Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][N:3]=1.[CH2:9]([O:11][CH2:12]Cl)[CH3:10].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([O:8][CH2:12][O:11][CH2:9][CH3:10])=[CH:4][N:3]=1
Reactant: CCOCCl
Reactant: Oc1cnc(Cl)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOCOc1cnc(Cl)nc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 87.9 %

Procedure:
A stirred mixture of 2-chloro-5-pyrimidinol (107) (1.00 g, 7.66 mmol) and chloromethyl ethyl ether (1.75 mL, 18.9 mmol) in anhydrous DMF (2.5 mL) was treated with K2CO3 (2.15 g, 15.6 mmol). After stirring at room temperature for 16 h, the mixture was added to ice/aqueous NaHCO3 (100 mL) and extracted with 50% Et2O/petroleum ether (5×100 mL). The combined extracts were evaporated to dryness and the residue was chromatographed on silica gel. Elution with 0-1% Et2O/petroleum ether firstly gave foreruns, and then further elution with 1-10% Et2O/petroleum ether gave 2-chloro-5-(ethoxymethoxy)pyrimidine (108) (1.27 g, 88%) as an oil; 1H NMR (CDCl3) δ 8.43 (s, 2H), 5.27 (s, 2H), 3.74 (q, J=7.1 Hz, 2H), 1.23 (t, J=7.1 Hz, 3 H); HRESIMS calcd for C7H10ClN2O2 m/z [M+H]+ 191.0396, 189.0425. found 191.0397, 189.0426.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([C:19](Cl)=[O:20])[CH:13]=2)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH3:22][NH:23][CH3:24]>C(Cl)Cl.O>[Cl:1][C:2]1[C:3]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([C:19]([N:23]([CH3:24])[CH3:22])=[O:20])[CH:13]=2)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1
Reactant: O=C(Cl)c1cc(-c2ncc(C(F)(F)F)cc2Cl)ccc1Cl
Reactant: CNC
Solvent: ClCCl
Solvent: O
Product: CN(C)C(=O)c1cc(-c2ncc(C(F)(F)F)cc2Cl)ccc1Cl
Temperature: 0 °C
Reaction time: 4 h

Procedure:
A solution of 3.5 g of 3-chloro-2-(4-chloro-3-chloroformylphenyl)-5-trifluoromethylpyridine in 10 ml of methylene chloride was added dropwise to 75 ml of a 40% by weight aqueous dimethylamine solution cooled to 0° C. The mixture was stirred at 0 to 5° C. for 4 hours and then diluted with 225 ml of water, after which it was extracted three times with 100 ml of tert-butyl methyl ether each time. The combined organic phases were washed twice with 100 ml of water each time, dried over sodium sulfate and concentrated. The residue was chromatographed on silica gel with cyclohexane/ethyl acetate (7:3). Yield: 2.2 g (61%) of colorless crystals; melting point: 90°-91° C.
Reaction SMILES: COCCOC[O:7][C:8]1[CH:9]=[C:10]([CH:20]=[CH:21][CH:22]=1)[CH2:11][O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO.CCOC(C)=O>[N:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[CH2:13][O:12][CH2:11][C:10]1[CH:9]=[C:8]([OH:7])[CH:22]=[CH:21][CH:20]=1
Reactant: COCCOCOc1cccc(COCc2ccccn2)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CO
Solvent: CCOC(C)=O
Product: Oc1cccc(COCc2ccccn2)c1
Temperature: 60 °C
Reaction time: 1.5 h

Procedure:
To a solution of 2-[3-(2-methoxy-ethoxymethoxy)-benzyloxymethyl]-pyridine (171 mg, 0.56 mmol, example 73) in CH3OH (1.9 mL) is added p-toluenesulfonic acid monohydrate (148 mg, 0.78 mmol). The mixture is heated to 60° C. and stirred for 1.5 hrs, then cooled to room temperature and diluted with EtOAc. The organic layer is washed with sat NaHCO3, brine, then dried over MgSO4 and concentrated to give the title compound as a white crystalline solid. MS (ESI) 216 (M+H)+.
Reaction SMILES: C(OC(=O)[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([S:19](=[O:22])(=[O:21])[NH2:20])=[CH:15][CH:14]=1)(C)(C)C>C(O)(C(F)(F)F)=O.C(Cl)Cl>[NH2:7][CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([S:19]([NH2:20])(=[O:21])=[O:22])=[CH:15][CH:14]=1
Reactant: CC(C)(C)OC(=O)NCCCCOc1ccc(S(N)(=O)=O)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: NCCCCOc1ccc(S(N)(=O)=O)cc1
Yield: 177.4 %

