-3-carboxylic acid tert-butyl ester (720 mg) as light yellow viscous oil.
Reaction SMILES: C1(N=C=NC2CCCCC2)CCCCC1.[C:16]([OH:24])(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[N:19][CH:18]=1.[CH2:25](O)[CH2:26][CH2:27][CH2:28][CH2:29]/[CH:30]=[CH:31]\[CH2:32]/[CH:33]=[CH:34]\[CH2:35]/[CH:36]=[CH:37]\[CH2:38][CH2:39][CH2:40][CH2:41][CH3:42]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:16]([O:24][CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]/[CH:37]=[CH:36]\[CH2:35]/[CH:34]=[CH:33]\[CH2:32]/[CH:31]=[CH:30]\[CH2:29][CH2:28][CH2:27][CH2:26][CH3:25])(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[N:19][CH:18]=1
Reactant: O=C(O)c1cccnc1
Reactant: CCCCC/C=C\C/C=C\C/C=C\CCCCCO
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CCCCC/C=C\C/C=C\C/C=C\CCCCCOC(=O)c1cccnc1
Yield: 91 %

Procedure:
1,3-Dicyclohexylcarbodiimide (97 g, 0.49 mol) and 4-(N,N-dimethylamino)pyridine (65 g, 0.53 mol) in methylene chloride (800 ml) were added with stirring to a solution of nicotinic acid (60 g, 0.49 mol) and z,z,z-octadeca-6,9,12-trienol (107 g, 0.41 mol) in methylene chloride (1200 ml). The progress of the reaction was monitored by tlc. On completion, the reaction mixture was filtered and the organic layer washed with 2M hydrochloric acid (500 ml) and water (3×500 ml), dried with magnesium sulphate and concentrated under reduced pressure. Purification by dry column chromatography using a gradient of ethyl acetate in hexane yielded z,z,z-octadeca-6,9,12-trienyl nicotinate as a pale yellow oil in 91% yield.
Reaction SMILES: [CH2:1]([C:4]1([CH:20]([CH3:22])[CH3:21])[O:9][C:8](=[O:10])[N:7]([CH:11]([C:13]2[CH:18]=[CH:17][C:16](Br)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].[F:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1B(O)O.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([C:4]1([CH:20]([CH3:22])[CH3:21])[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([C:27]3[CH:26]=[CH:25][C:24]([F:23])=[CH:29][C:28]=3[F:30])=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3]
Reactant: OB(O)c1ccc(F)cc1F
Reactant: C=CCC1(C(C)C)CCN(C(C)c2ccc(Br)cc2)C(=O)O1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1COCCO1
Product: C=CCC1(C(C)C)CCN([C@@H](C)c2ccc(-c3ccc(F)cc3F)cc2)C(=O)O1
Yield: 72.8 %

Procedure:
A mixture of 6-allyl-3-[1-(4-bromo-phenyl)-ethyl]-6-isopropyl-[1,3]oxazinan-2-one (200 mg, 0.55 mmol), 2,4-difluorophenylboronic acid (104 mg, 0.66 mmol), PdCl2(PPh3)2 (20 mg), aqueous Cs2CO3 solution (2 M, 2 mL) in 1,4-dioxane (8 mL) was heated to reflux for 2 h. The mixture was filtered, and the filtrate was extracted with EtOAc for 3 times. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated to give the crude product, which was purified by preparative TLC to give 6-allyl-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-isopropyl-1,3-oxazinan-2-one (160 mg, 73%). 1H NMR (CDCl3): 0.96 (m, 6H), 1.61 (m, 3H), 1.68-2.09 (m, 3H), 2.32-2.47 (m, 2H), 2.84 (m, 1H), 3.18 (m, 1H), 5.02-5.19 (m, 2H), 5.84 (m, 2H), 6.93 (m, 2H), 7.41 (m, 3H), 7.50 (m, 2H).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][CH:14]=1.C(Cl)(=O)C([Cl:25])=O>CN(C)C=O.C(Cl)Cl>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17]([Cl:25])=[O:18])=[CH:15][CH:14]=1
Reactant: O=C(O)c1ccc(OCc2ccc3ccccc3n2)cc1
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Cl)c1ccc(OCc2ccc3ccccc3n2)cc1

