Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([OH:13])[C:11]=1[OH:12])[C:5]([O:7]C)=[O:6].C([O-])([O-])=O.[K+].[K+].Br[CH2:21][CH3:22].[CH3:23][C:24](C)=O>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:13][CH2:21][CH3:22])[C:11]=1[O:12][CH2:23][CH3:24])[C:5]([OH:7])=[O:6]
Reactant: COC(=O)c1cc(O)c(O)c(Cl)c1
Reactant: CC(C)=O
Reactant: CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CCOc1cc(C(=O)O)cc(Cl)c1OCC
Temperature: 60 °C
Reaction time: 18 h

Procedure:
To a solution of methyl 3-chloro-4,5-dihydroxybenzoate (D68) (1.0 g) in acetone (50 mL) stirred at room temp was added K2CO3 (6.9 g) and bromoethane (5.5 g). The reaction mixture was stirred at 60° C. for 18 h. After filteration, the filtrate was concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (20 mL) and methanol (20 mL), a solution of NaOH (1.0 g) in water (20 mL) was added to the above solution. The resulted mixture was stirred for 4 h and then the organic solvent was removed in vacuo. The aqueous layer was acidified with concentrated HCl to pH around 1. The solid was filtered and dried in vacuo to afford 3-chloro-4,5-bis(ethyloxy)benzoic acid (D69) (769 mg). δH (DMSO-d6, 400 MHz): 1.29 (3H, t), 1.36 (3H, t), 4.08-4.15 (4H, m), 7.46 (1H, d), 7.53 (1H, d), 13.16 (1H, br s). MS (ES): C11H13ClO4 requires 244; found 245.1 (M+H+).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[Cl:11][C:12]1[CH:13]=[C:14]([S:19](Cl)(=[O:21])=[O:20])[CH:15]=[C:16]([Cl:18])[CH:17]=1.O.C(OCC)(=O)C>N1C=CC=CC=1>[Cl:18][C:16]1[CH:15]=[C:14]([S:19]([NH:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[CH:5]3)(=[O:20])=[O:21])[CH:13]=[C:12]([Cl:11])[CH:17]=1
Reactant: Nc1ccc2[nH]ccc2c1
Reactant: O=S(=O)(Cl)c1cc(Cl)cc(Cl)c1
Solvent: c1ccncc1
Solvent: O
Solvent: CCOC(C)=O
Product: O=S(=O)(Nc1ccc2[nH]ccc2c1)c1cc(Cl)cc(Cl)c1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
100 mg 5-aminoindole are dissolved in 10 ml of pyridine. 186 mg 3,5-dichlorophenylsulphonyl chloride are added thereto and the mixture is stirred for 4 hours at ambient temperature. The solvent is eliminated in vacuo and the residue is divided between water and ethyl acetate. The aqueous phase is extracted with ethyl acetate and the combined organic phases are washed with saturated sodium chloride solution. After drying with magnesium sulphate the solvents are eliminated in vacuo and the residue is chromatographed on silica gel (cyclohexane/ethyl acetate 10:1 to 1:5).
Reaction SMILES: [CH2:1]([C:3]1([CH2:15][CH3:16])[O:8][C:7](=[O:9])[NH:6][C:5]2[CH:10]=[CH:11][C:12](I)=[CH:13][C:4]1=2)[CH3:2].[Cl:17][C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[CH:22][CH:23]=1>>[Cl:17][C:18]1[CH:23]=[C:22]([N:6]2[C:5]3[CH:10]=[CH:11][CH:12]=[CH:13][C:4]=3[C:3]([CH2:15][CH3:16])([CH2:1][CH3:2])[O:8][C:7]2=[O:9])[CH:21]=[CH:20][CH:19]=1
Reactant: OB(O)c1cccc(Cl)c1
Reactant: CCC1(CC)OC(=O)Nc2ccc(I)cc21
Product: CCC1(CC)OC(=O)N(c2cccc(Cl)c2)c2ccccc21

