Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]([CH:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13]3[S:14][CH:15]=[CH:16][CH:17]=3)=[CH:10][CH:11]=2)[CH2:6][CH2:5]1)=[N+]=[N-].O.O.[Sn](Cl)(Cl)(Cl)Cl>CO.C(OCC)(=O)C>[S:14]1[CH:15]=[CH:16][CH:17]=[C:13]1[C:9]1[CH:8]=[C:7]2[C:12](=[CH:11][CH:10]=1)[CH:4]([NH2:1])[CH2:5][CH2:6]2
Reactant: [N-]=[N+]=NC1CCc2cc(-c3cccs3)ccc21
Agent: Cl[Sn](Cl)(Cl)Cl
Solvent: O
Solvent: CCOC(C)=O
Solvent: CO
Product: NC1CCc2cc(-c3cccs3)ccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 70.4 %

Procedure:
5-(2-thienyl)-2,3-dihydro-1H-indene-1-yl)amine: To a solution of 2-(1-azido-2,3-dihydro-1H-indene-5-yl)thiophene (0.24 g, 0.99 mmol) in methanol (2mL) was added solid tin chloride dihydrate (0.45 g, 1.99 mmol) at room temperature under nitrogen. The reaction was stirred at room temperature overnight. The crude reaction mixture was poured into a separatory funnel and diluted with ethyl acetate (250 mL). The organic layer was washed with 2.0 N aqueous sodium hydroxide (50 mL), saturated aqueous sodium chloride (brine), and dried over anhydrous magnesium sulfate. Filtration, concentration and column chromatography on silica (9:1 dichloromethane/methanol) gave [5-(2-thienyl)-2,3-dihydro-1H-indene-1-yl]amine (0.15 g, 72% yield) as semi-solid: 1H NMR (400 MHz, CDCl3) 7.54 (m, 1H), 7.40 (d, 2H), 7.29 (m, 2H), 7.08 (m, 1H), 4.40 (t, 1H), 3.05 (m, 1H), 2.90 (m, 1H), 2.56 (m, 1H), 1.80 (m, 1H).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]1[NH:10][C:11]2[C:16]([C:17]=1[CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1)=[CH:15][CH:14]=[C:13]([C:24]([O:26][CH3:27])=[O:25])[CH:12]=2.C([O-])(=O)C.[Na+].C(O)(=O)C.[Cl:37][CH2:38][C:39](Cl)=[O:40]>O1CCCC1.O>[Cl:37][CH2:38][C:39]([NH:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]1[NH:10][C:11]2[C:16]([C:17]=1[CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1)=[CH:15][CH:14]=[C:13]([C:24]([O:26][CH3:27])=[O:25])[CH:12]=2)=[O:40]
Reactant: O=C(Cl)CCl
Reactant: COC(=O)c1ccc2c(C3CCCCC3)c(-c3ccc(C)cc3N)[nH]c2c1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Solvent: C1CCOC1
Product: COC(=O)c1ccc2c(C3CCCCC3)c(-c3ccc(C)cc3NC(=O)CCl)[nH]c2c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 91.1 %

Procedure:
To a suspension of methyl 2-(2-amino-4-methylphenyl)-3-cyclohexyl-1H-indole-6-carboxylate (638 mg, 1.6 mmol), sodium acetate (289 mg, 3.5 mmol) and acetic acid (0.10 ml, 1.8 mmol) in tetrahydrofuran (7 ml) was added dropwise chloroacetyl chloride (0.14 ml, 1.8 mmol), and the mixture was stirred at room temperature for 12 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure. The obtained crude product (640 mg) was used for Step 9 without further purification.
Reaction SMILES: [C:1]1([C:11]([C:13]2[N:17]([CH3:18])[CH:16]=[C:15]([C:19](=[O:21])[CH3:20])[CH:14]=2)=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Cl.[NH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.[CH2:29]=O.[OH-].[Na+]>CO>[C:1]1([C:11]([C:13]2[N:17]([CH3:18])[CH:16]=[C:15]([C:19](=[O:21])[CH2:20][CH2:29][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:14]=2)=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: C1CCNCC1
Reactant: CC(=O)c1cc(C(=O)c2cccc3ccccc23)n(C)c1
Reactant: C=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: Cn1cc(C(=O)CCN2CCCCC2)cc1C(=O)c1cccc2ccccc12
Temperature: 25 °C
Reaction time: 72 h
Yield: 81.2 %