Procedure:
1.28 g of 4-(quinolin-2-ylmethoxy)benzoic acid, in 4.6 ml of oxalyl chloride and 3 drops of dimethylformamide are combined in 50 ml of methylene chloride. The mixture is refluxed for 30 minutes and then concentrated in vacuo to give 4-(quinolin-2-ylmethoxy)benzoyl chloride.
Reaction SMILES: [OH:1][CH2:2][C@H:3]1[CH2:7][S:6][C:5](=[O:8])[NH:4]1.[O:9]1[CH:14]=[CH:13][CH2:12][CH2:11][CH2:10]1.C(N(CC)CC)C>C(Cl)Cl.C1(C)C=CC(S(O)(=O)=O)=CC=1>[O:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]1[O:1][CH2:2][C@H:3]1[CH2:7][S:6][C:5](=[O:8])[NH:4]1
Reactant: O=C1N[C@@H](CO)CS1
Reactant: C1=COCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C1N[C@@H](COC2CCCCO2)CS1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 73.6 %

Procedure:
To a solution of 3-3 (3.3 g, 25 mmol) and 20 mg of p-toluenesulfonic acid in CH2Cl2 (100 mL) was added 3,4-dihydro-2H-pyran (2.7 mL, 30 mmol) and the resulting solution was stirred at rt for 30 minutes. Triethylamine (0.1 mL) was added and the solution was concentrated in vacuo. The compound was purified by flash chromatography using 40% EtOAc/hexanes to yield 4 g of 3-4 as a colorless oil. 1H NMR (400 MHz, acetone-d6): δ 7.0 (br s, 1H), 4.6 (s, 1H), 4.0 (m, 1H), 3.8 (m, 2H), 3.6 (m, 3H), 3.3 (dd, 1H), 1.9–1.4 (m, 6H).
Reaction SMILES: C([O:3][C:4](=[O:9])[C:5](=O)[CH2:6]Br)C.[F:10][C:11]([F:23])([F:22])[C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19]([NH2:21])=[S:20])=[CH:14][CH:13]=1>C(O)C>[F:23][C:11]([F:10])([F:22])[C:12]1[CH:13]=[CH:14][C:15]([NH:18][C:19]2[S:20][CH:6]=[C:5]([C:4]([OH:3])=[O:9])[N:21]=2)=[CH:16][CH:17]=1
Reactant: NC(=S)Nc1ccc(C(F)(F)F)cc1
Reactant: CCOC(=O)C(=O)CBr
Solvent: CCO
Product: O=C(O)c1csc(Nc2ccc(C(F)(F)F)cc2)n1
Temperature: 30 °C
Reaction time: 12 h

Procedure:
3-Bromo-2-oxo-propionic acid ethyl ester (0.59 mL) was added to a suspension of (4-trifluoromethyl-phenyl)-thiourea (1 grams), obtained in step (ii) of example-1, in ethanol (20 mL) and refluxed for about 12 hours. The reaction mixture was cooled and the solid obtained was filtered and dissolved in a minimum amount ethanol. 10% sodium hydroxide solution (10 mL) was added and stirred at about 25-35° C. for about 12 hours. The reaction mixture was then diluted with water and acidified with saturated citric acid solution. The solid that precipitated was filtered washed with water and dried to give the product (0.65 grams).
Reaction SMILES: [N:1]#[C:2]Br.[C:4]([O:8][C:9]([N:11]1[CH2:17][CH2:16][CH2:15][C@H:14]([NH:18][CH2:19][C:20]2[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22]([C:30]([F:33])([F:32])[F:31])[CH:21]=2)[C:13]2[CH:34]=[C:35]([CH2:42][CH3:43])[C:36]([C:38]([F:41])([F:40])[F:39])=[CH:37][C:12]1=2)=[O:10])([CH3:7])([CH3:6])[CH3:5].C(N(C(C)C)CC)(C)C>O1CCCC1>[C:4]([O:8][C:9]([N:11]1[CH2:17][CH2:16][CH2:15][C@H:14]([N:18]([CH2:19][C:20]2[CH:21]=[C:22]([C:30]([F:31])([F:33])[F:32])[CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:25]=2)[C:2]#[N:1])[C:13]2[CH:34]=[C:35]([CH2:42][CH3:43])[C:36]([C:38]([F:41])([F:39])[F:40])=[CH:37][C:12]1=2)=[O:10])([CH3:7])([CH3:6])[CH3:5]
Reactant: CCc1cc2c(cc1C(F)(F)F)N(C(=O)OC(C)(C)C)CCC[C@@H]2NCc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: N#CBr
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CCc1cc2c(cc1C(F)(F)F)N(C(=O)OC(C)(C)C)CCC[C@@H]2N(C#N)Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Temperature: 67.5 °C
Yield: 76.4 %