Procedure:
Prepared from 4,4-diethyl-6-iodo-1,4-dihydrobenzo[d][1,3]oxazin-2-one and 3-chlorophenyl boronic acid according to Procedure A. White solid: mp 150-151° C. 1H-NMR (CDCl3) δ8.52 (s, 1H, D2O exchangeable), 7.50 (s, 1H), 7.31-7.44 (m, 4H), 7.16 (d, 1H, J=1.5 Hz), 6.89 (d, 1H, J=8.2 Hz), 2.03 (m, 4H), 0.94 (t, 6H, J=7.4 Hz); MS (EI) m/z 315(M+, 53%). Anal. Calc. For C18H18ClNO2: C, 68.46, H, 5.75, N, 4,44. Found: C, 68.16, H, 5.81, N, 4.32.
Reaction SMILES: [C:1]1([N:7]([CH2:40][CH2:41][CH2:42][O:43]CC2C=CC=CC=2)[C:8]([C:10]2[CH:39]=[CH:38][C:13]3[N:14]([CH3:37])[C:15]([CH2:17][NH:18][C:19]4[CH:24]=[CH:23][C:22]([C:25](=[NH:36])[NH:26][C:27]([O:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])=[O:28])=[CH:21][CH:20]=4)=[N:16][C:12]=3[CH:11]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>ClCCl.C(O)C>[C:1]1([N:7]([CH2:40][CH2:41][CH2:42][OH:43])[C:8]([C:10]2[CH:39]=[CH:38][C:13]3[N:14]([CH3:37])[C:15]([CH2:17][NH:18][C:19]4[CH:24]=[CH:23][C:22]([C:25](=[NH:36])[NH:26][C:27]([O:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])=[O:28])=[CH:21][CH:20]=4)=[N:16][C:12]=3[CH:11]=2)=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCCCCCOC(=O)NC(=N)c1ccc(NCc2nc3cc(C(=O)N(CCCOCc4ccccc4)c4ccccc4)ccc3n2C)cc1
Solvent: ClCCl
Solvent: CCO
Product: CCCCCCOC(=O)NC(=N)c1ccc(NCc2nc3cc(C(=O)N(CCCO)c4ccccc4)ccc3n2C)cc1
Yield: 26 %

Procedure:
Prepared analogously to Example 165 from 1-methyl-2-[N-[4-(N-n-hexyloxycarbonylamidino)phenyl]aminomethyl]benzimidazol-5-yl-carboxylic acid-N-phenyl-N-(3-benzyloxy-n-propyl)amide by catalytic debenzylation. Yield: 26% of theory, C33H40N6O4 (584.7); Rf value: 0.39 (silica gel; dichloromethane/ethanol=9:1); EKA mass spectrum: (M+H)+=585; (M+H+Na)++=304; (M+Na)+=607.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[CH2:7][CH2:6]1.[CH:19]1([N:25]=[C:26]=[O:27])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1>O1CCCC1>[Cl:18][C:15]1[CH:14]=[CH:13][C:12]([CH2:11][N:8]2[CH2:9][CH2:10][N:5]([CH2:4][CH2:3][CH2:2][NH:1][C:26]([NH:25][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)=[O:27])[CH2:6][CH2:7]2)=[CH:17][CH:16]=1
Reactant: NCCCN1CCN(Cc2ccc(Cl)cc2)CC1
Reactant: O=C=NC1CCCCC1
Solvent: C1CCOC1
Product: O=C(NCCCN1CCN(Cc2ccc(Cl)cc2)CC1)NC1CCCCC1
Yield: 55 %

Procedure:
A solution of 1-(3-aminopropyl)-4-(4-chlorobenzyl)-piperazine (2.0 g; 7.5 mmole) and cyclohexyl isocyanate (1.6 g; 12.8 mmole) in tetrahydrofuran (5 ml) was stirred at room temperature for 30 minutes. The reaction mixture was evaporated under reduced pressure, and the residual oil was dissolved in ethanol (10 ml). The crude product was precipitated as a white solid by the addition of water, collected at filtration and recrystallized twice from cyclohexane to yield 1-{3-[4-(4-chlorobenzyl)piperazin-1-yl]-propyl}-3-cyclohexylurea (1.62 g; 56% yield) as a white crystalline solid, m.p. 109°-112° C. This product in methylene chloride (20 ml) was precipitated as the dihydrochloride by the addition of excess anhydrous hydrogen chloride. Recrystallization from water provided the title compound as colorless crystals, m.p. 184°-187° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[NH:5][C:6]1[C:7]2[CH:15]=[CH:14][C:13](F)=[N:12][C:8]=2[N:9]=[CH:10][N:11]=1.[CH3:20][O-:21].[Na+].O>CO>[Br:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[NH:5][C:6]1[C:7]2[CH:15]=[CH:14][C:13]([O:21][CH3:20])=[N:12][C:8]=2[N:9]=[CH:10][N:11]=1
Reactant: C[O-]
Reactant: Fc1ccc2c(Nc3cccc(Br)c3)ncnc2n1
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COc1ccc2c(Nc3cccc(Br)c3)ncnc2n1
Yield: 85.7 %