Procedure:
A solution of tert-butyl(4-(4-sulfamoylphenoxy)butyl)carbamate (0.72 g, 2.09 mmol) in TFA (5.0 mL) and DCM (5.0 mL) was stirred at rt for overnight. After the solvent was evaporated under a steam of N2, the reaction mixture was dissolved in water (20.0 mL) and acetonitrile (5.0 mL) and lyophilized to afford 4-(4-aminobutoxy)benzenesulfonamide as a yellow solid (0.906 g) containing TFA. 1H NMR (400 MHz, DMSO) 7.74-7.72 (m, 4H), 7.20 (s, 2H), 7.06 (d, 2H), 4.06 (t, 2H), 2.89-2.82 (m, 2H), 1.80-1.75 (m, 2H), 1.71-1.65 (m, 2H); MS (ESI), 245.1 (M+H)+.
Reaction SMILES: Cl.[CH3:2][NH:3][CH:4]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([N+:13]([O-:15])=[O:14])[CH:10]=2)[CH2:5]1.Br[CH2:17][C:18]1[O:19][C:20]2[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][C:21]=2[CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)C>[CH3:2][N:3]([CH:4]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([N+:13]([O-:15])=[O:14])[CH:10]=2)[CH2:5]1)[CH2:17][C:18]1[O:19][C:20]2[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][C:21]=2[CH:22]=1
Reactant: O=[N+]([O-])c1ccc2oc(CBr)cc2c1
Reactant: CNC1Cc2ccc([N+](=O)[O-])cc2C1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: CN(Cc1cc2cc([N+](=O)[O-])ccc2o1)C1Cc2ccc([N+](=O)[O-])cc2C1
Reaction time: 5 h

Procedure:
2-Methylamino-5-nitroindane hydrochloride (0.28 g), 2-bromomethyl-5-nitrobenzofuran (0.31 g) and potassium carbonate (0.5 g) were stirred at room temperature in ethanol for 18 hours. A further portion of 2-bromomethyl-5-nitrobenzofuran (0.05 g) was then added and stirring was continued at room temperature for 5 hours. The solvent was evaporated in vacuo and the residue was dissolved in methylene chloride, washed with water, dried (MgSO4) and evaporated to give an oil which was purified by column chromatography on silica eluting with methylene chloride containing methanol (0% up to 1%). The product-containing fractions were combined and evaporated to give a gum which was triturated with diisopropyl ether and the precipitate was filtered off to give the title compound, yield 0.35 g, m.p. 109°-111°.
Reaction SMILES: [C:1]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:6]=[CH:5][C:4]([CH:7]([C:12]2([OH:16])[CH2:15][O:14][CH2:13]2)[S:8]([NH2:11])(=[O:10])=[O:9])=[CH:3][CH:2]=1.[CH2:23]([O:25][C:26](OCC)(OCC)OCC)C>C(O)(=O)C>[C:1]1([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:2]=[CH:3][C:4]([CH:7]2[C:12]3([CH2:13][O:14][CH2:15]3)[O:16][C:23]([O:25][CH3:26])=[N:11][S:8]2(=[O:10])=[O:9])=[CH:5][CH:6]=1
Reactant: CCOC(OCC)(OCC)OCC
Reactant: NS(=O)(=O)C(c1ccc(-c2ccccc2)cc1)C1(O)COC1
Solvent: CC(=O)O
Product: COC1=NS(=O)(=O)C(c2ccc(-c3ccccc3)cc2)C2(COC2)O1
Temperature: 90 °C
Reaction time: 3 h