Procedure:
Add cyanogen bromide (0.352 g, 3.33 mmol) to a solution of (S)-5-(3,5-Bis-trifluoromethyl-benzylamino)-7-ethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester (0.647 g, 1.11 mmol) and diisopropylethylamine (0.679 mL, 3.89 mmol) in tetrahydrofuran (3 mL) at room temperature under nitrogen and heat the mixture at 65-70° C. for 16 hours and then for another 90° C. 16 h. Partition the cooled mixture between dichloromethane (40 mL) and brine (40 mL), separated layers. Extract aqueous with more dichloromethane (40 mL). Combine organic layers, dry over anhydrous sodium sulfate, filter and concentrated under reduced pressure. Purify the residue by column chromatography on silica gel, eluting with ethyl acetate/hexanes (0-20%), to provide the title compound (0.517 g, 76%), MS (ES+): 627 (M+NH4), 632 (M+Na).
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[F:20])=[CH:10][C:9]=1[NH:21][C:22](=[O:35])[CH2:23][C:24]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([N+:32]([O-:34])=[O:33])[CH:27]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[C:11]1[CH:12]=[CH:13][C:8]2[N:7]=[C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([N+:32]([O-:34])=[O:33])[CH:27]=3)[CH2:23][C:22](=[O:35])[NH:21][C:9]=2[CH:10]=1
Reactant: CC(C)(C)OC(=O)Nc1ccc(-c2ccccc2F)cc1NC(=O)CC(=O)c1cccc([N+](=O)[O-])c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C1CC(c2cccc([N+](=O)[O-])c2)=Nc2ccc(-c3ccccc3F)cc2N1

Procedure:
Prepared from {2′-fluoro-3-[3-(3-nitro-phenyl)-3-oxo-propionylamino]-biphenyl-4-yl }-carbamic acid tert.-butyl ester (Example K62) by treatment with TFA in CH2Cl2 according to the general procedure M. Obtained as a light yellow solid (62 mg).
Reaction SMILES: [C:1]1([C:7]#[C:8][C:9]2[CH:10]=[C:11]([C:23]([C:25]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=O)=O)[CH:12]=[C:13]([C:15]#[C:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:33]1([CH2:39][C:40]([CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[O:41])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C(O)CC.[OH-].C([N+](C)(C)C)C1C=CC=CC=1>C1(C)C=CC=CC=1>[C:1]1([C:7]#[C:8][C:9]2[CH:14]=[C:13]([C:15]3[C:16]([C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)=[C:42]([C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=4)[C:40](=[O:41])[C:39]=3[C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH:12]=[C:11]([C:23]#[C:25][C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(Cc1ccccc1)Cc1ccccc1
Reactant: O=C(C(=O)c1cc(C#Cc2ccccc2)cc(C#Cc2ccccc2)c1)c1ccccc1
Agent: C[N+](C)(C)Cc1ccccc1
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: CCCO
Product: O=C1C(c2ccccc2)=C(c2ccccc2)C(c2cc(C#Cc3ccccc3)cc(C#Cc3ccccc3)c2)=C1c1ccccc1
Temperature: 24 °C
Yield: 76.4 %

