Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]=[C:2]1[S:6][C:5](=[NH:7])[N:4]([C:8]2[CH:21]=[CH:20][C:11]3[O:12][C:13]([F:19])([F:18])[C:14]([F:17])([F:16])[O:15][C:10]=3[CH:9]=2)[CH2:3]1.CCN(C(C)C)C(C)C.[CH3:31][CH:32]([CH3:37])[CH2:33][C:34](Cl)=[O:35]>C(#N)C.C(Cl)Cl>[CH3:31][CH:32]([CH3:37])[CH2:33][C:34](/[N:7]=[C:5]1\[S:6][C:2]([CH3:1])=[CH:3][N:4]\1[C:8]1[CH:21]=[CH:20][C:11]2[O:12][C:13]([F:19])([F:18])[C:14]([F:16])([F:17])[O:15][C:10]=2[CH:9]=1)=[O:35]
Reactant: CC(C)CC(=O)Cl
Reactant: C=C1CN(c2ccc3c(c2)OC(F)(F)C(F)(F)O3)C(=N)S1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CC#N
Product: Cc1cn(-c2ccc3c(c2)OC(F)(F)C(F)(F)O3)/c(=N/C(=O)CC(C)C)s1
Temperature: 65 °C

Procedure:
To a solution of 5-methylene-3-(2,2,3,3-tetrafluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)thiazolidin-2-imine (Example 22C, 0.14 g, 0.44 mmol) in acetonitrile (3 mL) was added Hunig's base (0.062 g, 0.48 mmol) followed by 3-methylbutanoyl chloride (0.08 g, 0.66 mmol). The mixture was heated for 12 hours at 65° C. The reaction mixture was cooled down and more 3-methylbutanoyl chloride (0.08 g, 0.66 mmol) was added. The mixture was heated again at 65° C. for 12 hours. After cooling off, the mixture was diluted with CH2Cl2 (50 mL) and washed with water and brine. The organic phase was dried over sodium sulfate, filtered and dried. After evaporation under reduced pressure the residue was chromatographed over silica using CH2Cl2 100%-5%MeOH/CH2Cl2 to supply the titled compound. 1H NMR (CDCl3) δ ppm 0.95 (6H), 2.20 (1H), 2.35 (3H), 2.40 (2H), 6.75 (1H), 7.20 (1H), 7.30 (1H), 7.40 (1H); MS (ESI) m/z 405(M+H)+.
Reaction SMILES: Cl[CH:2]1[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]1.[Mg].[Cl:10][C:11]1[CH:19]=[C:18]2[C:14]([CH2:15][C:16]([CH3:22])([CH3:21])[C:17]2=[O:20])=[CH:13][CH:12]=1.[Cl-].[NH4+]>O1CCCC1>[Cl:10][C:11]1[CH:19]=[C:18]2[C:14]([CH2:15][C:16]([CH3:22])([CH3:21])[C:17]2([CH:2]2[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]2)[OH:20])=[CH:13][CH:12]=1
Reactant: CN1CCC(Cl)CC1
Reactant: CC1(C)Cc2ccc(Cl)cc2C1=O
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CN1CCC(C2(O)c3cc(Cl)ccc3CC2(C)C)CC1