Procedure:
A mixture of 0.17 g of biphenyl-4-yl-(3-hydroxyoxetan-3-yl)methanesulfonamide in 4 ml of tetraethoxymethane and 1 ml of acetic acid was stirred at 90° C. for 3 hours. The solvent was removed under reduced pressure. This gave the crude product, which was used without further purification.
Reaction SMILES: [CH:1]1([NH2:4])[CH2:3][CH2:2]1.[O:5]1[CH2:32][CH:6]1[CH2:7][O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](=[O:31])[C:14]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[C:15]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[O:16]2)=[CH:11][CH:10]=1>>[CH:1]1([NH:4][CH2:32][CH:6]([OH:5])[CH2:7][O:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13](=[O:31])[C:14]([C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)=[C:15]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[O:16]3)=[CH:11][CH:10]=2)[CH2:3][CH2:2]1
Reactant: NC1CC1
Reactant: O=c1c(-c2ccccc2)c(-c2ccccc2)oc2cc(OCC3CO3)ccc12
Product: O=c1c(-c2ccccc2)c(-c2ccccc2)oc2cc(OCC(O)CNC3CC3)ccc12
Yield: 25 %

Procedure:
The amine was prepared according to Method B from cyclopropylamine and 7-(2,3-epoxypropoxy)-2,3-diphenylchromone and purified by high pressure liquid chromatography to give white crystals, m.p. 135°-137° (MeOH-ether), in 25% yield.
Reaction SMILES: [C:1]([C:9]12[O:15]C1[O:13][C:12]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:11][C:10]2=[O:21])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(O)=O.O>[OH:15][C:9]1[C:10](=[O:21])[CH:11]=[C:12]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[O:13][C:1]=1[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)C1=CC(=O)C2(C(=O)c3ccccc3)OC2O1
Solvent: O
Solvent: O=CO
Product: CCOC(=O)c1cc(=O)c(O)c(-c2ccccc2)o1

Procedure:
A solution of ethyl 6-benzoyl-5-oxo-2,7-dioxabicyclo[4.1.0]hept-3-ene-3-carboxylate (3.5 g) in 98-100% formic acid (50 ml) was heated under reflux for 11/2 hours, cooled, diluted with water and extracted with ethyl acetate. The extract was washed with excess sodium bicarbonate solution, dried and evaporated and the solid residue was crystallised twice from chloroform-petroleum ether 60°-80° C. to give the title product (mp 155°-157° C.).
Reaction SMILES: O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.O1CCC[CH2:16]1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C([Li])CCC.CCCCCC.C(OCC)(=O)C>[CH2:16]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1
Reactant: C1CCOC1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: C=C1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 0.83 h

Procedure:
To a solution of 986 mg of methyltriphenylphosphonium bromide in 20 ml of tetrahydrofuran, 1.87 ml of 1.63 M n-butyl lithium/hexane solution was added dropwise at 0° C., under cooling with ice. The temperature then was immediately raised to room temperature, and the system was stirred for 50 minutes. The reaction liquid was again cooled to 0° C., to which a solution of 500 mg of t-butyl 4-oxotetrahydropyridine-1(2H)-carboxylate in 5 ml of tetrahydrofuran was added dropwise, followed by an hour's stirring at the same temperature. The reaction liquid was diluted with ethyl acetate, washed successively with saturated aqueous ammonium chloride solution and saturated brine, and dried over anhydrous sodium sulfate. Distilling the solvent off under reduced pressure, the resulting residue was purified on silica gel column chromatography (eluent: hexane/ethyl acetate=5/1) to provide 192 mg of the title compound.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:14]([NH:16][C:17]([C:19]2[N:20]=[C:21](Cl)[O:22][CH:23]=2)=[O:18])[CH3:15])[CH:5]=[C:6]([F:13])[C:7]=1[NH:8][S:9]([CH3:12])(=[O:11])=[O:10].[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][C:27]=1[OH:36]>>[F:1][C:2]1[CH:3]=[C:4]([CH:14]([NH:16][C:17]([C:19]2[N:20]=[C:21]([O:36][C:27]3[CH:28]=[C:29]([C:32]([F:33])([F:34])[F:35])[CH:30]=[CH:31][C:26]=3[Cl:25])[O:22][CH:23]=2)=[O:18])[CH3:15])[CH:5]=[C:6]([F:13])[C:7]=1[NH:8][S:9]([CH3:12])(=[O:11])=[O:10]
Reactant: Oc1cc(C(F)(F)F)ccc1Cl
Reactant: CC(NC(=O)c1coc(Cl)n1)c1cc(F)c(NS(C)(=O)=O)c(F)c1
Product: CC(NC(=O)c1coc(Oc2cc(C(F)(F)F)ccc2Cl)n1)c1cc(F)c(NS(C)(=O)=O)c(F)c1
Yield: 71.2 %