Procedure:
A portion of the 3,5-bis(phenylethynyl)benzil (10.87 grams, 0.0265 mole), 1,3-diphenylacetone (5.90 grams, 0.0281 mole), anhydrous 1-propanol (300 milliliters) and anhydrous toluene (17 milliliters), both of which had been sparged with dry nitrogen, were added under a dry nitrogen atmosphere to a predried 500 milliliter glass three neck round bottom reactor containing a predried magnetic stirring bar. The reactor was additionally outfitted with a fan cooled spiral condenser and a thermometer with thermostatically controlled heating mantle. Stirring and heating commenced, and once a refluxing clear light yellow colored solution formed, benzyltrimethylammonium hydroxide (40 percent in methanol) (0.91 gram) was added, immediately inducing a dark red color. After maintaining the reflux for 20 reactant had been achieved. After a cumulative 30 minutes of reaction, the heating mantle was removed from the reactor, and the stirred contents were maintained at 24° C. for the next 16 hours. The product was recovered via filtration through a medium fitted glass funnel. The product cake on the funnel was washed with two portions (50 milliliters) of 1-propanol, then dried in a vacuum oven to provide 11.84 grams (76.4 percent isolated yield) of 4-(3,5-bis(phenylethynyl)phenyl)-2,3,5-triphenylcyclopentadienone (unsymmetrically substituted 3,5-AAB monomer) as a dark red purple colored crystalline product. HPLC analysis revealed the presence of the desired product at 100 area percent. The product's identity was confirmed by 1H NMR and El MS analysis.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:17](=[O:18])[N:16]([CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[C:9]2[N:10]=[C:11]([S:14][CH3:15])[N:12]=[CH:13][C:8]=2[CH:7]=1)=[O:5])[CH3:2].C1(S(N2C(C3C=CC=CC=3)O2)(=O)=[O:31])C=CC=CC=1>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[C:17](=[O:18])[N:16]([CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[C:9]2[N:10]=[C:11]([S:14]([CH3:15])=[O:31])[N:12]=[CH:13][C:8]=2[CH:7]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1cc2cnc(SC)nc2n(C2CCCC2)c1=O
Reactant: O=S(=O)(c1ccccc1)N1OC1c1ccccc1
Solvent: ClCCl
Product: CCOC(=O)c1cc2cnc(S(C)=O)nc2n(C2CCCC2)c1=O
Reaction time: 24 h
Yield: 67.6 %

Procedure:
8-Cyclopentyl-2-methylsulfanyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (1.2 g, 3.6 mmol) was dissolved in CH2Cl2 (20 mL) and treated with 2-benzenesulfonyl-3-phenyl-oxaziridine (1.13 g, 4.32 mmol) at room temperature and stirred for 1 day. Following concentration under reduced pressure, the crude reaction mixture was chromatographed on silica gel eluting with ethyl acetate to give 8-cyclopentyl-2-methanesulfinyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester as a white solid (0.85 g, 68%). MS (APCI); M++1: Calc'd, 350.1. Found 350.0.
Reaction SMILES: [C:1]([O:5][CH2:6][CH3:7])(=[O:4])[CH2:2][CH3:3].[H-].[Na+].[CH:10](OCC)=[O:11].O>O1CCCC1>[CH3:3][CH:2]([CH:10]=[O:11])[C:1]([O:5][CH2:6][CH3:7])=[O:4]
Reactant: CCOC(=O)CC
Reactant: CCOC=O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)C(C)C=O
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 23.5 %

Procedure:
Into a 500-mL 3-neck round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of ethyl propionate (11.3 mL, 97.9 mmol) in tetrahydrofuran (160 mL). The solution was cooled to 0° C., then sodium hydride (4.1 g, 103 mmol, 60% dispersion in mineral oil) was added in portions. The mixture was stirred at 0° C. for 10 min, then ethyl formate (7.92 mL, 98.5 mmol) was added and the resulting mixture was stirred overnight at room temperature. The reaction was carefully quenched water (100 mL) by drop-wise addition and the mixture was extracted with ethyl acetate (2×100 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified by distillation under reduced pressure (50 mm Hg) and the fraction between 70-80° C. was collected to obtain the title compound as a colorless liquid (3.0 g, 24%).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[C:12]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[NH:11][C:10](=[O:26])[NH:9]2)=[CH:4][CH:3]=1.Cl[S:28]([OH:31])(=[O:30])=[O:29]>C(Cl)(Cl)Cl>[OH:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[C:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[C:12]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[NH:11][C:10](=[O:26])[NH:9]2)=[CH:6][C:7]=1[S:28]([OH:31])(=[O:30])=[O:29]
Reactant: O=C1NC(c2ccccc2)=C(c2ccccc2)C(c2ccc(O)cc2)N1
Reactant: O=S(=O)(O)Cl
Solvent: ClC(Cl)Cl
Product: O=C1NC(c2ccccc2)=C(c2ccccc2)C(c2ccc(O)c(S(=O)(=O)O)c2)N1
Temperature: 50 °C