Procedure:
A Grignard reagent is prepared from 14.0 g 4-chloro-N-methylpiperidine and 2.6 g magnesium in 200 ml boiling tetrahydrofuran. After cooling, a solution of 10.0 g 6-chloro-2,2-dimethyl-indanone in 50 ml tetrahydrofuran is added dropwise at 5°-10°, and the reaction mixture is refluxed for 6 hours. After cooling, a 10% aqueous solution of ammonium chloride is added and the mixture is extracted with toluene. The toluene phase is dried and evaporated, to give 6-chloro-2,2-dimethyl-1-(1-methyl-4-piperidinyl)indan-1-ol (m.p. 181°-182°).
Reaction SMILES: [Br:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][NH:7][CH2:8][C:9]([NH:11][CH:12]2[CH2:14][CH2:13]2)=[O:10])=[CH:4][CH:3]=1.[C:17](N1C=CN=C1)(N1C=CN=C1)=[O:18].C(=O)(O)[O-].[Na+]>C(#N)C.CN(C)C1C=CN=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[CH2:8][C:9](=[O:10])[N:11]([CH:12]3[CH2:13][CH2:14]3)[C:17]2=[O:18])=[CH:15][CH:16]=1
Reactant: O=C(CNCc1ccc(Br)cc1)NC1CC1
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: CN(C)c1ccncc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Product: O=C1CN(Cc2ccc(Br)cc2)C(=O)N1C1CC1
Temperature: 60 °C
Reaction time: 8 h
Yield: 94.9 %

Procedure:
To a solution of 2-(4-bromobenzylamino)-N-cyclopropylacetamide (7H4) (28.3 mmol, 8.0 g) in acetonitrile (200 ml) was added carbonyldiimidazole (56.5 mmol, 9.16 g) and 4-dimethylaminopyridine (56.5 mmol, 6.90 g). The reaction mixture was heated to 60° C. and stirred overnight before cooling to room temperature. Saturated sodium bicarbonate solution was added and the mixture extracted with EtOAc (×3). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated and the residue purified on silica eluting with heptane/acetone 9:1 to 7:3 to give 1-(4-bromobenzyl)-3-cyclopropylimidazolidine-2,4-dione (7H5) 8.3 g (98%); 1H NMR (400 MHz, CDCl3) δ 7.50 (d, 2H) 7.13 (d, 2H) 4.50 (s, 2H) 3.66 (s, 2H) 2.62 (m, 1H) 0.97 (d, 4H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[CH:15]=[C:14]([NH:16][CH3:17])[N:13]=[CH:12][N:11]=1.[Cl:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:20]=1[N:26]=[C:27]=[O:28]>>[Cl:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:20]=1[NH:26][C:27](=[O:28])[N:16]([C:14]1[CH:15]=[C:10]([NH:9][C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])[N:11]=[CH:12][N:13]=1)[CH3:17]
Reactant: CNc1cc(Nc2ccc(F)cc2F)ncn1
Reactant: O=C=Nc1c(Cl)cccc1Cl
Product: CN(C(=O)Nc1c(Cl)cccc1Cl)c1cc(Nc2ccc(F)cc2F)ncn1

Procedure:
The title compound is prepared analogously as described in Example 105B from N-(2,4-difluoro-phenyl)-N′-methyl-pyrimidine-4,6-diamine and 2,6-dichlorophenyl isocyanate.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:12])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.[NH2:13][CH2:14][CH:15]([OH:17])[CH3:16].ClCCl>C(O)CCC.O>[Cl:12][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:13][CH2:14][CH:15]([OH:17])[CH3:16])=[CH:3][CH:4]=[N:5]2)=[CH:10][CH:9]=1
Reactant: Clc1ccc2c(Cl)ccnc2c1
Reactant: CC(O)CN
Solvent: O
Solvent: ClCCl
Solvent: CCCCO
Product: CC(O)CNc1ccnc2cc(Cl)ccc12
Temperature: 25 °C

