Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:28][CH:29]=O)[CH:9]([C:13]2[CH:27]=[CH:26][C:16]([C:17]([NH:19][CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[O:18])=[CH:15][CH:14]=2)[CH2:10][CH2:11][CH3:12])=[CH:4][CH:3]=1.Cl.[F:32][C:33]1[CH:38]=[C:37]([CH3:39])[CH:36]=[CH:35][C:34]=1[NH:40]N>[Cl-].[Cl-].[Zn+2].C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C:28]2[C:35]3[C:34](=[C:33]([F:32])[CH:38]=[C:37]([CH3:39])[CH:36]=3)[NH:40][CH:29]=2)[C@@H:9]([C:13]2[CH:14]=[CH:15][C:16]([C:17]([NH:19][CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[O:18])=[CH:26][CH:27]=2)[CH2:10][CH2:11][CH3:12])=[CH:4][CH:3]=1
Reactant: Cc1ccc(NN)c(F)c1
Reactant: CCCC(c1ccc(C(=O)NCCC(=O)OC)cc1)C(CC=O)c1ccc(Cl)cc1
Agent: Cl
Agent: [Cl-]
Agent: [Zn+2]
Solvent: CC(=O)O
Product: CCC[C@H](c1ccc(C(=O)NCCC(=O)OC)cc1)[C@H](c1ccc(Cl)cc1)c1c[nH]c2c(F)cc(C)cc12

Procedure:
An acetic acid solution (10 ml) of methyl N-{4-[2-(4-chlorophenyl)-4-oxo-1-propylbutyl]benzoyl}-β-alaninate, INTERMEDIATE 4, (757 mg, 1.76 mmol), ZnCl2 (3.1M in AcOH, 1.7 ml, 5.27 mol) and 2-fluoro-4-methylphenylhydrazine hydrochloride (374 mg, 2.1 mmol) was heated at 80° C. for 45 minutes. The solution was concentrated and the residue partitioned between EtOAc and water. The organic phase was washed with water (2×), brine (2×) and dried over Na2SO4. The solution was filtered, concentrated and the residue purified by silica gel chromatography using a hexanes/ethyl acetate gradient to give the title compound. Data for the major diastereomer: 1H NMR (500 MHz, CD3CN): δ 9.11 (s, 1 H); 7.54 (d, J=8.2 Hz, 2 H); 7.48 (d, J=8.5 Hz, 2H); 7.38 (d, J=8.2 Hz, 2 H); 7.30 (d, J=8.4 Hz, 2 H); 7.15 (d, J=2.5 Hz, 1 H); 7.11 (s, 1 H); 7.02-6.97 (m, 1 H); 6.59 (d, J=12.3 Hz, 1 H); 4.49 (d, J=11.6 Hz, 1 H); 3.60 (s, 3H); 3.56-3.48 (m, 3 H); 2.52 (t, J=6.8 Hz, 2 H); 2.32 (s, 3 H); 1.49-1.35 (m, 2 H); 1.04-0.90 (m, 2 H); 0.69 (t, J=7.4 Hz, 3 H). LC1=3.94 min. (M+H)=535. Chiral LC1 (1% to 15% EtOH/heptane over 25 min, 15% EtOH/heptane isocratic >25 min) retention time=28.38 minutes. The material also contains ca 2% by area of the enantiomer. Chiral LC1 (1% to 15% EtOH/heptane over 25 min, 15% EtOH/heptane isocratic >25 min) retention time=26.88 minutes.
Reaction SMILES: [NH2:1][CH:2]([CH:8]([OH:26])[CH2:9][CH2:10][CH:11]([NH:17][C:18](=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:3]([O:5][CH2:6][CH3:7])=[O:4].CCN(CC)CC.[C:34](Cl)(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>C(Cl)Cl>[C:34]([NH:1][CH:2]([CH:8]([OH:26])[CH2:9][CH2:10][CH:11]([NH:17][C:18](=[O:25])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:3]([O:5][CH2:6][CH3:7])=[O:4])(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: CCOC(=O)C(CCC(O)C(N)C(=O)OCC)NC(=O)c1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)C(CCC(O)C(NC(=O)c1ccccc1)C(=O)OCC)NC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 59 %