Procedure:
A solution of 2.5 g (0.005 moles) of 1-[5-(1-naphthalenoyl)(1-methyl-1H-pyrrol-3-yl)]-1-ethanone, 1.1 g (0.0065 mole) of piperidine hydrochloride, and 1.0 g (0.0065 mole) paraformaldehyde in 50 mL of MeOH was heated at 65° C. for 48 h and stirred 72 h at room temperature, the reaction mixture was poured into 3N NaOH and extracted with Et2O. The organics were washed with water, brine and dried (Na2SO4). The solvent was evaporated in vacuo and the residue chromatographed on silica gel (95:5:0.5 CH2Cl2:MeOH:NH4OH). The resulting oil was treated with ethereal HCl to give 1.52 g (74%) of Compound 8. mp 141-143° C. CIMS m/z 375 (MH+). 1H NMR (300 MHz, DMSO-d6) δ 8.2 (Ar, 2H); 8.1-7.95 (Ar, 2H); 7.75-7.5 (Ar, 4H); 6.85 (Ar, 1H); 4.15 (s, 3H); 3.45-3.2 (m, 6H); 2.8 (bq, 2H); 1.7 (m, 5H); 1.85 (m, 1H). Anal calc'd for: C24H26N2O2.HCl.0.4H2O: Theory: C, 68.94; H,6.70; N, 6.70. Found: C, 69.12; H, 6.55; N, 6.70; KF water 1.63.
Reaction SMILES: [C:1](Cl)(=O)[C:2](Cl)=O.CS(C)=O.[CH:11]1[C:24]2[C:23]3([CH2:26][N:27]4[CH2:32][CH2:31][CH:30]([CH2:33][OH:34])[CH2:29][CH2:28]4)[CH2:25][CH:16]([C:17]4[C:22]3=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:15]=2[CH:14]=[CH:13][CH:12]=1.[CH2:35]([N:37](CC)[CH2:38]C)[CH3:36].[OH-].[Na+]>ClCCl>[CH:21]1[C:22]2[C:23]3([CH2:26][N:27]4[CH2:32][CH2:31][CH:30]([CH:33]([C:36]5[CH:35]=[N:37][CH:38]=[CH:1][CH:2]=5)[OH:34])[CH2:29][CH2:28]4)[CH2:25][CH:16]([C:15]4[C:24]3=[CH:11][CH:12]=[CH:13][CH:14]=4)[C:17]=2[CH:18]=[CH:19][CH:20]=1
Reactant: CCN(CC)CC
Reactant: OCC1CCN(CC23CC(c4ccccc42)c2ccccc23)CC1
Reactant: O=C(Cl)C(=O)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: ClCCl
Product: OC(c1cccnc1)C1CCN(CC23CC(c4ccccc42)c2ccccc23)CC1
Temperature: -60 °C
Reaction time: 0.25 h
Yield: 79.3 %