Procedure:
A mixture of 20 g of 4,7-dichloroquinoline and 16 g of 1-amino-2-propanol in 60 ml of butanol was stirred at reflux until the reaction was complete (6 hours). The reaction mixture was cooled down to room temperature and diluted with water. The organics were exracted into dichloromethane (3×300 ml). Drying over anhydrous magnesium sulfate and evaporation of solvents resulted in an oil which crystallized upon standing. The crystals were isolated by filtration and washed with ether to yield a solid which was recrystallized from isopropanol. The resultant crystals had a melting point of 168°-169.5° C. and the yield was 15 g.
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].CN(C=O)C.C(Cl)(=O)C(Cl)=O.[CH2:19]([NH2:39])[CH2:20][CH2:21][CH2:22]/[CH:23]=[CH:24]\[CH2:25]/[CH:26]=[CH:27]\[CH2:28]/[CH:29]=[CH:30]\[CH2:31]/[CH:32]=[CH:33]\[CH2:34][CH2:35][CH2:36][CH2:37][CH3:38]>C(Cl)Cl>[CH2:19]([NH2:39])[CH2:20][CH2:21][CH2:22]/[CH:23]=[CH:24]\[CH2:25]/[CH:26]=[CH:27]\[CH2:28]/[CH:29]=[CH:30]\[CH2:31]/[CH:32]=[CH:33]\[CH2:34][CH2:35][CH2:36][CH2:37][CH3:38].[F:1][C:2]([F:7])([F:6])[C:3]([O-:5])=[O:4]
Reactant: O=C(O)C(F)(F)F
Agent: CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCCN
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C([O-])C(F)(F)F
Reaction time: 0.33 h

Procedure:
To a magnetically stirred solution of 69 mg (0.6 mmol) of trifluoroacetic acid, in 2 ml of dry methylene chloride, at 0° C., 0.046 ml (0.6 mmol) of dry DMF was added and then 0.3 ml (0.6 mmol) of 2.0 M solution of oxalyl chloride in methylene chloride, dropwise. The reaction mixture was stirred for 20 min and then a solution of 172 mg (0.6 mmol) of arachidonyl amine in 2 ml of methylene chloride was added and the reaction was stirred for 2 hrs at ambient temperature. The product was purified with silica gel column chromatography (eluents: petroleum ether/ethyl acetate, up to 50% ethyl acetate). Evaporation of the solvent, followed by Millipore filtration of a CH2Cl2 solution of the product gave 153 mg (0.4 mmol, 67% yield) of arachidonyl-amine-trifluoroacetate as a colorless oil.
Reaction SMILES: BrBr.[CH2:3]([O:5][C:6]([CH:8]1[CH2:19][N:18]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[C:11]2[N:12]=[C:13]([S:16][CH3:17])[N:14]=[CH:15][C:10]=2[C:9]1=[O:26])=[O:7])[CH3:4].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH2:3]([O:5][C:6]([C:8]1[C:9](=[O:26])[C:10]2[CH:15]=[N:14][C:13]([S:16][CH3:17])=[N:12][C:11]=2[N:18]([CH:20]2[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]2)[CH:19]=1)=[O:7])[CH3:4]
Reactant: CCOC(=O)C1CN(C2CCCCC2)c2nc(SC)ncc2C1=O
Agent: BrBr
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCOC(=O)c1cn(C2CCCCC2)c2nc(SC)ncc2c1=O
Reaction time: 0.08 h
Yield: 102 %

Procedure:
Bromine (0.15 g, 0.94 mmol) was added to a solution of 8-cyclohexyl-2-methylsulfanyl-5-oxo-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (0.28 g, 0.79 mmol) in DCM (10 mL). After 5 min, the solution was concentrated and the crude residue was redissolved in DCM (10 mL) and diisopropylethylamine (0.42 mL, 2.4 mmol) was added. After 15 h, the reaction mixture was partitioned between water and DCM, the organic layer was separated, dried (MgSO4) and concentrated to provide 0.28 g (87%) of the title compound.). Mass Spectrum (LCMS, ESI pos.) Calcd. For C17H21N3O3S: 347.13, found: (M+H) 348.3.
Reaction SMILES: [CH3:1][C:2]1([CH3:12])[C@@H:4]([CH:5]=[C:6]([CH3:8])[CH3:7])[C@@H:3]1[C:9](O)=[O:10].S(Cl)([Cl:15])=O>CCCCCC>[CH3:1][C:2]1([CH3:12])[C@@H:4]([CH:5]=[C:6]([CH3:8])[CH3:7])[C@@H:3]1[C:9]([Cl:15])=[O:10]
Reactant: O=S(Cl)Cl
Reactant: CC(C)=C[C@H]1[C@H](C(=O)O)C1(C)C
Solvent: CCCCCC
Product: CC(C)=C[C@H]1[C@H](C(=O)Cl)C1(C)C
Reaction time: 0.5 h
Yield: 97.3 %