Procedure:
Amine (9) (4.0 g, 10.9 mM) is taken up in CH2Cl2 (150 ml), cooled in an ice bath, and treated with Et3N (1.67 ml, 12 mM). Benzoyl chloride (1.27 ml, 10.9 mM) is added slowly over a period of 5 minutes and stirring continued at 4° C. for 1 hour. The reaction is warmed to room temperature and stirred overnight. This mixture is washed with 5% aqueous HCl (3×100 ml), saturated aqueous NaCl (3×100 ml), dried over anhydrous MgSO4, filtered and evaporated to dryness in vacuo to yield a white foam. The latter is purified by flash chromatography on silica gel eluting with 12% acetone/CH2Cl2 to yield 3.0 g (59% yield) of the desired product as a white foam. 'H-N.M.R. (CDCl3 /TMS): δ=1.19 (t, 3H, --CH2CH3); 1.22 (t, 3H, --CH2CH3); 1.40-2.27 (m, 4H, --CH2CH2 --); 4.19 (2q, 4H, --CH2CH3); 4.00-5.00 (4H, 10H, 2>CHCO2Et, CHOH); 6.90-7.86 ppm (m, 12H, 2NH and 2Ph).
Reaction SMILES: C[Si](C)(C)[O:3][C:4]([CH:6]=[CH2:7])=[CH2:5].[C:10]([O:15][CH2:16][CH:17]([CH3:19])[CH3:18])(=[O:14])[C:11]([CH3:13])=[CH2:12].F[P-](F)(F)(F)(F)F.C([N+]1C=CN(C)C=1)CCC>C(C1C=C(C(C)(C)C)C(O)=C(C(C)(C)C)C=1)C1C=C(C(C)(C)C)C(O)=C(C(C)(C)C)C=1>[CH3:12][C:11]1([C:10]([O:15][CH2:16][CH:17]([CH3:19])[CH3:18])=[O:14])[CH2:7][CH2:6][C:4](=[O:5])[CH2:3][CH2:13]1
Reactant: C=CC(=C)O[Si](C)(C)C
Reactant: C=C(C)C(=O)OCC(C)C
Agent: CC(C)(C)c1cc(Cc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)cc(C(C)(C)C)c1O
Agent: CCCC[n+]1ccn(C)c1
Agent: F[P-](F)(F)(F)(F)F
Product: CC(C)COC(=O)C1(C)CCC(=O)CC1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 21.4 %