Procedure:
A solution of 4-(3-bromoanilino)-7-fluoropyrido[2,3-d]pyrimidine (0.26 g, 0.81 mmol) and sodium methoxide (prepared from 75 mg of sodium, 3.26 mmol) in dry MeOH (15 mL) is heated at 90° C. in a pressure vessel for 18 h. The mixture is poured into water and extracted with EtOAc to give 4-(3-bromoanilino)-7-methoxypyrido[2,3-d]pyrimidine (0.23 g, 86%). 1H NMR (DMSO) δ 9.88 (1H, brs), 8.82 (1H, d, J=8.9 Hz), 8.71 (1H, s), 8.18 (1H, dd, J=8.0, 1,9 Hz), 7.36 (1H, dd, J=8.1, 8.0 Hz), 7.29 (1H, ddd, J=8.1, 1.9, 1,9 Hz) 7.15 (1H, d, J=8.9 Hz), 4.01 (3H, s).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([CH2:20][C:21]([OH:24])([CH3:23])[CH3:22])[N:15]=[CH:14]3)=[C:6]([CH:9]=1)[C:7]#[N:8].N1C(C)=CC=CC=1C.[Si:33](OS(C(F)(F)F)(=O)=O)([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34]>ClCCl.CCOCC>[Si:33]([O:24][C:21]([CH3:22])([CH3:23])[CH2:20][N:16]1[C:17]2[C:13](=[CH:12][C:11]([O:10][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:9][C:6]=3[C:7]#[N:8])=[CH:19][CH:18]=2)[CH:14]=[N:15]1)([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34]
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Reactant: CC(C)(O)Cn1ncc2cc(Oc3ccc(F)cc3C#N)ccc21
Solvent: ClCCl
Solvent: CCOCC
Solvent: Cc1cccc(C)n1
Product: CC(C)(Cn1ncc2cc(Oc3ccc(F)cc3C#N)ccc21)O[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 75.1 %

Procedure:
To a cooled (0° C.) solution of 5-Fluoro-2-[1-(2-hydroxy-2-methylpropyl)-1H-indazol-5-yloxy]-benzonitrile (0.070 g, 0.215 mmol) and 2,6-lutidine (0.030 g, 0.284 mmol) in dichloromethane (2 mL) was added TBSOTf (0.063 g, 0.240 mmol). The reaction mixture was warmed to room temperature and stirred for 1 hour. The mixture was diluted with ether (50 mL) and washed with 0.2N HCl, NaHCO3, and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was chromatographed eluting with ether/hexanes (1:3) to afford 0.071 g of pale yellow oil (94% yield).
Reaction SMILES: [CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]([C:11]1[S:15][C:14]([C:16](=[O:21])[C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=1)#[CH:10].[N-:22]=[N+:23]=[N-:24].[Na+].CC(O)(C)C>O.[O-]S([O-])(=O)=O.[Cu+2]>[CH2:1]([N:22]1[CH:10]=[C:9]([C:11]2[S:15][C:14]([C:16](=[O:21])[C:17]([F:19])([F:18])[F:20])=[CH:13][CH:12]=2)[N:24]=[N:23]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C#Cc1ccc(C(=O)C(F)(F)F)s1
Reactant: [N-]=[N+]=[N-]
Reactant: BrCc1ccccc1
Agent: [Cu+2]
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)(C)O
Product: O=C(c1ccc(-c2cn(Cc3ccccc3)nn2)s1)C(F)(F)F
Temperature: 50 °C