Procedure:
2-Chloro-oxazole-4-carboxylic acid [1-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-amide (50 mg, 0.13 mmol) was reacted with 2-chloro-5-trifluoromethyl-phenol (52 mg, 0.26 mmol) to give the title compound (50 mg, 71%) after purification by column chromatography (gradient 12% to 100% EtOAc in n-hexane).
Reaction SMILES: CO[C:3]1[N:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]3[CH:19]=[N:20][C:21]([CH2:24][N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[CH:22][CH:23]=3)[N:12]=2)=[CH:7][C:4]=1[C:5]#[N:6].C1(OP(Cl)([Cl:40])=O)C=CC=CC=1>O>[Cl:40][C:3]1[N:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]3[CH:19]=[N:20][C:21]([CH2:24][N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[CH:22][CH:23]=3)[N:12]=2)=[CH:7][C:4]=1[C:5]#[N:6]
Reactant: O=P(Cl)(Cl)Oc1ccccc1
Reactant: COc1ncc(-c2ccnc(Nc3ccc(CN4CCOCC4)nc3)n2)cc1C#N
Solvent: O
Product: N#Cc1cc(-c2ccnc(Nc3ccc(CN4CCOCC4)nc3)n2)cnc1Cl
Temperature: 130 °C
Yield: 46 %

Procedure:
A mixture of compound 17 (1.5 g, 3.7 mmol) and phenylphosphoro dichloridate (5 mL) was heated at 130° C. for 5 h. The reaction mixture was cooled to rt, diluted with cold water (10 mL), cooled to 0° C., quenched with saturated NaHCO3 solution and extracted with EtOAc (2×50 mL). The combined organic layer was washed with brine (50 mL), dried (Na2SO4) and evaporated. The crude compound was purified by trituration with EtOAc to obtain 18 (0.7 g, 46%) as a pale brown solid. Rf: 0.5 (10% MeOH/DCM); (m/z): 408 [M+1]+; 1H NMR (400 MHz, DMSO-d6): δ10.01 (1H, s), 9.40 (1H, d, J=2.4 Hz), 9.11 (1H, d, J=2.4 Hz), 8.85 (1H, d, J=2.4 Hz), 8.70 (1H, d, J=5.2 Hz), 8.21-8.18 (1H, dd, J=2.4, 8.8 Hz), 7.62 (1H, d, J=5.6 Hz), 7.40 (1H, d, J=8.4 Hz), 3.59-3.54 (6H, m), 2.46-2.41 (4H, m).
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][C:5]([F:9])=[CH:4][N:3]=1.Br[CH:11]([CH3:15])[C:12](=O)[CH3:13]>C(O)C>[NH2:8][C:7]1[C:2]2[N:3]([C:11]([CH3:15])=[C:12]([CH3:13])[N:1]=2)[CH:4]=[C:5]([F:9])[CH:6]=1
Reactant: CC(=O)C(C)Br
Reactant: Nc1cc(F)cnc1N
Solvent: CCO
Product: Cc1nc2c(N)cc(F)cn2c1C
Yield: 37.2 %

Procedure:
A mixture of 2,3-diamino-5-fluoropyridine (0.3 g, 2.4 mmol) and 3-bromo-2-butanon (0.36 g, 2.4 mmol) in ethanol (20 ml) was refluxed for 10 h. The solvent was evaporated under reduced pressure. The residue was dissolved in methylene chloride and was treated with a bicarbonate solution. The organic layer was separated, dried over sodium sulfate and evaporated under reduced pressure. The residue was purified with column chromatography on silica gel with methanol:methylene chloride (1:20) as eluent to give 0.16 g (37%) of the title compound.
Reaction SMILES: O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[CH3:15][NH2:16].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1>[CH3:15][NH:16][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: CN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: C1CCOC1
Product: CNC1CCN(C(=O)OC(C)(C)C)CC1
Reaction time: 8 h