Procedure:
A solution of oxalyl chloride (3.86 g, 30.4 mmol) in dichloromethane (100 mL) was cooled to -60° C. and treated dropwise with dimethylsulfoxide (2.49 g, 31.89 mmol), resulting in vigorous gas evolution. The resulting mixture was stirred at -60° C. for 15 min, then was treated dropwise with a solution of 1-(9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)4-piperidinemethanol (6.47 g, 20.25 mmol) in dichloromethane (30 mL). This mixture was stirred at -60° C. for 1 h, then was treated with triethylamine (6.15 g, 60.75 mmol). The reaction was allowed to warm to room temperature, then was poured into 10% aqueous sodium hydroxide (50 mL) and extracted with chloroform (3×75 mL). The organic extracts were washed sequentially with 1N aqueous sodium hydroxide (50 mL) and brine (50 mL), combined, dried (K2CO3), filtered and evaporated to leave a tan solid. Trituration with hexane (50 mL) followed by filtration gave the title compound (5.09 g, 16.05 mmol, 79%) as a tan solid. 1H NMR (d6-DMSO): δ 9.57 (s, 1H, CHO), 7.28 (m, 2H), 7.17 (m, 2H), 6.91 (m, 4H), 4.30 (s, 1H, H-C(10)), 3.34 (s, 2H, CH2N), 2.86 (m, 2H, eq-H-C(2')), 2.45 (s, 2H, H-C(11)), 2.29 (m, 3H, ax-H-C(2'), H-C(4')), 1.76 (m, 2H, eq-H-C(3')), 1.45 (m, 2H, ax-H-C(3')).
Reaction SMILES: [NH:1]1[CH2:4][CH:3]([C:5]2[NH:9][N:8]=[C:7]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=3)[N:6]=2)[CH2:2]1.[Br:16][C:17]1[N:21]2[CH:22]=[C:23]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:24]([C:26]3[CH:33]=[CH:32][C:29]([CH:30]=O)=[CH:28][CH:27]=3)=[N:25][C:20]2=[N:19][C:18]=1[CH3:40].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>CN1C(=O)CCC1.C(O)(=O)C.C(N(CC)CC)C>[Br:16][C:17]1[N:21]2[CH:22]=[C:23]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)[C:24]([C:26]3[CH:27]=[CH:28][C:29]([CH2:30][N:1]4[CH2:4][CH:3]([C:5]5[N:6]=[C:7]([C:10]6[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=6)[NH:8][N:9]=5)[CH2:2]4)=[CH:32][CH:33]=3)=[N:25][C:20]2=[N:19][C:18]=1[CH3:40]
Reactant: c1ccc(-c2n[nH]c(C3CNC3)n2)nc1
Reactant: Cc1nc2nc(-c3ccc(C=O)cc3)c(-c3ccccc3)cn2c1Br
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CN1CCCC1=O
Solvent: CCN(CC)CC
Product: Cc1nc2nc(-c3ccc(CN4CC(c5n[nH]c(-c6ccccn6)n5)C4)cc3)c(-c3ccccc3)cn2c1Br
Reaction time: 1 h

Procedure:
147.6 mg 2-(5-Azetidine-3-yl-[1,2,4]triazole-3-yl)-pyridine×2HCl (intermediate example 44.0) are dissolved in 4.3 ml NMP. After addition of 0.16 ml triethylamine the reaction mixture is stirred for one hour. 192 mg (0.49 mmol) 4-(3-Bromo-2-methyl-6-phenylimidazo[1,2-a]pyrimidin-7-yl)benzaldehyde and 0.05 mL acetic acid are added and the reaction mixture is stirred for 23 hours at room temperature. 114.1 mg (0.54 mmol) NaBH(OAc)3, are added in portions and the reaction mixture is stirred at room temperature for three days. The reaction mixture is treated with 30 mL saturated NaHCO3 and stirred for 45 minutes. The precipitate is filtered off, washed with water and dried. After chromatography of the precipitate on silica gel (dichloromethane/methanol) 3.5 mg (1.2%) of the desired product are obtained.
Reaction SMILES: [N+:1](CCC)([O-:3])=[O:2].[O:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1.N12CCCN=C1CCC[CH2:14][CH2:13]2.C(=O)CC>C(OCC)(=O)C>[OH:7][CH:8]([CH2:13][CH3:14])[CH:9]([N+:1]([O-:3])=[O:2])[CH2:10][CH3:11]
Reactant: C1CCC2=NCCCN2CC1
Reactant: CCC[N+](=O)[O-]
Reactant: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CCC=O
Product: CCC(O)C(CC)[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 10 h
Yield: 84 %