Procedure:
2-(Trimethylsilyloxy)buta-1,3-diene (40 g, 281 mmol) was weighed into a Teflon™ microwave container. Isobutyl methacrylate (50.8 mL, 317 mmol) was added followed by 4,4′-methylenebis(2,6-di-tert-butylphenol) (0.5 g, 1.177 mmol), finally 1-butyl-3-methylimidazolium hexafluorophosphate (0.5 mL) was added, the vessel transferred to the Advancer microwave and heated for 4 hr (normal absorption, no fixed hold time, 190° C.). After 1 hr 20 min an error message was seen for the temperature probe, the error was cleared and heating was continued for a further hour. At this time the software had frozen forcing a shutdown at the mains. The reaction mixture was allowed to cool to RT. Tetrahydrofuran (THF) (200 mL) was added and the solution transferred to a round bottomed flask. 2M HCl was added and the reaction mixture left to stir overnight. DCM was added to the reaction mixture, whereupon an emulsion formed. An attempt to filter this was unsuccessful, and the mixture was left to stand overnight. The organic layer was separated, dried (Na2SO4) and evaporated to give a sticky oil. Flash column chromatography, eluting with ethyl acetate/isohexane gave 2-methylpropyl 1-methyl-4-oxocyclohexanecarboxylate as a yellow oil (12.74 g, 60.0 mmol, 21.35% yield).
Reaction SMILES: [CH2:1]([N:3]1[C:12](=[O:13])[C:11]2[N:10]([CH3:14])[C:9](/[CH:15]=[CH:16]/[C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=3)=[N:8][C:7]=2[N:6]([CH2:24][CH3:25])[C:4]1=[O:5])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH2:32](Br)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.O>CN(C)C=O>[CH2:32]([O:23][C:20]1[CH:19]=[CH:18][C:17](/[CH:16]=[CH:15]/[C:9]2[N:10]([CH3:14])[C:11]3[C:12](=[O:13])[N:3]([CH2:1][CH3:2])[C:4](=[O:5])[N:6]([CH2:24][CH3:25])[C:7]=3[N:8]=2)=[CH:22][CH:21]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: BrCc1ccccc1
Reactant: CCn1c(=O)c2c(nc(/C=C/c3ccc(O)cc3)n2C)n(CC)c1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCn1c(=O)c2c(nc(/C=C/c3ccc(OCc4ccccc4)cc3)n2C)n(CC)c1=O
Temperature: 80 °C
Reaction time: 2.5 h
Yield: 53.7 %

Procedure:
Compound 175 (100 mg, 0.29 mmol) obtained in Reference Example 114 was dissolved in 2 ml of dimethylformamide. To the solution were added 162 mg (1.17 mmol) of potassium carbonate and 0.28 ml (2.35 mmol) of benzyl bromide, and the mixture was stirred at 80° C. for 2.5 hours. Water was added thereto under ice cooling to dissolve potassium carbonate and the deposited crystals were collected by filtration. The collected crude crystals were dissolved in chloroform, washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, followed by evaporation under reduced pressure. The residue was recrystallized from hexane/ethyl acetate to give 67 mg (yield 53%) of Compound 176 as yellow needles.
Reaction SMILES: [C:1]([O:5][C:6](=[O:22])[CH2:7][NH:8][CH:9]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:23]CN(C(C)C)C(C)C.CCOCC.[CH3:37][C:38]([CH3:40])=[O:39]>>[C:1]([O:5][C:6](=[O:22])[CH2:7][N:8]([CH:9]([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[CH2:37][C:38](=[O:39])[CH2:40][CH3:23])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)CNC(c1ccccc1)c1ccccc1
Reactant: CCN(C(C)C)C(C)C
Reactant: CC(C)=O
Solvent: CCOCC
Product: CCC(=O)CN(CC(=O)OC(C)(C)C)C(c1ccccc1)c1ccccc1
Temperature: 25 °C
Yield: 98 %

Procedure:
To a solution of (benzhydrylamino)acetic acid tert-buyl ester (6.1 g, 20.5 mmol, 1 eq.) in dry acetone (75 mL) at −50° C. to −60° C. was added DIEA (3.58 mL, 20.5 mmol, 1 eq.) followed by a solution of 1-bromobuta-2-none (2.33 mL, 20.5 mmol, 1 eq.) in acetone (75 mL). The reaction mixture was allowed to warm to room temperature and then heated to reflux for 2 h. The reaction was cooled and then added additional 5% (by weight) of DIEA and 1-bromobuta-2-none. The resulting mixture was continued to be heated at reflux overnight. The reaction mixture was cooled to room temperature and added Et2O. The precipitated solid was filtered off and washed with Et2O. The combined organic layer was washed with brine, dried over MgSO4, filtered, and concentrated in vacuo to afford [benzhydryl-(2-oxobutyl)amino]acetic acid tert-butyl ester in 98% yield (crude product), which was used without further purification. ESMS: m/z 368.4 [M+H].
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].[CH2:7]([NH2:15])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[ClH:16]>>[Cl-:16].[CH2:7]([NH3+:15])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCCCCN
Reactant: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CCCCCCCC[NH3+]
Product: [Cl-]
Reaction time: 12 h