Procedure:
In a 300 ml flask, there were charged (-)-trans-2,2-dimethyl-3-isobutenylcyclopropane-1-carboxylic acid (50.0 g) and n-hexane (50 g), and thionyl chloride (41.0 g) was added thereto from a dropping funnel over a period of 30 minutes with stirring under reflux. After completion of the addition, stirring was continued for an additional 2.5 hours, and then the solvent and excess of the thionyl chloride were removed by distillation. The residue was distilled to obtain (-)-trans-2,2-dimethyl-3-isobutenylcyclopropane-1-carboxylic acid chloride (54.0 g) having a boiling point of 50° C./0.5 mmHg to 56° C./0.6 mmHg.
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[O:3][C:4]1[CH:5]=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([CH:16]=[O:17])=[CH:12][CH:11]=2)[CH:7]=[CH:8][CH:9]=1.CC(C)=[O:22]>>[F:1][C:2]([F:18])([F:19])[O:3][C:4]1[CH:5]=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([OH:22])=[O:17])=[CH:12][CH:11]=2)[CH:7]=[CH:8][CH:9]=1
Reactant: O=Cc1ccc(-c2cccc(OC(F)(F)F)c2)cc1
Reactant: CC(C)=O
Product: O=C(O)c1ccc(-c2cccc(OC(F)(F)F)c2)cc1
Yield: 82 %

Procedure:
To a cold solution of 3′-trifluoromethoxy-biphenyl-4-carbaldehyde (0.8 g, 3.0 mmol) in acetone (10 mL) the Jone's reagent was added slowly at 0° C. until reaction completes. Acetone was removed completely and diluted with water. The mixture was extracted with ethyl acetate and the combined organic layers were washed with water and brine, dried over sodium sulphate and concentrated to obtain the title compound (0.7 g, 82%).
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:16]=[C:17]([CH:30]=[CH:31][CH:32]=1)[CH2:18][S:19][C:20]1[CH:21]=[C:22]([CH:27]=[CH:28][CH:29]=1)[C:23](OC)=[O:24].O1CCCC1.[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl>O>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:16]=[C:17]([CH:30]=[CH:31][CH:32]=1)[CH2:18][S:19][C:20]1[CH:21]=[C:22]([CH:27]=[CH:28][CH:29]=1)[CH:23]=[O:24]
Reactant: COC(=O)c1cccc(SCc2cccc(OCc3nc(-c4ccccc4)oc3C)c2)c1
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: O
Solvent: C1CCOC1
Product: Cc1oc(-c2ccccc2)nc1COc1cccc(CSc2cccc(C=O)c2)c1
Reaction time: 2 h
Yield: 75.5 %