Procedure:
Air in a reaction vessel was replaced with nitrogen, and 1-nitropropane (8.93 ml, 100 mmol) and dehydrated tetrahydrofuran (dry-THF) (50 ml) were added to the vessel. Then, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (1.5 ml, 10 mmol) was added to the mixture. After that, propionaldehyde (4.68 ml, 100 mmol) was added to the mixture while being was cooled on an ice bath. After the mixture had been stirred at room temperature for 10 hours, ethyl acetate (100 ml) was added to the mixture, and was washed with dilute hydrochloric acid, water, and a saturated salt solution, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure, whereby 4-hydroxy-3-nitrohexane was obtained (12.33 g, 84% yield).
Reaction SMILES: [Br:1][C:2]1[CH:30]=[CH:29][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:15]=[C:16]([CH:26]=[CH:27][CH:28]=3)[O:17][C:18]([CH3:25])([CH3:24])[C:19]([O:21]CC)=[O:20])[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.O1CCOCC1.[OH-].[Na+].Cl>CO>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:15]=[C:16]([CH:26]=[CH:27][CH:28]=3)[O:17][C:18]([CH3:25])([CH3:24])[C:19]([OH:21])=[O:20])[CH2:10][CH2:9]2)=[O:7])=[CH:29][CH:30]=1
Reactant: CCOC(=O)C(C)(C)Oc1cccc(N2CCN(C(=O)c3ccc(Br)cc3)CC2)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: CO
Product: CC(C)(Oc1cccc(N2CCN(C(=O)c3ccc(Br)cc3)CC2)c1)C(=O)O
Temperature: 25 °C
Reaction time: 2 h
Yield: 81 %

Procedure:
1.90 g (4.00 mmol) of ethyl [3-{4-(4-bromobenzoyl)piperazinyl}phenoxy]α,α-dimethylacetate was dissolved in a solvent mixture containing 20 ml of dioxane and 20 ml of methanol, to which 20 ml of aqueous 1N NaOH solution was added and stirred for 2 hours at room temperature. After completion of the reaction, diluted hydrochloric acid was added to the reaction mixture to convert the system to acidic, followed by extraction with chloroform, washing with water and drying over anhydrous sodium sulfate. Subsequently, chloroform was distilled off under reduced pressure. The oily residue obtained was crystallized from a solvent mixture of petroleum ether, ether and ethyl acetate to obtain 1.45 g (81.0%) of the target compound as colorless crystals.
Reaction SMILES: [C:1]([C:3]1([C:6]2[CH:7]=[C:8]([CH:36]=[CH:37][CH:38]=2)[C:9]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]3[CH:20]=[N:21][C:22]([NH:25][S:26]([C:29]4[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=4)(=[O:28])=[O:27])=[CH:23][CH:24]=3)[CH:13]=2)=[O:10])[CH2:5][CH2:4]1)#[N:2].C(N(CC)C(C)C)(C)C.I[CH2:49][C:50]([NH2:52])=[O:51]>CN(C)C=O>[NH2:52][C:50](=[O:51])[CH2:49][N:21]1[C:22](=[N:25][S:26]([C:29]2[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=2)(=[O:27])=[O:28])[CH:23]=[CH:24][C:19]([O:18][C:14]2[CH:13]=[C:12]([NH:11][C:9](=[O:10])[C:8]3[CH:36]=[CH:37][CH:38]=[C:6]([C:3]4([C:1]#[N:2])[CH2:5][CH2:4]4)[CH:7]=3)[CH:17]=[CH:16][CH:15]=2)=[CH:20]1
Reactant: NC(=O)CI
Reactant: Cc1ccc(S(=O)(=O)Nc2ccc(Oc3cccc(NC(=O)c4cccc(C5(C#N)CC5)c4)c3)cn2)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Cc1ccc(S(=O)(=O)N=c2ccc(Oc3cccc(NC(=O)c4cccc(C5(C#N)CC5)c4)c3)cn2CC(N)=O)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 77.1 %