Procedure:
To a solution of 4-(4-hydroxyphenyl)-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one (68 mg, 0.2 mmol) in CHCl3 (1 mL) was added ClSO3H (35 mg, 0.3 mmol). The mixture was heated to 50° C. overnight. The residue was purified by prep-HPLC to give Compound 123 as a white power (6 mg, 7%). 1H NMR (MeOH-d4 500 MHz): δ 7.75 (d, J=7.5 Hz, 1H), 7.38 (d, J=7 Hz, 1H), 7.30 (m, 2H), 7.24 (t, J=1, 5 Hz, 3H), 7.01 (t, J=3.5, 5 Hz, 3H), 6.87 (m, 3H), 5.23 (s, 1H); MS (ESI): m/z 423.0 [M+1]+.
Reaction SMILES: Br[C:2]1[CH2:6][CH2:5][CH2:4][C:3]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH3:13][S:14][C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1>>[C:7]1([C:3]2[CH2:4][CH2:5][CH2:6][C:2]=2[C:18]2[CH:19]=[CH:20][C:15]([S:14][CH3:13])=[CH:16][CH:17]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: BrC1=C(c2ccccc2)CCC1
Reactant: CSc1ccc(B(O)O)cc1
Product: CSc1ccc(C2=C(c3ccccc3)CCC2)cc1
Yield: 88.3 %

Procedure:
Following a synthetic procedure which was similar to the one outlined in Step 3 of Example 1, 750 mg (3.4 mmol) of 1-bromo-2-phenylcyclopentene (Step 1) was reacted with 1.2 g (6.8 mmol) of 4-methylthiophenylboronic acid (Example 1, Step 1). Purification by silica gel chromatography (MPLC) with hexane gave 800 mg (89%) of 1-(2-phenylcyclopenten-1-yl) -4-(methylthio)benzene as an oil: NMR (CDCl3) d 2.00-2.17 (m, 2H), 2.46 (s, 3H) , 2.86-3.01 (m, 4H) , 7.08-7.19 (m, 4H) , 7.19-7.32 (m, 5H) .
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][N:7]=1)[CH2:2][CH2:3][CH3:4].[CH3:13][N:14]1[C@H:28]2[C@@H:18]([C:19]3[CH:20]=[CH:21][CH:22]=[C:23]4[C:29]=3[C:26]([CH2:27]2)=[CH:25][NH:24]4)[CH2:17][C:16](=O)[CH2:15]1>[Pd]>[CH3:13][N:14]1[C@H:28]2[C@@H:18]([C:19]3[CH:20]=[CH:21][CH:22]=[C:23]4[C:29]=3[C:26]([CH2:27]2)=[CH:25][NH:24]4)[CH2:17][CH:16]([NH:12][C:9]2[CH:10]=[CH:11][C:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])=[N:7][CH:8]=2)[CH2:15]1
Reactant: CCCCOc1ccc(N)cn1
Reactant: CN1CC(=O)C[C@@H]2c3cccc4[nH]cc(c34)C[C@H]21
Agent: [Pd]
Product: CCCCOc1ccc(NC2C[C@@H]3c4cccc5[nH]cc(c45)C[C@H]3N(C)C2)cn1

Procedure:
The following compounds (isomers Ia and Ib) are obtained in a manner analogous to that described in Example 3, from 2-n-butoxy-5-aminopyridine and 6-methyl-8-oxo-ergoline in the presence of palladium:
Reaction SMILES: [NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:34][O:35][CH2:36][CH3:37])[N:14]([CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][O:23][CH2:24][CH2:25][P:26](=[O:33])([O:30]CC)[O:27]CC)[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.C[Si](Br)(C)C>C(Cl)Cl>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:34][O:35][CH2:36][CH3:37])[N:14]([CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][O:23][CH2:24][CH2:25][P:26](=[O:27])([OH:30])[OH:33])[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1
Reactant: CCOCc1nc2c(N)nc3ccccc3c2n1CCOCCOCCOCCP(=O)(OCC)OCC
Agent: C[Si](C)(C)Br
Solvent: ClCCl
Product: CCOCc1nc2c(N)nc3ccccc3c2n1CCOCCOCCOCCP(=O)(O)O
Temperature: 22 °C
Reaction time: 18 h

Procedure:
To a solution of diethyl (2-(2-(2-(2-(4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl)ethoxy)ethoxy)ethoxy)ethyl)phosphonate (1 equiv.) in CH2Cl2 (0.10 M) at 0° C. was slowly added trimethylsilyl bromide (10 equiv.). After 1 h the ice-bath was removed and the reaction mixture was allowed to stir at 22° C. for 18 h. At this point the volatiles were removed in vacuo and the resulting residue was purified by Reverse Phase-HPLC using a 20-90% 0.5 mM NH4OAc (in MeCN) to 10 mM NH4OAc (in water) gradient to deliver the title compound (26%) as a solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([F:9])[CH:3]=1.F[C:11]1[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+].O>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)=[C:4]([F:9])[CH:3]=1
Reactant: Oc1ccc(Cl)cc1F
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1ccc(Oc2ccc(Cl)cc2F)cc1
Temperature: 100 °C
Yield: 99.7 %