Procedure:
Benzyl bromide (1.0 eq), D2 (1.05 eq) and NaN3 (1.05 eq) were suspended in a 1:1 mixture of H2O and t-BuOH (0.1M) in a 10-mL glass vial equipped with a small magnetic stirring bar. To this was added Cu powder (0.8 eq) and CuSO4 solution (1.0M, 0.2 eq) and the vial was tightly sealed with an aluminum/Teflon crimp top. The mixture was then irradiated for 10 min at 125° C., using an irradiation power of 100 W. After completion of the reaction, the vial was cooled to 50° C. with air jet cooling before it was opened. It was then diluted with H2O and precipitated product was collected by filtration, and washed with cold H2O, followed by 0.25M HCl and finally with Petroleum ether to furnish a crude material which was purified by preparative RP-HPLC, using H2O (+0.1% TFA) and MeCN (+0.1% TFA) as eluents (column: C18) and the desired fractions were freeze dried to yield the product (D3). 1H NMR (400 MHz, DMSO, 300). δ 8.92 (1H, s), 8.16-8.12 (1H, m), 7.73 (1H, d, J=4.4 Hz), 7.44-7.33 (5H, m), 5.70 (2H, s). MS (ES) C15H10F3N3OS requires: 337, found: 338 (M+H+) and 356 (M+H2O+H)+.
Reaction SMILES: C(OC([N:8]=[S:9]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])([CH3:11])=[O:10])=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH2:16]([O:15][C:13](=[O:14])[CH2:12][S:9]([CH3:11])(=[NH:8])=[O:10])[CH3:17]
Reactant: CCOC(=O)CS(C)(=O)=NC(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)CS(C)(=N)=O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of ethyl [N-(tert-butoxycarbonyl)-S-methylsulfonimidoyl]acetate in dichloromethane (2.5 mL) was cooled to 0° C. followed by a dropwise addition of trifluoroacetic acid (0.79 mL). The reaction was then stirred at RT for 2 hours. The excess TFA was removed under reduced pressure and the oily residue was partitioned between EtOAc and saturated aq NaHCO3/brine. The organic layer was separated, washed with brine (1×), and dried over Na2SO4. The upper solution layer was decanted and concentrated yielding the title compound as a brown oil (49 mg).
Reaction SMILES: [CH:1](=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[OH2:8]>>[CH2:1]([OH:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[C:1]([OH:8])(=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCCC=O
Reactant: O
Product: CCCCCC(=O)O
Product: CCCCCCO

Procedure:
Many aldehydes form an azeotrope with water. For example, hexanal and water form an azeotrope that boils at 91° C. Hexanol and hexanoic acid likewise form azeotropes with water, which boil at 97.8° C. and 99.9° C., respectively. Despite the fact that the boiling points are close together, the distillation process is surprisingly free of problems. Pure fractions of alcohol and aldehyde can be collected.
Reaction SMILES: [CH3:1][N:2]1[C:6]([C:7]2[CH:8]=[CH:9][C:10]3[NH:19][C:18](=O)[O:17][C:13]4([CH2:16][CH2:15][CH2:14]4)[C:11]=3[CH:12]=2)=[CH:5][CH:4]=[C:3]1[C:21]#[N:22].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:32])=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1>[CH3:1][N:2]1[C:6]([C:7]2[CH:8]=[CH:9][C:10]3[NH:19][C:18](=[S:32])[O:17][C:13]4([CH2:16][CH2:15][CH2:14]4)[C:11]=3[CH:12]=2)=[CH:5][CH:4]=[C:3]1[C:21]#[N:22]
Reactant: Cn1c(C#N)ccc1-c1ccc2c(c1)C1(CCC1)OC(=O)N2
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: Cn1c(C#N)ccc1-c1ccc2c(c1)C1(CCC1)OC(=S)N2
Yield: 99.9 %