Procedure:
To a mixture of methyl 3-[3-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzylthio]benzoate (2.20 g) and tetrahydrofuran (80 mL) was added lithium aluminum hydride (0.19 g) under ice-cooling, and the mixture was stirred for 2 hrs. The reaction mixture was poured into iced water, acidified with 2N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated. The obtained oil was dissolved in toluene (80 mL). Manganese dioxide (6.0 g) was added to the mixture and the mixture was stirred at room temperature for 2 hrs. The reaction mixture was filtrated and the filtrate was concentrated. The residue was subjected to silica gel column chromatography to give 3-[3-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzylthio]benzaldehyde as an oil (1.55 g, yield 76%) from a fraction eluted with ethyl acetate-hexane (1:3, v/v).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:27])[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:20][CH2:19][C:18]3[N:17]=[C:16]4[CH:21]=[C:22]([Cl:25])[CH:23]=[CH:24][C:15]4=[C:14](Cl)[C:13]=3[CH2:12]2)=[CH:7][CH:6]=1)[CH3:2].[C:28]1([NH:34][NH2:35])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.Cl.C([O-])([O-])=O.[Na+].[Na+]>CO.CCOCC.C(O)C>[CH2:1]([O:3][C:4](=[O:27])[C:5]1[CH:6]=[CH:7][C:8]([NH:11][CH2:20][CH2:19][C:18]2[C:13]3=[CH:12][N:34]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[N:35]=[C:14]3[C:15]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:16]=3[N:17]=2)=[CH:9][CH:10]=1)[CH3:2]
Reactant: NNc1ccccc1
Reactant: CCOC(=O)c1ccc(N2CCc3nc4cc(Cl)ccc4c(Cl)c3C2)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOCC
Solvent: CCO
Solvent: CO
Product: CCOC(=O)c1ccc(NCCc2nc3cc(Cl)ccc3c3nn(-c4ccccc4)cc23)cc1
Yield: 25.7 %

Procedure:
A mixture of 1 g (2.5 mmol) of the compound of step C. above, 0.539 ml (5.48 mmol) of phenylhydrazine, 0.75 ml of conc. hydrochloric acid, and 30 ml of absolute ethanol is stirred under reflux for 6 hrs. The cooled precipitate is dissolved in methanol and treated with a Na2CO3 solution. The precipitate is collected and washed with water to yield 0.388 of a brown solid. Trituration with ether affords 0.303 g (26%) of the title compound as a light brown solid: m.p. 170°-172° C.; IR (KBr) 3320, 1687, and 1604 cm-1 ; NMR (DMSO-d6) δ 9.56 (s, 1H), 8.27 (d, 1H), 8.17 (d, 2H), 8.07 (s, 1H), 7.70 (m, 5H), 7.54 (t, 1H), 6.70 (d, 2H), 4.23 (q, 2H), 3.78 (m, 2H), 3.46 (t, 2H), 1.26 (t, 3H).
Reaction SMILES: [OH:1][N:2]1[C:6](=[O:7])[C:5]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:4]2[C:3]1=[O:12].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22]>CS(C)=O>[C:24]([O:23][C:21](=[O:22])[CH2:20][O:1][N:2]1[C:3](=[O:12])[C:4]2[C:5](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]1=[O:7])([CH3:27])([CH3:26])[CH3:25]
Reactant: O=C1c2ccccc2C(=O)N1O
Reactant: CC(C)(C)OC(=O)CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CC(C)(C)OC(=O)CON1C(=O)c2ccccc2C1=O
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 93.1 %

Procedure:
To a solution of 49 g of N-hydroxyphthalimide in 25 ml of dimethyl sulfoxide at 5° C., was added portionwise 27.6 g of potassium carbonate. After 10 minutes of stirring the reaction mixture was present as a red slurry to which 75 g of tert-butyl chloroacetate was added dropwise over 1 hour at 5° C. The resulting reaction mixture was stirred for 18 hours and poured into ice water. The solid product was filtered, dissolved in methylene chloride and washed with water. The methylene chloride phase was dried over magnesium sulfate, filtered and stripped and recrystallized from ethanol to give 77.5 g of 2-(2-tertbutoxy-2-oxoethoxy)-1H-isoindole-1,3(2H)-dione; m.p. 146°-7° C.
Reaction SMILES: [C:1]1([S:7]([CH:10]([C:17]2[O:18][C:19]([CH3:22])=[N:20][N:21]=2)[CH:11]2[CH2:15][CH2:14][C:13](=[O:16])[CH2:12]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[CH3:25]I>CN(C=O)C.[NH4+].[Cl-]>[C:1]1([S:7]([C:10]([CH:11]2[CH2:15][CH2:14][C:13](=[O:16])[CH2:12]2)([C:17]2[O:18][C:19]([CH3:22])=[N:20][N:21]=2)[CH3:25])(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Cc1nnc(C(C2CCC(=O)C2)S(=O)(=O)c2ccccc2)o1
Reactant: CI
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: Cc1nnc(C(C)(C2CCC(=O)C2)S(=O)(=O)c2ccccc2)o1
Reaction time: 2 h
Yield: 24.3 %