Procedure:
To a solution of tert-butyl 4-oxo-1-piperidinecarboxylate (0.50 g, 2.5 mmol, Aldrich) and 2.0 M methylamine in Tetrahydrofuran (10. mL, 20. mmol, Aldrich) was added sodium triacetoxyborohydride (1.3 g, 6.3 mmol). After stirring of the suspension overnight, the reaction was quenched with water and stirred for 1 hour. Brine was added and the product was extracted with two portions of DCM. The combined organic extracts were dried over sodium sulfate, filtered and concentrated. The product was used without further purification in Step 2. LCMS (M+H)+: 215.2.
Reaction SMILES: [CH2:1]([O:19][CH2:20][CH:21]([CH2:33][O:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42]/[CH:43]=[CH:44]\[CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH3:52])OS(C1C=CC(C)=CC=1)(=O)=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[N-:53]=[N+:54]=[N-:55].[Li+]>CN(C)C=O>[CH2:1]([O:19][CH2:20][CH:21]([N:53]=[N+:54]=[N-:55])[CH2:33][O:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42]/[CH:43]=[CH:44]\[CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH3:52])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: [N-]=[N+]=[N-]
Reactant: CCCCCCCC/C=C\CCCCCCCCOCC(COCCCCCCCC/C=C\CCCCCCCC)OS(=O)(=O)c1ccc(C)cc1
Agent: [Li+]
Solvent: CN(C)C=O
Product: CCCCCCCC/C=C\CCCCCCCCOCC(COCCCCCCCC/C=C\CCCCCCCC)N=[N+]=[N-]
Temperature: 100 °C
Reaction time: 2 h
Yield: 100.8 %

Procedure:
A mixture of 150 mg (80%) of the above 1,3-O-dioleyl-2-O-(p-toluenesulfonyl)glycerol, 30 mg (0.6 mmol) of lithium azide, and 5 ml of N,N-dimethylformamide was stirred at 100 ° C. for 2 hours. After cooling, the solvent was distilled off and the residue was diluted with water and extracted with ether. The extract was washed with water, dried, and concentrated to provide 125 mg (99%) of 1,3-dioleyloxy-2-propyl azide as light-brown oil.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH:14]=[C:13]([CH3:15])[N:12]=[CH:11]2)=[C:6]([CH:9]=1)[C:7]#[N:8].[Cl:16][C:17]1[CH:29]=[CH:28][C:20]([CH2:21][N:22]2[CH:26]=[N:25][C:24]([NH2:27])=[N:23]2)=[CH:19][CH:18]=1>>[Cl:16][C:17]1[CH:29]=[CH:28][C:20]([CH2:21][N:22]2[CH:26]=[N:25][C:24]([NH:27][C:2]3[CH:3]=[CH:4][C:5]([N:10]4[CH:14]=[C:13]([CH3:15])[N:12]=[CH:11]4)=[C:6]([CH:9]=3)[C:7]#[N:8])=[N:23]2)=[CH:19][CH:18]=1
Reactant: Nc1ncn(Cc2ccc(Cl)cc2)n1
Reactant: Cc1cn(-c2ccc(Br)cc2C#N)cn1
Product: Cc1cn(-c2ccc(Nc3ncn(Cc4ccc(Cl)cc4)n3)cc2C#N)cn1