Procedure:
A solution of 1-methyl-5-(2-oxo-1,2-dihydrospiro [3,1-benzoxazine-4,1′-cyclobutan]-6-yl)-1H-pyrrole-2-carbonitrile (0.33 g, 1.1 mmol) and Lawesson's Reagent (0.23 g, 0.55 mmol) in toluene (10 mL) was heated at 100° C. Upon completion by TLC, the reaction mixture was poured into saturated sodium carbonate (100 mL) and extracted with ethyl acetate (50 mL), dried over magnesium sulfate, and concentrated. Trituration of the residue with ether (20 mL) gave 1-methyl-5-(2-thioxo-1,2-dihydrospiro[3,1-benzoxazine-4,1′-cyclobutan]-6-yl)-1H-pyrrole-2-carbonitrile (0.17 g, 49%) as a tan solid. 1H NMR (DMSO-d6): δ 12.35 (s, 1H), 7.64 (d, 1H, J=2.0 Hz), 7.51 (dd, 1H, J=8.2, 2.0 Hz), 7.15 (d, 1H, J=8.3 Hz), 7.05 (d, 1H, J=4.03 Hz), 6.43 (d, 1H, J=4.03 Hz), 3.73 (s, 3H), 2.59-2.53 (m, 2H), 2.09-2.02 (m, 2H), 1.93-1.85 (m, 2H). MS (ESI) m/z 310 ([M+H]+); MS (ESI) m/z 308 ([M−H]−); HRMS: calcd for C17H15N3OS, 309.0936; found (ESI_FT), 310.10057.
Reaction SMILES: CC1C=CC(S(O[CH2:12][C:13]([C:16]#[N:17])([CH3:15])[CH3:14])(=O)=O)=CC=1.[Br:18][C:19]1[C:24]([CH3:25])=[CH:23][C:22]([OH:26])=[CH:21][C:20]=1[CH3:27].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C)C=O.C(OCC)C>[Br:18][C:19]1[C:24]([CH3:25])=[CH:23][C:22]([O:26][CH2:12][C:13]([CH3:15])([CH3:14])[C:16]#[N:17])=[CH:21][C:20]=1[CH3:27]
Reactant: Cc1cc(O)cc(C)c1Br
Reactant: Cc1ccc(S(=O)(=O)OCC(C)(C)C#N)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOCC
Solvent: CN(C)C=O
Product: Cc1cc(OCC(C)(C)C#N)cc(C)c1Br
Temperature: 80 °C
Reaction time: 12 h

Procedure:
To a solution of 2-cyano-2-methylpropyl 4-methylbenzenesulfonate (760 mg) and 4-bromo-3,5-dimethylphenol (500 mg) in N,N-dimethylformamide (8 mL) is added Cs2CO3 (2.0 g). The mixture is stirred for 12 hours at 80° C., diluted with diethylether and washed with water and brine. After drying (MgSO4) the solvent is evaporated and the residue is chromatographed on silica gel (petrole ether/ethyl acetate 90:10→60:40) to give the title compound. Yield: 572 mg; Mass spectrum (ESI+): m/z=282 [M+H]+.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][SH:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.F[C:12]1[CH:17]=[CH:16][C:15]([C:18](=[O:20])[CH3:19])=[CH:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[C:1]1([CH2:7][CH2:8][CH2:9][S:10][C:12]2[CH:17]=[CH:16][C:15]([C:18](=[O:20])[CH3:19])=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(=O)c1ccc(F)cc1
Reactant: SCCCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)c1ccc(SCCCc2ccccc2)cc1

Procedure:
A mixture of 174.6 grams (1.15 mole) of 3-phenylpropyl thiol, 158.8 grams (1.15 mole) of p-fluoroacetophenone and 158.8 grams (1.15 mole) of potassium carbonate in 500 ml. of dry dimethylformamide is stirred at its reflux temperature for approximately 24 hours. The reaction mixture is cooled, water added and extracted with methylene chloride. The extract is washed with water, a solution of 2 N sodium hydroxide, dried over anhydrous sodium sulfate and evaporated in vacuo. The residue is recrystallized from isopropyl alcohol to yield the desired p-(3-phenylpropylthio)acetophenone having a m.p. of 76°-8° C.
Reaction SMILES: Cl[CH2:2][C@H:3]1[O:8][C:7]([CH3:10])([CH3:9])[O:6][C@@H:5]([CH2:11][C:12]([OH:14])=[O:13])[CH2:4]1.CC(Cl)(C)C.[Cl-].CN1CCCC1=[O:27]>C([O-])(=O)C.C([N+](CCCC)(CCCC)CCCC)CCC>[OH:27][CH2:2][C@H:3]1[O:8][C:7]([CH3:10])([CH3:9])[O:6][C@@H:5]([CH2:11][C:12]([OH:14])=[O:13])[CH2:4]1
Reactant: CN1CCCC1=O
Reactant: CC1(C)O[C@H](CCl)C[C@H](CC(=O)O)O1
Agent: CC(=O)[O-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Solvent: CC(C)(C)Cl
Product: CC1(C)O[C@H](CO)C[C@H](CC(=O)O)O1
Temperature: 85 °C
Reaction time: 0.75 h