Procedure:
375 mg (1.17 mmol) of 3-[benzenesulfonyl-(5-methyl-[1,3,4]oxadiazol-2-yl)-methyl]-cyclopentanone in 10 mL of DMF, were treated with 52 mg (1.29 mmol, 1.1 eq) of NaH (55% in oil) over 30 min. 300 mg (2.32 mmol, 1.8 eq) of methyliodide were added, and after 2 hours, the reaction mixture was diluted with saturated aqueous NH4Cl and extracted with EtOAc. The combined organic phases were dried over Na2SO4, filtered and evaporated. The resulting two diastereomers were separated by column chromatography on silica gel with EtOAc/heptane 1:2, yielding 95 mg (24%) of (RS,SR)-3-[1-benzenesulfonyl-1-(5-methyl-[1,3,4]oxadiazol-2-yl)-ethyl]-cyclopentanone as a white solid, MS: 335 (MH+) and 90 mg (23%) of (RR,SS)-3-[1-benzenesulfonyl-1-(5-methyl-[1,3,4]oxadiazol-2-yl)-ethyl]-cyclopentanone as a white solid, MS: 335 (MH+).
Reaction SMILES: C(N1C2C(=CC=CC=2)C(O)(CC(=O)C2C=CC=CN=2)C1=O)CCC.[CH2:25]([N:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32](=[O:39])[C:31]1=[O:40])[CH2:26][CH:27]([CH3:29])[CH3:28].[NH:41]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[C:43]([C:50](=[O:52])[CH3:51])=[CH:42]1>>[NH:41]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[C:43]([C:50](=[O:52])[CH2:51][C:32]2([OH:39])[C:33]3[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=3)[N:30]([CH2:25][CH2:26][CH:27]([CH3:29])[CH3:28])[C:31]2=[O:40])=[CH:42]1
Reactant: CC(C)CCN1C(=O)C(=O)c2ccccc21
Reactant: CC(=O)c1c[nH]c2ccccc12
Agent: CCCCN1C(=O)C(O)(CC(=O)c2ccccn2)c2ccccc21
Product: CC(C)CCN1C(=O)C(O)(CC(=O)c2c[nH]c3ccccc23)c2ccccc21

Procedure:
This compound was made in a similar manner to 1-butyl-3-hydroxy-3-(2-oxo-2-(pyridin-2-yl)ethyl)indolin-2-one using 1-isopentylindoline-2,3-dione and commercially available 1-(1H-indol-3-yl)ethanone (purchased from Fisher Scientific). 1H-NMR δ 9.41 (bs, 1H), 8.33 (s, 1H), 7.82 (m, 1H), 7.66 (d, 1H), 7.47 (d, 1H), 7.25 (m, 3H), 7.00 (t, 1H), 6.84 (d, 1H), 5.89 (bs, 1H), 3.71 (t, 2H), 3.49 (d, 1H), 3.21 (d, 1H), 1.62 (m, 2H), 1.54 (m, 1H), 0.94 (dd, 6H).
Reaction SMILES: O[CH:2]1[CH2:6][CH2:5][C:4]([CH2:7][CH2:8][CH2:9][CH2:10][PH:11](=[O:15])[O:12][CH2:13][CH3:14])=[CH:3]1.CCOC(/[N:21]=N/C(OCC)=O)=O.N=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1C=CC=CC=1.C1COCC1.O>[NH2:21][CH:2]1[CH2:6][CH2:5][C:4]([CH2:7][CH2:8][CH2:9][CH2:10][PH:11](=[O:15])[O:12][CH2:13][CH3:14])=[CH:3]1
Reactant: CCOC(=O)/N=N/C(=O)OCC
Reactant: CCO[PH](=O)CCCCC1=CC(O)CC1
Agent: [N-]=[N+]=N
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: C1CCOC1
Solvent: c1ccccc1
Product: CCO[PH](=O)CCCCC1=CC(N)CC1
Temperature: 25 °C
Reaction time: 12 h
Yield: 95 %