Procedure:
Prepared in analogy to example 1b) starting with 5-bromo-2-(4-methyl-imidazol-1-yl)-benzonitrile and 1-(4-chloro-benzyl)-1H-[1,2,4]triazol-3-ylamine. The title compound was obtained as a colorless solid (Yield=49%). MS ISP (m/e): 390.2 & 392.0 (100 & 48) [(M+H)+].
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]Br.[CH2:19]([N:22]([CH2:26][CH2:27][CH3:28])[CH2:23][CH2:24][CH3:25])[CH2:20][CH3:21]>>[Br-:1].[Br-:1].[CH2:19]([N+:22]([CH2:26][CH2:27][CH3:28])([CH2:23][CH2:24][CH3:25])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][N+:22]([CH2:26][CH2:27][CH3:28])([CH2:23][CH2:24][CH3:25])[CH2:19][CH2:20][CH3:21])[CH2:20][CH3:21]
Reactant: CCCN(CCC)CCC
Reactant: BrCCCCCCCCCCCCCCCCBr
Product: CCC[N+](CCC)(CCC)CCCCCCCCCCCCCCCC[N+](CCC)(CCC)CCC
Product: [Br-]

Procedure:
The crystalline form of the derivative defined in the title is obtained using the -1,16-dibromohexadecane derivative and tripropylamine according to the conditions described above, M.P. 227° C.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=O)[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[C:8]([CH3:12])[O:9]2)=[CH:4][CH:3]=1.O.[NH2:21][NH2:22]>C(O)C>[CH3:12][C:8]1[NH:22][N:21]=[C:6]([C:5]2[CH:4]=[CH:3][C:2]([OH:1])=[CH:11][C:10]=2[OH:9])[C:7]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Cc1oc2cc(O)ccc2c(=O)c1-c1ccccc1
Reactant: NN
Solvent: O
Solvent: CCO
Product: Cc1[nH]nc(-c2ccc(O)cc2O)c1-c1ccccc1

Procedure:
This compounds was synthesised in the same manner as described above. 7-Hydroxy-2-methyl-3-phenyl-chromen-4-one (0.5 g, 1.70 mmol), hydrazine hydrate (5 ml), ethanol (10 ml). The quenched solution was extracted into ethyl acetate, washed (water), dried (MgSO4), and the solvent removed under vacuum to give a yellow oil which was purified by column chromatography to give 4-(5-Methyl-4-phenyl-1H-pyrazol-3-yl)-benzene-1,3-diol as an off white solid (0.37 g, 88%); Rf 0.7 Cf SM 0.8 ethyl acetate/hexane (80/20).
Reaction SMILES: C([O:4][C@H:5]1[CH2:29][CH2:28][C@@:27]2([CH3:30])[C@@H:7]([CH2:8][CH2:9][C:10]3[C@@H:26]2[CH2:25][CH2:24][C@@:23]2([CH3:31])[C:11]=3[C@H:12]([O:32][CH3:33])[CH2:13][C@@H:14]2[C@H:15]([CH3:22])[CH2:16][CH2:17][CH2:18][CH:19]([CH3:21])[CH3:20])[CH2:6]1)(=O)C.C1COCC1.[OH-].[Na+].O>CO>[CH3:33][O:32][C@H:12]1[C:11]2[C@:23]([CH3:31])([CH2:24][CH2:25][C@H:26]3[C:10]=2[CH2:9][CH2:8][C@@H:7]2[C@:27]3([CH3:30])[CH2:28][CH2:29][C@H:5]([OH:4])[CH2:6]2)[C@@H:14]([C@H:15]([CH3:22])[CH2:16][CH2:17][CH2:18][CH:19]([CH3:21])[CH3:20])[CH2:13]1
Reactant: CO[C@@H]1C[C@H]([C@H](C)CCCC(C)C)[C@@]2(C)CC[C@H]3C(=C12)CC[C@H]1C[C@@H](OC(C)=O)CC[C@@]13C
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: CO[C@@H]1C[C@H]([C@H](C)CCCC(C)C)[C@@]2(C)CC[C@H]3C(=C12)CC[C@H]1C[C@@H](O)CC[C@@]13C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To 30 (0.070 g, 0.15 mmol) dissolved in methanol (0.8 mL) and THF (0.4 mL) was added 2N sodium hydroxide (0.2 mL) and the reaction mixture was stirred at ambient temperature for 1 h. Some starting material was still present and the reaction mixture was stirred for an additional 2 h at 50° C. To the reaction mixture was added water (~10 mL). The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with water and saline and dried over sodium sulfate. Evaporation of the solvent afforded a white solid that was purified on a silica gel flash column (1×10 cm) and eluted with ethyl acetate/dichloromethane (1:9). Yield of pure compound 31, 0.057 g (89%) mp 127°-128° C. 1H NMR: δ4.21 (dd, 1H, J=6.5, 7.6 Hz), 3.67-3.59 (m, 1H), 3.27 (s, 3H) 2.72-2.68 (m, 1H). 2.26 (ddd, 1H, J=8.0, 8.1, 13.2 Hz), 0.98 (s, 3H), 0.93 (d, 3H, J=6.6 Hz), 0.87 (d, 3H, J=6.7), 0.867 (d, 3H, J=6.6 Hz), 0.74 (s, 3H). IR: 3263, 1336, 1283, 1212, 1131, 1092, 1041. EIMS (m/z): 416.
Reaction SMILES: [NH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[C:11](Cl)(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.O.Cl>N1C=CC=CC=1.CCOCC>[C:11]([N:1]1[C:10]2[CH:5]([CH2:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1)(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: c1ccc2c(c1)CCCN2
Reactant: O=C(Cl)c1ccccc1
Agent: Cl
Solvent: O
Solvent: CCOCC
Solvent: c1ccncc1
Product: O=C(c1ccccc1)N1CCCC2CC=CC=C21
Yield: 74.7 %