Procedure:
Solid tetrabutylammonium acetate obtained as above (111 g, 0.368 mole) was added in one portion to a mechanically stirred solution of the chloride (4R-cis)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid, 1,1-dimethylethyl ester prepared in step (d) above (35 g, 0.125 mole) in HPLC grade 1-methyl-2-pyrrolidinone (504 ml) under argon. The resulting solution was stirred at 85° C. (internal temperature). After 30 to 60 minutes the reaction mixture became homogeneous and brown in color. The progress of the reaction was followed by TLC and GC analysis. (TLC: Rf=0.63 for the chloride starting material; Rf =0.54 for the title compound (silica gel, Ethyl acetate:Hexane, 1:1, visualization by Ce(SO4)2 spray). GC: Rt =7.20 minutes (starting material) and 8.66 minutes (title compound).) After 11 hours the reaction was completed.
Reaction SMILES: [CH:1]1[C:14]2[C:13](=[O:15])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6](=[O:16])[C:5]=2[CH:4]=[CH:3][CH:2]=1.[N+:17]([O-])([OH:19])=[O:18].S(=O)(=O)(O)O>C(Cl)Cl>[N+:17]([C:8]1[C:7]2[C:6](=[O:16])[C:5]3[C:14](=[CH:1][CH:2]=[CH:3][CH:4]=3)[C:13](=[O:15])[C:12]=2[CH:11]=[CH:10][CH:9]=1)([O-:19])=[O:18]
Reactant: O=C1c2ccccc2C(=O)c2ccccc21
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Solvent: ClCCl
Product: O=C1c2ccccc2C(=O)c2c1cccc2[N+](=O)[O-]
Temperature: 20 °C
Reaction time: 4 h

Procedure:
A suspension of 250 g. of anthraquinone in 200 ml. of methylene chloride is treated under reflux conditions, over the course of about 3 hours, with a nitration acid of 68.4 ml. of 98% strength nitric acid and 85.2 ml. of 100% strength sulphuric acid. The mixture is stirred for a further 4 hours at this temperature and cooled to 20°C. After 700 ml. of methylene chloride have been added, 190 ml. of 98% strength nitric acid are allowed to run in at 20°C. After stirring for about 30 minutes longer, the upper, organic phase is withdrawn and clarified by passing it through a frit, and the filter residue is rinsed with a mixture of 95 ml. of methylene chloride and 5 ml. of 98% strength nitric acid. The clear filtrate is decomposed with 500 ml. of water and the mixture is stirred for a further hour at about 20°C. The lemon-yellow precipitate is then filtered off and is washed successively with 2 × 100 ml. of methylene chloride and 2 × 100 ml. of 1% strength aqueous di-sec.-butylnaphthalene-sulphonate solution and finally with water until neutral. After drying at about 100°C, the yield is 229 g. The product contains 89% of 1-nitroanthraquinone and inter alia contains 0.25% of anthraquinone, <0.25% of 2-nitroanthraquinone and 1.4% of 1,5-dinitroanthraquinone. To remove the remaining subsidiary components, the 1-nitroanthraquinone obtained is stirred with 1,850 ml. of 2.5% strength sodium sulphite solution for 4 hours under reflux conditions, then filtered off hot, washed and dried. 204 g. of 1-nitroanthraquinone are obtained, containing 95% of 1-nitroanthraquinone, 0.25% of anthraquinone, <0.25% of 2-nitroanthraquinone and 0.9% of 1,5-dinitroanthraquinone. A further fraction of 12 g. of 1-nitroanthraquinone and 2 g. of anthraquinone remains in the methylene chloride mother liquor and can, after evaporation of the solvent, be reintroduced into the next nitration batch.
Reaction SMILES: [CH2:1]([C:3]1[O:4][C:5]2[C:15]([N:16]=1)=[CH:14][C:8]1[CH2:9][CH2:10][NH:11][CH2:12][CH2:13][C:7]=1[CH:6]=2)[CH3:2].[Cl:17][CH2:18][CH2:19][CH2:20][S:21][C:22]1[N:26]([CH3:27])[C:25]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[C:30]([F:35])[CH:29]=2)=[N:24][N:23]=1>>[ClH:17].[F:35][C:30]1[CH:29]=[C:28]([C:25]2[N:26]([CH3:27])[C:22]([S:21][CH2:20][CH2:19][CH2:18][N:11]3[CH2:10][CH2:9][C:8]4[CH:14]=[C:15]5[N:16]=[C:3]([CH2:1][CH3:2])[O:4][C:5]5=[CH:6][C:7]=4[CH2:13][CH2:12]3)=[N:23][N:24]=2)[CH:33]=[CH:32][C:31]=1[F:34]
Reactant: CCc1nc2cc3c(cc2o1)CCNCC3
Reactant: Cn1c(SCCCCl)nnc1-c1ccc(F)c(F)c1
Product: CCc1nc2cc3c(cc2o1)CCN(CCCSc1nnc(-c2ccc(F)c(F)c2)n1C)CC3
Product: Cl