Procedure:
To a solution of (±)-ethyl (3-hydroxycyclopentenyl)butylphosphinate (7) (2.98 g, 12.8 mmol), DEAD (4.2 cm3) and HN3 (13.5 cm3 of a 1.9 M solution in benzene) in anhydrous THF (150 cm3) at 0° C. was added triphenylphosphine (13.43 g, 51.4 mmol) in small portions over a period of 1 hour. The reaction mixture was allowed to warm to room temperature and stirring continued for 12 hours. The reaction mixture was then heated to 50° C. for 3 hours after which time then water (2 cm3) was added and heating continued for a further 2 hours. The reaction mixture was cooled to room temperature and the solvent removed in vacuo. The residue was partitioned between aqueous HCl (1 M, 40 cm3) and DCM (40 cm3). The organic layer was separated and further extracted with water (3×30 cm3). The combined aqueous fractions were washed with DCM (2×30 cm3) and concentrated in vacuo. The crude product was purified by ion exchange chromatography (Dowex 50, H+), eluting first with water until the eluate was colourless and the pH 7. On further elution with aqueous ammonium hydroxide (1 M), ninhydrin positive fractions were collected and combined and the solvent was removed in vacuo. Recrystallisation from ethanol/acetone followed by drying gave the desired title compound (12) as a pale yellow oil (2.82 g, 95%): 1H-NMR (300 MHz, CDCl3) δH 0.88 (3H, 2×d, J=6.9 and 7.5 Hz, PCH2CH2CH2CH3),0.91 (3H, 2×d, J=7.2 and 7.2 Hz, PCH2CH2CH2CH3), 1.21-1.98 (9H, m, POCH2CH3, PCH2CH2CH2CH3, PCH2CH2CH2CH3,PCH2CH2CH2CH3), 2.38-2.71 (4H, m, C(4)—H, C(4)—H′, C(5)—H and C(5)—H′), 3.87-4.31 (5H, m, POCH2CH3, C(3)—NH2, C(3)—H), 6.51 (1H, d, J=9.6 Hz, C(2)—H); 13C-NMR (75 MHz, CDCl3) δC 13.43 (s, PCH2CH2CH2CH3),16.39 and 16.47 (d, 3JPOCC=6.00 Hz, POCH2CH3), 23.41 and 23.46 (2×d, 2JPC=3.38 and 3.75 Hz, PCH2CH2CH2CH3), 23.63 and 23.84 (d, 3JPC=15.90 Hz, PCH2CH2CH2CH3),27.15 and 28.47 (2×d, JPC=99.0 and 99.0 Hz, PCH2CH2CH2CH3), 31.93 and 32.09 (2×d, 3JPC=11.63 and 11.70 Hz, C(4)), 34.93 and 35.04 (2×d, 2JPC=8.25 and 8.55 Hz, C(5)), 58.86 and 59.09 (2×d, 3JPC=17.03 and 17.33 Hz, C(3)), 60.11 and 60.19 (d, 2JPOC=6.23 Hz, POCH2CH3), 135.63 and 137.72 (d, JPC=156.75 Hz, C(1)), 150.47 and 150.66 (2×d, 2JPC=13.88 and 13.95 Hz, C(2)); 31P-NMR (121 MHz, CDCl3) δP 43.18 and 43.28; MS (CI, CH4) m/z 232.0 (16%) (MH+), 215.1 (100), 446.0 (18), 260.2 (14). Synthesis of (±)-ethyl [3-(t-butyloxycarbonyl)aminocyclopentenyl]butylphosphinate (13)
Reaction SMILES: [F:1][CH2:2][C:3]([NH:5][C:6]1[C:7]([N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[N:8][CH:9]=[CH:10][CH:11]=1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[F:1][CH2:2][CH2:3][NH:5][C:6]1[C:7]([N:12]2[CH2:13][CH2:14][NH:15][CH2:16][CH2:17]2)=[N:8][CH:9]=[CH:10][CH:11]=1
Reactant: O=C(CF)Nc1cccnc1N1CCNCC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: FCCNc1cccnc1N1CCNCC1