Procedure:
To a solution of 3-(1-cyanocyclopropyl)-N-{3-[(6-{[(4-methylphenyl)sulfonyl]amino}pyridin-3-yl)oxy]phenyl}benzamide (2.5 g, 4.77 mmol) in N,N-dimethylformamide (15 mL) was added N,N-diisopropylethylamine (0.90 mL, 5.01 mmol), and the mixture was stirred at room temperature for 15 min. 2-Iodoacetamide (927 mg, 5.01 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 48 hr. The reaction mixture was concentrated under reduced pressure, water (150 mL) was added to the residue, and the mixture was extracted with ethyl acetate (150 mL). The organic layer was washed with saturated brine (150 mL) and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was recrystallized from ethyl acetate and hexane to give the title compound (2.14 g, 77%) as a pale-yellow solid.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:10]=[C:9](Br)[C:8]2[N:12]=[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[O:14][C:7]=2[C:6]=1[OH:21])=[O:4].C([Sn](CCCC)(CCCC)[C:27]#[C:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)CCC>>[CH3:1][O:2][C:3]([C:5]1[N:10]=[C:9]([C:27]#[C:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:8]2[N:12]=[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[O:14][C:7]=2[C:6]=1[OH:21])=[O:4]
Reactant: COC(=O)c1nc(Br)c2nc(-c3ccccc3)oc2c1O
Reactant: CCCC[Sn](C#Cc1ccccc1)(CCCC)CCCC
Product: COC(=O)c1nc(C#Cc2ccccc2)c2nc(-c3ccccc3)oc2c1O

Procedure:
Prepared from 4-bromo-7-hydroxy-2-phenyl-oxazolo[4,5-c]pyridine-6-carboxylic acid methyl ester, example 3a, and tributyl(phenylethynyl)tin under conditions analogous to experimental example 3b. MS: (+) m/z 370.9 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[CH2:5][NH:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:9]([C:10]([OH:12])=O)[C:8]=1[C:16]([OH:18])=O.Cl.[NH2:23][C:24]1([CH3:32])[CH2:29][CH2:28][C:27](=[O:30])[NH:26][C:25]1=[O:31]>N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[CH2:5][NH:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:9]2[C:8]=1[C:16](=[O:18])[N:23]([C:24]1([CH3:32])[CH2:29][CH2:28][C:27](=[O:30])[NH:26][C:25]1=[O:31])[C:10]2=[O:12]
Reactant: O=C(O)c1cccc(NCc2cccc(Cl)c2)c1C(=O)O
Reactant: CC1(N)CCC(=O)NC1=O
Agent: Cl
Solvent: c1ccncc1
Product: CC1(N2C(=O)c3cccc(NCc4cccc(Cl)c4)c3C2=O)CCC(=O)NC1=O
Yield: 40.7 %