Procedure:
As shown in Scheme 1, a well stirred mixture of 4-chloro-2-fluorophenol (1) (14.62 g, 99.8 mmol), 1-fluoro-4-nitrobenzene (2) (12.80 g, 90.72 mmol) and sodium carbonate (19.23 g, 181.43 mmol) in DMF (100 mL) was heated at 100° C. for 12 h. LC/MS showed that the reaction was complete. The cooled reaction mixture was poured into 350 mL of water with stirring and extracted with 2×100 mL of dichloromethane. The combined organic layers were dried (MgSO4) and concentrated under reduced pressure to give the crude product. Purification by chromatography yielded 24.2 g (99%) of 4-chloro-2-fluoro-1-(4-nitrophenoxy)benzene (3) as a pale yellow solid. 1H NMR CDCl3: 8.25-8.18 (m, 2H); 7.28-7.15 (m, 3H); 7.08-6.97 (m, 2H). Unless otherwise indicated all NMR chemical shifts reported herein are denoted by the delta (δ) scale.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[C:3]=1[O:10][CH3:11].[Cl:12]CCOCCCl>C(O)(=O)C.O>[CH3:11][O:10][C:3]1[C:4]([O:8][CH3:9])=[CH:5][CH:6]=[C:7]([Cl:12])[C:2]=1[CH3:1]
Reactant: ClCCOCCCl
Reactant: COc1cccc(C)c1OC
Solvent: CC(=O)O
Solvent: O
Product: COc1ccc(Cl)c(C)c1OC
Yield: 67980.1 %

Procedure:
To a mixture of 25 g (0.16 mmol) of 1-methyl-2,3-dimethoxybenzene in 25 mL of acetic acid, was slowly added 26.4 g (0.33 mmol) of 1-chloromethylmethylether. The resultant reaction mixture was reacted overnight at 30° C. and then diluted with cold water, resulting in the formation of a precipitate. This precipitate was purified by recrystallization from hot hexanes and then reduced to dryness under reduced pressure to provide 20.3 g of a white solid (m.p. 69-70° C.).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](OCC)=[O:15])[N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C1COCC1.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([CH2:14][OH:15])[N:13]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)c1csc(NC(=O)OC(C)(C)C)n1
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)Nc1nc(CO)cs1
Reaction time: 24 h
Yield: 89 %

Procedure:
To a solution of ethyl 2-[(tert-butoxycarbonyl)amino]thiazole-4-carboxylate (27.3 g, 100 mmol) prepared by the method of Kim and Kahn (Synlett, 1999, 8, 1239-1240) in 500 mL of THF at 0 C was added a solution of Red-A1 in toluene (80 mL of 65 wt % solution) dropwise. The reaction mixture was stirred for 1 d and then quenched with water and 1N HCl. Extracted 2×EtOAc and the EtOAc extracts were dried over MgSO4. The solution was filtered, concentrated by rotary evaporator, and chromatographed on SiO2 using 33% hexanes in EtOAC to give 20.5 g (89%) of 2-[(tert-butoxycarbonyl)amino]-4-hydroxymethylthiazole 42a. 1H-NMR (400 MHz, CDCl3): δ 6.98 (s, 1H), 4.81 (s, 2H), 1.81 (s, 9H).
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].[C:14](Cl)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CN(C)C=O.C(OCC)(=O)C>[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:4][CH2:3]1
Reactant: OC1CCNCC1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: OC1CCN(C(c2ccccc2)(c2ccccc2)c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 22 h
Yield: 72.4 %

Procedure:
To a solution of 7.18 g (71 mmol) of 4-hydroxypiperidine in 100 ml dimethylformamide are added first 19.6 g (142 mmol) of powdered potassium carbonate and then 19.8 9 (71 mmol) of tritylchloride. The mixture is stirred for 22 hours at ambient temperature, diluted with ethyl acetate to twice the volume, washed with water and saturated saline solution, dried with magnesium sulphate and concentrated by evaporation. The residue is recrystallised from ethyl acetate/petroleum ether (1:4, v:v). 17.65 g (72.4% of theory) of 4-hydroxy-N-tritylpiperidine are obtained as colourless crystals, melting point 157-158° C.