Procedure:
K2CO3, ZnO and TiO2 were thoroughly ground to form a homogeneous mixture having the stoichiometric K0.80 (Zn0.40 Ti1.60)O4 which was then fired in air in a ceramic crucible at 900° C. for 200 minutes and then at 1050° C. for 720 minutes. The product was then reground and refired under the same conditions. The resulting stiff powder was then ground to about 100 mesh to yield a product analysed as K0.66 (Zn0.35 Ti1.49)O4. The d-layer spacing from X-ray powder diffraction d(A) was measured as 7.83. Excess octylamine (5 mole equiv/mole equiv of titanozincate) was slowly added to a solution of 12% HCl (4.9 equiv HCl/mole) while keeping the temperature of the reaction mixture below 50° C. to form an acidic aqueous octylammonium chloride solution. The titanozincate was then added to the chloride solution and the mixture was heated to reflux for 24 hours. The reaction mixture was cooled, filtered and washed with hot distilled water. The air dried product was a material having the composition
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]([C:9]2[CH:10]=[C:11]([NH:15][C:16]([NH:18]C(=O)C3C=CC=CC=3)=[S:17])[CH:12]=[CH:13][CH:14]=2)[CH:4]=1.[OH-].[Na+].Cl>CO.O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]([C:9]2[CH:10]=[C:11]([NH:15][C:16]([NH2:18])=[S:17])[CH:12]=[CH:13][CH:14]=2)[CH:4]=1
Reactant: COc1ccnc(-c2cccc(NC(=S)NC(=O)c3ccccc3)c2)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COc1ccnc(-c2cccc(NC(N)=S)c2)c1
Temperature: 60 °C
Reaction time: 1 h
Yield: 96 %

Procedure:
To a suspension of N-(3-(4-methoxypyridin-2-yl)phenyl)-N′-benzoylthiourea (429 mg) in methanol (5 ml) was added an aqueous sodium hydroxide solution (1N, 1.42 ml) dropwise. The mixture was stirred at 60° C. for 1 hour and cooled to ambient temperature. The pH was adjusted to 8.0 with 1N hydrochloric acid. The mixture was diluted with water (50 ml) and extracted with dichloromethane-methanol (4:1). The organic layer was washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was triturated with diisopropyl ether, collected by filtration, washed with diisopropyl ether and dried under reduced pressure to give N-(3-(4-methoxypyridin-2-yl)phenyl)thiourea (294 mg).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][S:9]([N:12]([CH3:14])[CH3:13])(=[O:11])=[O:10])[CH:5]=[CH:6][CH:7]=1.Cl[C:16]1[CH:21]=[C:20]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=2[O:29][CH3:30])[CH:19]=[CH:18][N:17]=1>>[F:28][C:25]1[CH:26]=[CH:27][C:22]([C:20]2[CH:21]=[CH:16][N:17]=[C:18]([NH:1][C:2]3[CH:3]=[C:4]([CH2:8][S:9]([N:12]([CH3:14])[CH3:13])(=[O:11])=[O:10])[CH:5]=[CH:6][CH:7]=3)[CH:19]=2)=[C:23]([O:29][CH3:30])[CH:24]=1
Reactant: CN(C)S(=O)(=O)Cc1cccc(N)c1
Reactant: COc1cc(F)ccc1-c1ccnc(Cl)c1
Product: COc1cc(F)ccc1-c1ccnc(Nc2cccc(CS(=O)(=O)N(C)C)c2)c1
Temperature: 140 °C