Procedure:
To a stirred solution of 3-(3-Chloro-benzylamino)-phthalic acid (4 mmol) in pyridine (50 ml) was added 3-amino-3-methyl-piperidine-2,6-dione hydrochloride (0.71 g, 4 mmol). The reaction mixture was heated to reflux for 18 h. The solvent was evaporated in vacuo and the residue dissolved in methylene chloride (150 ml). The methylene chloride mixture was washed with water (2×100 ml), 0.1N HCl (2×100 ml), brine (1×100 ml), dried (magnesium sulfate), and filtered. The solvent was evaporated in vacuo to give a yellow semi-solid. The residue was purified by preparative HPLC (Symmetry C18, isocratic, 50% acetonitrile/water) to give 0.67 g (41%) of product as a yellow solid: mp 199-201° C.; 1H NMR (DMSO-d6) δ 10.99 (s, 1H), 7.52-7.28 (m, 6H), 6.97-6.89 (m, 2H), 4.54 (d, J=6.1 Hz, 1H), 2.78-2.50 (m, 3H), 2.08-1.98 (m, 1H), 1.89 (s, 3H); 13C NMR (DMSO-d6) δ 172.42, 172.19, 169.62, 167.92, 145.59, 141.82, 136.02, 133.14, 132.06, 130.35, 126.91, 126.78, 125.60, 117.23, 110.42, 109.49, 58.37, 44.74, 29.27, 28.62, 21.02; Anal. Calcd. For C21H18ClN3O4: C, 61.24; H, 4.41; N, 10.20. Found: C, 61.30; H, 4.28; N, 9.97.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15]([C:17]1[S:21][C:20]2[CH:22]=[CH:23][C:24]([O:26][CH2:27][CH2:28][CH2:29][N:30]([CH3:32])[CH3:31])=[CH:25][C:19]=2[CH:18]=1)=[O:16])(C)(C)C.NC1C=CC=CC=1NC(C1SC2C=CC(OCCN(C)C)=CC=2C=1)=O>>[NH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15]([C:17]1[S:21][C:20]2[CH:22]=[CH:23][C:24]([O:26][CH2:27][CH2:28][CH2:29][N:30]([CH3:31])[CH3:32])=[CH:25][C:19]=2[CH:18]=1)=[O:16]
Reactant: CN(C)CCCOc1ccc2sc(C(=O)Nc3ccccc3NC(=O)OC(C)(C)C)cc2c1
Agent: CN(C)CCOc1ccc2sc(C(=O)Nc3ccccc3N)cc2c1
Product: CN(C)CCCOc1ccc2sc(C(=O)Nc3ccccc3N)cc2c1

Procedure:
was prepared from (2-{[5-(3-Dimethylamino-propoxy)-benzo[b]thiophene-2-carbonyl]-amino}-phenyl)-carbamic acid tert-butyl ester (7) in an analogous manner to that described for the preparation of (1) example 1, step 5; white solid, mp. 164–167° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH3:11])[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.[C:12]1([CH2:18][CH2:19][CH2:20][CH2:21]Br)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[CH3:10][O:9][C:7]1[CH:6]=[C:5]([CH3:11])[CH:4]=[C:3]([O:2][CH3:1])[C:8]=1[CH2:21][CH2:20][CH2:19][CH2:18][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: COc1cc(C)cc(OC)c1
Reactant: BrCCCCc1ccccc1
Product: COc1cc(C)cc(OC)c1CCCCc1ccccc1
Yield: 1347.9 %

Procedure:
3,5-Dimethoxytoluene (2.93 mL, 20 mmol) and 4-phenylbutylbromide (4.13 mL, 1.2 mmol) were reacted as described under General Procedure H and the crude product was purified by flash chromatography (silica-gel, petroleum ether/EtOAc 200:1) to afford the product as a clear oil (4.6 g, 81%). 1H NMR (300 MHz, CDCl3) δ 7.13-7.22 (m, 5H), 6.34 (s, 2H), 3.76 (s, 6H), 2.60-2.64 (m, 4H), 2.31 (s, 3H), 1.53-1.67 (m, 4H).
Reaction SMILES: C[O:2][C:3](=[O:36])[CH2:4][O:5][C:6]1[CH:35]=[CH:34][C:9]2[C:10](=[O:33])[CH2:11][C:12]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:25]=[CH:24][C:23]([C:26](=[O:28])[CH3:27])=[C:22]([OH:29])[C:21]=3[CH2:30][CH2:31][CH3:32])([CH3:14])[O:13][C:8]=2[CH:7]=1.[OH-].[Li+]>O1CCCC1.O>[C:26]([C:23]1[CH:24]=[CH:25][C:20]([O:19][CH2:18][CH2:17][CH2:16][CH2:15][C:12]2([CH3:14])[CH2:11][C:10](=[O:33])[C:9]3[CH:34]=[CH:35][C:6]([O:5][CH2:4][C:3]([OH:36])=[O:2])=[CH:7][C:8]=3[O:13]2)=[C:21]([CH2:30][CH2:31][CH3:32])[C:22]=1[OH:29])(=[O:28])[CH3:27]
Reactant: CCCc1c(OCCCCC2(C)CC(=O)c3ccc(OCC(=O)OC)cc3O2)ccc(C(C)=O)c1O
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CCCc1c(OCCCCC2(C)CC(=O)c3ccc(OCC(=O)O)cc3O2)ccc(C(C)=O)c1O
Yield: 97.9 %