Procedure:
The title compound was prepared in analogy to General Procedure 1 from 2-ethyl-6,7,8,9-tetrahydro-5H-[1,3]oxazolo[4,5-h][3]benzazepine (0.25 mmol) and 3-[(3-chloropropyl)thio]-5-(3,4-difluorophenyl)-4-methyl-4H-1,2,4-triazole and was obtained as a faint yellow slightly hygroscopic solid (0.11 mmol).
Reaction SMILES: [CH2:1]([O:19][CH2:20][CH:21]([CH2:41][OH:42])[O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]/[CH:31]=[CH:32]\[CH2:33]/[CH:34]=[CH:35]\[CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11]/[CH:12]=[CH:13]\[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].C(N(CC)CC)C.[S:50](Cl)([CH3:53])(=[O:52])=[O:51]>>[CH2:1]([O:19][CH2:20][CH:21]([CH2:41][O:42][S:50]([CH3:53])(=[O:52])=[O:51])[O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]/[CH:31]=[CH:32]\[CH2:33]/[CH:34]=[CH:35]\[CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11]/[CH:12]=[CH:13]\[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CS(=O)(=O)Cl
Reactant: CCCCC/C=C\C/C=C\CCCCCCCCOCC(CO)OCCCCCCCC/C=C\C/C=C\CCCCC
Solvent: CCN(CC)CC
Product: CCCCC/C=C\C/C=C\CCCCCCCCOCC(COS(C)(=O)=O)OCCCCCCCC/C=C\C/C=C\CCCCC
Temperature: -15 °C
Reaction time: 1 h

Procedure:
1,2-Dilinoleylglycerol (26) (11.0 g, 18.7 mmol), triethylamine (5.04 mL, 36 mmol), and a stir bar were added to a 250 mL round bottom flask. The flask was sealed and flushed with nitrogen. Anhydrous DCM (75 mL) was added, and the mixture cooled to −15° C. (Ice and NaCl). Mesyl Chloride (2.80 mL, 36 mmol) was added via syringe over a 5 minute period, and the reaction stirred at −15° C. for 1 hour. At this point TLC showed that the starting material had been consumed. The solution was diluted with DCM (120 mL) and washed with saturated NaHCO3 (2×150 mL). The organic phase was then dried (MgSO4), filtered, concentrated, and the product purified by column chromatography (10.6 g, 85%).
Reaction SMILES: Cl[C:2]1[C:3]2[CH2:17][CH2:16][CH2:15][C:4]=2[N:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[CH:9]=2)[N:7]=1.[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][S:26]([NH2:29])(=[O:28])=[O:27])=[CH:21][CH:20]=1>>[Cl:14][C:10]1[CH:9]=[C:8]([C:6]2[N:7]=[C:2]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([CH2:25][S:26]([NH2:29])(=[O:27])=[O:28])=[CH:21][CH:20]=3)[C:3]3[CH2:17][CH2:16][CH2:15][C:4]=3[N:5]=2)[CH:13]=[CH:12][CH:11]=1
Reactant: Nc1ccc(CS(N)(=O)=O)cc1
Reactant: Clc1cccc(-c2nc(Cl)c3c(n2)CCC3)c1
Product: NS(=O)(=O)Cc1ccc(Nc2nc(-c3cccc(Cl)c3)nc3c2CCC3)cc1
Yield: 37 %

Procedure:
Following General Procedure A1, 4-chloro-2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (0.075 g, 0.28 mmol) was reacted with (4-aminophenyl)methanesulfonamide (0.058 g, 0.31 mmol) to afford the title compound (0.043 g, 58%) as a white solid. MW=414.91. 1H NMR (DMSO-d6, 300 MHz) δ 8.93 (s, 1H), 8.32-8.21 (m, 2H), 7.85 (d, J=8.6 Hz, 2H), 7.57-7.50 (m, 2H), 7.36 (d, J=8.6 Hz, 2H), 6.85 (s, 2H), 4.25 (s, 2H), 2.99-2.86 (m, 4H), 2.18-2.05 (m, 2H); APCI MS m/z 415 [M+H]+.