Procedure:
The title compound G3 was prepared from 1-(3-aminophenyl)-N,N-dimethylmethanesulfonamide (400 mg, 1.87 mmol) and intermediate A2 (532 mg, 2.24 mmol) following the procedure reported for G1 by heating the reaction mixture for 2 h at 140° C. in a microwave oven. The desired product G3 was obtained by flash chromatography on silica gel (cHex/EtOAc 80:20 to 20:80) as a white solid (274 mg, 35%). 1H NMR (400 MHz, d6-DMSO, 300K) δ 2.71 (s, 6H), 3.81 (s, 3H), 4.34 (s, 2H), 6.82 (dd, J=5.3 Hz, J=1.5 Hz, 1H), 6.88 (dt, J=8.3 Hz, J=1.5 Hz, 1H), 6.91 (d, J=8.0 Hz, 1H), 6.95 (s, 1H), 7.05 (dd, J=11.4 Hz, J=2.4 Hz, 1H), 7.25 (t, J=7.8 Hz, 1H), 7.38 (dd, J=8.3 Hz, J=7.0 Hz, 1H), 7.67 (s, 1H), 7.72 (d, J=8.3 Hz, 1H), 8.14 (d, J=5.3 Hz, 1H), 9.11 (s, 1H). MS (ES) C21H22FN3O3S requires: 415. found: 416 (M+H)+.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][C:4]1[C:9](=[O:10])[N:8]2[CH:11]=[C:12]([O:15][CH3:16])[CH:13]=[CH:14][C:7]2=[N:6][C:5]=1[CH3:17].CC(O)C.Cl.[H][H]>[Pd].CO>[ClH:1].[Cl:1][CH2:2][CH2:3][C:4]1[C:9](=[O:10])[N:8]2[CH2:11][CH:12]([O:15][CH3:16])[CH2:13][CH2:14][C:7]2=[N:6][C:5]=1[CH3:17]
Reactant: [H][H]
Reactant: COc1ccc2nc(C)c(CCCl)c(=O)n2c1
Agent: [Pd]
Agent: Cl
Solvent: CC(C)O
Solvent: CO
Product: COC1CCc2nc(C)c(CCCl)c(=O)n2C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 64 %

Procedure:
A mixture of 10 parts of 3-(2-chloroethyl)-7-methoxy-2-methyl-4H-pyrido[1,2-a]-pyrimidin-4-one, 40 parts of 2-propanol saturated with hydrogen chloride and 160 parts of methanol was hydrogenated at normal pressure and at room temperature with 2.0 parts of palladium-on-charcoal catalyst 10%. After the calculated amount of hydrogen was taken up, the catalyst was filtered off over diatomaceous earth and the filtrate was evaporated. The oily residue was taken up in 80 parts of 2-propanol and 2,2'-oxybispropane. After stirring overnight at room temperature, the precipitated product was filtered off, washed with a mixture of 2-propanol and 2,2'-oxybispropane and dried in vacuo at 50° C., yielding 7.5 parts (64.0%) of 3-(2-chloroethyl)-6,7,8,9-tetrahydro-7-methoxy-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one monohydrochloride; mp. 170° C. (intermediate 4)
Reaction SMILES: [H-].[K+].Br[C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][CH:5]=1.[H][H].[Li]C(C)(C)C.[N:20]12[CH2:28][CH2:27][CH2:26][CH:25]1[CH2:24][C:23](=[O:29])[CH2:22][CH2:21]2>O1CCCC1>[OH:29][C:23]1([C:4]2[CH:12]=[C:11]3[C:7]([CH:8]=[CH:9][NH:10]3)=[CH:6][CH:5]=2)[CH2:24][CH:25]2[N:20]([CH2:28][CH2:27][CH2:26]2)[CH2:21][CH2:22]1
Reactant: O=C1CCN2CCCC2C1
Reactant: [H][H]
Reactant: Brc1ccc2cc[nH]c2c1
Agent: [H-]
Agent: [K+]
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Product: OC1(c2ccc3cc[nH]c3c2)CCN2CCCC2C1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 169 %