Procedure:
Using the procedure of Example 24, the chromanone ester from Example 39 was saponified with lithium hydroxide in tetrahydrofuran-water giving rac.-[[2-[4-(4-acetyl-3-hydroxy-2-propylphenoxy)butyl]-3,4-dihydro-2-methyl-4-oxo-2H-1-benzopyran-7-yl]oxy]acetic acid in 97.9% yield, as a viscous, amber oil.
Reaction SMILES: C1N2CN3CN(C2)CN1C3.[CH3:11][O:12][C:13]1[CH:30]=[CH:29][C:16]([CH2:17][N:18]2[C:22](=[O:23])[C:21]3=[CH:24][CH:25]=[CH:26][CH:27]=[C:20]3[C:19]2=[O:28])=[CH:15][CH:14]=1.FC(F)(F)[C:33](O)=[O:34].C(=O)([O-])[O-].[K+].[K+]>O>[CH:33]([C:30]1[CH:29]=[C:16]([CH:15]=[CH:14][C:13]=1[O:12][CH3:11])[CH2:17][N:18]1[C:22](=[O:23])[C:21]2=[CH:24][CH:25]=[CH:26][CH:27]=[C:20]2[C:19]1=[O:28])=[O:34]
Reactant: COc1ccc(CN2C(=O)c3ccccc3C2=O)cc1
Reactant: O=C(O)C(F)(F)F
Agent: C1N2CN3CN1CN(C2)C3
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: COc1ccc(CN2C(=O)c3ccccc3C2=O)cc1C=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
18 g of hexamethylene tetramine was added little by little to a mixture of 31 g N-(4-methoxybenzyl)phthalimide and 100 ml trifluoroacetic acid, stirred at room temperature for 1 hr, and then heated under reflux for 4 hr. The reaction solution was cooled to 1° C., and water was added thereto. Potassium carbonate was added thereto and the resulting crystals were collected by filtration. The crystals were dried to give 20 g of N-(3-formyl-4-methoxybenzyl)phthalimide.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]1[CH2:11][CH:10]=1.C(N(CC)CC)C.[CH3:19][S:20](Cl)(=[O:22])=[O:21]>CCOCC>[CH3:19][S:20]([O:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]1[CH2:11][CH:10]=1)(=[O:22])=[O:21]
Reactant: CS(=O)(=O)Cl
Reactant: OCCCCCCCC1=CC1
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCCCCCCCC1=CC1
Temperature: 0 °C

Procedure:
A solution of 3.8 mmol of 1-(7-hydroxyheptyl)-cyclopropene in 50 ml of ether was cooled in an ice bath. Triethylamine (1 ml) and 0.48 g of methanesulfonyl chloride (4.2 mmol) were added and the reaction mixture was stirred for 2½ hours at 0° C. The reaction mixture was washed with water and brine, dried over magnesium sulfate, filtered and stripped to give 1-(7-methanesulfonyloxyheptyl)-cyclopropene which was used without further purification.
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:13][CH2:12][C@H:11]([CH2:14]Br)[CH2:10][CH2:9]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[C:16]1([CH:23]=[CH:22][C:20]([OH:21])=[CH:19][CH:18]=1)[OH:17].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:1]([C@H:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][O:17][C:16]2[CH:23]=[CH:22][C:20]([OH:21])=[CH:19][CH:18]=2)[CH2:10][CH2:9]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: Oc1ccc(O)cc1
Reactant: CCCCCCC[C@H]1CC[C@H](CBr)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCCCC[C@H]1CC[C@H](COc2ccc(O)cc2)CC1
Temperature: 0 °C