Procedure:
Following the general procedure of PREPARATION 36 and making non-critical variations but starting with 1-[3-(2-fluoroacetamido)-2-pyridinyl]- piperazine (PREPARATION 37, 1.4 g), lithium aluminum hydride (11.76 ml, 1M in tetrahydrofuran), the title compound is obtained.
Reaction SMILES: [H-].[Na+].[CH3:3][CH:4]([CH3:16])[C@H:5]([N:8]=CC1C=CC=CC=1)[CH2:6][OH:7].[CH2:17](Br)[CH:18]=[CH2:19].CO>C1COCC1>[CH2:19]([O:7][CH2:6][C@@H:5]([NH2:8])[CH:4]([CH3:3])[CH3:16])[CH:18]=[CH2:17]
Reactant: CC(C)[C@@H](CO)N=Cc1ccccc1
Reactant: C=CCBr
Agent: [H-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: C=CCOC[C@@H](N)C(C)C
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 69.5 %

Procedure:
1.25 g (60%, 31.36 mmol) of sodium hydride were added to a solution of 3.00 g (15.68 mmol) of (S)-3-methyl-2-{[1-phenylmethylidene]amino}butan-1-ol in 28 ml of dry THF, and the mixture was stirred at RT for 45 min. Then 1.43 ml (16.46 mmol) of allyl bromide were added, and the mixture was stirred further at RT overnight. 20 ml of methanol were added to quench, and the mixture was acidified (pH 1) with 1N hydrochoric acid and stirred further. After 3 h, the reaction mixture was washed twice with dichloromethane, and the combined dichloromethane phases were extracted with 1N hydrochloric acid. The combined aqueous phases were basified with 1N sodium hydroxide solution (pH 14), saturated with sodium chloride and extracted three times with ethyl acetate, readjusting the pH after each extraction step. The combined organic phases were dried over sodium sulfate, filtered and concentrated, and taken up once in dichloromethane and again concentrated. 1.56 g of the title compound were obtained as a pale yellow liquid.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:15]#[N:16].[Cl:17][C:18]1[CH:19]=[C:20]([CH:22]=[CH:23][C:24]=1[Cl:25])[NH2:21]>C(O)C>[Cl:17][C:18]1[CH:19]=[C:20]([NH:21][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=3)[N:5]=[CH:4][C:3]=2[C:15]#[N:16])[CH:22]=[CH:23][C:24]=1[Cl:25]
Reactant: Nc1ccc(Cl)c(Cl)c1
Reactant: N#Cc1cnc2ccc([N+](=O)[O-])cc2c1Cl
Solvent: CCO
Product: N#Cc1cnc2ccc([N+](=O)[O-])cc2c1Nc1ccc(Cl)c(Cl)c1
Reaction time: 3.5 h
Yield: 27.3 %

Procedure:
A mixture of 5.00 g (21.5 mmol) 4chloro-6-nitro-3quinolinecarbonitrile, 250 ml ethanol, and 4.17 g (25.6 mmol) 3,4-dichloroaniline was heated to reflux under N2. At 3.5 hours, removed head and made basic with saturated sodium bicarbonate. Stripped solvents and azeotroped with ethanol. Slurried residue with hexane, collected solids and washed with water. Dissolved in ethyl acetate, stirred with Darco, filtered, stripped solvent and dried in vacuo, giving 2.106 g of yellow solid: mass spectrum (electrospray m/e): M+H=359.1, 361.0.