Procedure:
To a suspension of potassium hydride (KH; 0.289 g, 7.2 mmol) in tetrahydrofuran (THF; 5 ml) at −10° C. was added, dropwise, a solution of 6-bromoindole (1.2 g, 6 mmol) in THF (1 ml). The mixture was stirred at this temperature for 20 mins, until no more evolution of hydrogen was observed. The mixture was then cooled to −78° C. in an acetone/dry ice bath, 8.82 ml of a 1.7M solution of tBuLi was added slowly, and the mixture stirred for another 30 mins. Azabicyclo[4,3,0]nonan-4-one (1.67 g. 1.2 mmol) was then added, and the mixture stirred at −78° C. for a further 30 mins before being quenched with a mixture of dichloromethane (50 ml) and pH7 buffer (50 ml). After filtration, the organic layer was washed with water and brine, dried, concentrated, and the residue triturated with hexanes to give 0.52 g of the title product as a white powder (33.1%).
Reaction SMILES: [C:1]1([CH:7]=[N+]=[N-])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H][H].[CH:12](=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>ClCCl.C([O-])(=O)C.[Rh+2].C([O-])(=O)C>[C:1]1([C@H:7]2[C@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[O:19]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:1]1([C@H:7]2[C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[O:19]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: [H][H]
Reactant: [N-]=[N+]=Cc1ccccc1
Reactant: O=Cc1ccccc1
Agent: [Rh+2]
Agent: CC(=O)[O-]
Solvent: ClCCl
Product: c1ccc([C@@H]2O[C@H]2c2ccccc2)cc1
Product: c1ccc([C@H]2O[C@H]2c2ccccc2)cc1
Yield: 1.5 %
Yield: 16 %

Procedure:
A solution of phenyldiazomethane (1 mmol in 6 ml of t-butyl methyl ether) was added, over a period of 12 hours, to a solution of a sulphide of formula (C) wherein R' and R" are both hydrogen (for preparation see J. Org. Chem. 44 (20) 3598-9 (1979); 198 mg, 1.0 mmol), rhodium (II) acetate (4 mg, 0.01 mmol) and benzaldehyde (190 μl, 1.0 mmol) in dichloromethane (4 ml). Upon completion of the addition, the solvent was removed in vacuo and the residue chromatographed using silica gel eluting with dichloromethane:petrol 40:60 to yield trans-2,3-diphenyl oxirane (31 mg, 16%, 51%ee) and cis-2 3-diphenyl oxirane (3 mg, 1.5%).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][C:7]([O:11][CH:12]([CH2:16][CH3:17])[C:13]([OH:15])=O)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[NH2:18][C:19]([CH3:32])([CH3:31])[C:20]#[C:21][CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25].Cl.CN(C)CCCN=C=NCC.CCCCCC.C(OCC)(=O)C>CN(C)C1C=CN=CC=1.ClCCl>[N:1]1[C:10]2[C:5](=[CH:6][C:7]([O:11][CH:12]([CH2:16][CH3:17])[C:13]([NH:18][C:19]([CH3:32])([CH3:31])[C:20]#[C:21][CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:25])[CH3:26])=[O:15])=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: CC(C)(N)C#CCO[Si](C)(C)C(C)(C)C
Reactant: CCC(Oc1ccc2ncccc2c1)C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CCCCCC
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CCC(Oc1ccc2ncccc2c1)C(=O)NC(C)(C)C#CCO[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 10.9 %