Procedure:
A mixture of 5.0 g of (trans-4-heptylcyclohexyl)methyl bromide, 10.0 g of hydroquinone, 10.0 g of anhydrous potassium carbonate and 100 ml of absolute dimethylformamide was heated under reflux overnight. The cooled reaction mixture was subsequently poured into ice-water and extracted three times with 50 ml of diethyl ether each time. The organic phases were washed with 500 ml of water, dried over magnesium sulphate and concentrated. Chromatography of the residue on silica gel with toluene/ethyl acetate (vol. 4:1) gave 1.8 g of 4-[(trans-4-heptylcyclohexyl)methoxy]phenol; m.p. 107°-108° C.
Reaction SMILES: C=[C:2]1[CH2:5][N:4]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:3]1=[O:12].[O:13]=[O+][O-].O=O.CSC>C(OCC)(=O)C.O>[C:6]1([N:4]2[CH2:5][C:2](=[O:13])[C:3]2=[O:12])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: C=C1CN(c2ccccc2)C1=O
Reactant: O=[O+][O-]
Agent: O=O
Solvent: CSC
Solvent: CCOC(C)=O
Solvent: O
Product: O=C1CN(c2ccccc2)C1=O
Temperature: -70 °C
Reaction time: 1.5 h

Procedure:
800 mg (5 mmol) methylene-1-phenyl-azetidine-2-one were dissolved in 50 ml of ethyl acetate and cooled to -70° C. For 15 min ozone was passed through the solution and then oxygen for 1 hour. Then 0.5 ml dimethylsulfide were added, and the solution was stirred for 1.5 hour at -70° C. The temperature was raised to 0° C., and 25 ml of water were added. After 5 min the organic phase was separated and extracted with each of 50 ml of sodium thiosulfate solution and 50 ml of ferrous sulfate solution and then dried over magnesium sulfate. The solvent was evaporated and the residue purified by chromatography over silica gel (eluent: benzene). Yield: 114 mg (14.5%) M.p. 115°-117° C. IR(KBr): 1822, 1757 cm-1
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6](Cl)=[O:7].[CH2:12]([NH:19][C:20]([C:22]1[S:26][C:25]([NH2:27])=[N:24][C:23]=1[CH3:28])=[O:21])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>>[CH2:12]([NH:19][C:20]([C:22]1[S:26][C:25]([NH:27][C:6](=[O:7])[C:5]2[CH:9]=[CH:10][CH:11]=[C:3]([O:2][CH3:1])[CH:4]=2)=[N:24][C:23]=1[CH3:28])=[O:21])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Cc1nc(N)sc1C(=O)NCc1ccccc1
Reactant: COc1cccc(C(=O)Cl)c1
Product: COc1cccc(C(=O)Nc2nc(C)c(C(=O)NCc3ccccc3)s2)c1
Yield: 34 %

Procedure:
Following the procedure as described in Example 2, making variations only as required to use 3-methoxybenzoyl chloride in place of benzoyl chloride to react with 2-amino-4-methylthiazole-5-carboxylic acid benzylamide, the title compound was obtained as a white solid in 34% yield; m.p. 75-77° C.; 1H NMR (CDCl3, 300 MHz) δ 7.43-7.31 (m, 8H), 7.12 (td, J=2.4, 6.7 Hz, 1H), 5.97 (t, J=5.6 Hz, 1H), 4.58 (d, J=5.6 Hz, 2H), 3.82 (s, 3H), 2.47 (s, 3H); MS (ES+) m/z 382.1 (M+1).