Procedure:
To a solution of 26.6 g (0.02 m) of tetrahydroquinoline in 50 ml of pyridine, cooled to 0° C., there were added 28.1 g (0.02 m) of benzoyl chloride dropwise and with stirring at a rate such the temperature was kept below -5° C. After addition was complete, the mixture was stirred at room temperature for 1 hour and then poured into a separatory funnel containing 500 ml of water and 50 ml of conc. hydrochloric acid. Ethyl ether (300 ml) was added to the funnel and the mixture shaken until all of the precipitated oil had dissolved in the ether. After washing with water, the ether layer was filtered through anhydrous calcium sulfate and evaporated to a volume of about 150 ml. Petroleum ether (100 ml) was added to the solution which was then cooled in a refrigerator to give 35.7 g (75% yield) of 1-benzoyltetrahydroquinoline as colorless crystals, m.p. 80°-81° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:30][C:31]([CH:33]2[CH2:36][N:35](C(OC(C)(C)C)=O)[CH2:34]2)=[O:32])[C:10](=[O:29])[N:11]2[CH2:16][CH2:15][CH:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:23]3[CH:27]=[CH:26][NH:25][C:24]3=[O:28])[CH2:13][CH2:12]2)=[CH:4][CH:3]=1.Cl>CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C@@H:9]([NH:30][C:31]([CH:33]2[CH2:34][NH:35][CH2:36]2)=[O:32])[C:10](=[O:29])[N:11]2[CH2:16][CH2:15][CH:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:23]3[CH:27]=[CH:26][NH:25][C:24]3=[O:28])[CH2:13][CH2:12]2)=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CC(C(=O)N[C@H](Cc2ccc(Cl)cc2)C(=O)N2CCC(c3ccccc3-n3cc[nH]c3=O)CC2)C1
Agent: Cl
Solvent: CCOC(C)=O
Product: O=C(N[C@H](Cc1ccc(Cl)cc1)C(=O)N1CCC(c2ccccc2-n2cc[nH]c2=O)CC1)C1CNC1
Reaction time: 0.5 h

Procedure:
The title compound was prepared according to the procedure described in Example 16 (Step b) using tert-butyl 3-[N-((1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-(4-[2-(2-oxo(4-imidazolinyl))phenyl]piperidyl)ethyl}carbamoyl]azetidinecarboxylate (Step a) (0.2 g, 0.33 mmol) and satd anhydrous HCl in EtOAc (20 mL). Purification by reverse phase preparative HPLC [Phenomenex; 5 μm 250×21.2 mm, 5% to 95% CH3CN (0.1% TFA) in H2O (0.1% TFA) over 30 min, then 100% CH3CN (0.1% TFA) for 2 min] provided the title compound (TFA salt) as a white solid (0.02 g) MS (ESI, pos. ion) m/z: 508 (M+1) Calc'd for C27H30ClN5O3: 507.20.