Procedure:
2-(6-Quinolinyloxy)butyric acid (0.61 g), 4-amino-1-tert-butyldimethylsilyloxy-4-methylpent-2-yne (0.57 g) and 4-dimethylaminopyridine (0.010 g) in dry dichloromethane (10 ml) were stirred and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.53 g) was added. The mixture was stirred at ambient temperature for 3.5 hours, stored for 2 days, diluted with dichloromethane, washed with saturated aqueous sodium hydrogen carbonate (twice) and then with water. The organic phase was dried over magnesium sulphate and evaporated under reduced pressure to give a yellow oil. The oil was fractionated by chromatography (silica; hexane/ethyl acetate, 3:1 by volume) to give a gum that was triturated with hexane to give the required product (0.12 g) as a colourless solid, m.p. 78–80° C.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:6]=[CH:7][CH:8]=1.C(N(CC)CC)C.[N+:24]([C:27]1[CH:28]=[C:29]([CH:33]=[CH:34][CH:35]=1)[C:30](Cl)=[O:31])([O-:26])=[O:25].C([O-])([O-])=O.[Na+].[Na+]>O1CCCC1>[N+:24]([C:27]1[CH:28]=[C:29]([CH:33]=[CH:34][CH:35]=1)[C:30]([NH:1][CH2:2][C:3]1[CH:4]=[C:5]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:15])[CH3:14])[CH:6]=[CH:7][CH:8]=1)=[O:31])([O-:26])=[O:25]
Reactant: O=C(Cl)c1cccc([N+](=O)[O-])c1
Reactant: CC(C)(C)OC(=O)Nc1cccc(CN)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)Nc1cccc(CNC(=O)c2cccc([N+](=O)[O-])c2)c1
Temperature: 25 °C
Yield: 104.7 %

Procedure:
To a stirring solution of tert-butyl [3-(aminomethyl)phenyl]carbamate (2.0 g, 9.0 mmol) and triethylamine (1.3 mL, 9.4 mmol) in dry tetrahydrofuran (25 mL) at 0° C. slowly added a solution of 3-nitrobenzoyl chloride (1.75 g, 9.45 mmol) in tetrahydrofuran (7.3 mL). The resulting mixture was slowly warmed up to rt and stirred for one additional hour at rt. The reaction mixture was treated with Na2CO3 (aq), separated. The aqueous layer was extracted with EtOAc three times. The combined organic layers were dried, filtered and concentrated to give the desired product as an off-white powder (3.5 g, 100%). LCMS for C19H21N3O5 (M-tBu+H)+: m/z=316.0. 1H NMR (400 MHz, CD3OD): δ 8.71 (t, J=2.0 Hz, 1H), 8.38 (ddd, J=8.4, 1.6, 1.2 Hz, 1H), 8.23 (ddd, J=8.0, 1.6, 0.8 Hz, 1H), 7.70 (t, J=8.0 Hz, 1H), 7.44 (s, 1H), 7.28 (m, 1H), 7.20 (t, J=7.6, 1H), 7.00 (d J=7.6 Hz, 1H), 4.90 (s, 2H), 1.49 (s, 9H).
Reaction SMILES: [C:1]([C:4]1[CH:5]=[CH:6][C:7]([O:14][CH3:15])=[C:8]([S:10](Cl)(=[O:12])=[O:11])[CH:9]=1)(=[O:3])[NH2:2].[NH2:16][CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH:25]([CH3:27])[CH3:26])=[CH:21][C:20]=1[S:28]([NH:31][C:32]([CH3:35])([CH3:34])[CH3:33])(=[O:30])=[O:29].C(N(CC)CC)C.Cl>CN(C)C=O.O>[C:32]([NH:31][S:28]([C:20]1[CH:21]=[C:22]([CH:25]([CH3:26])[CH3:27])[CH:23]=[CH:24][C:19]=1[CH2:18][CH2:17][NH:16][S:10]([C:8]1[CH:9]=[C:4]([CH:5]=[CH:6][C:7]=1[O:14][CH3:15])[C:1]([NH2:2])=[O:3])(=[O:12])=[O:11])(=[O:30])=[O:29])([CH3:33])([CH3:34])[CH3:35]
Reactant: COc1ccc(C(N)=O)cc1S(=O)(=O)Cl
Reactant: CC(C)c1ccc(CCN)c(S(=O)(=O)NC(C)(C)C)c1
Agent: Cl
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COc1ccc(C(N)=O)cc1S(=O)(=O)NCCc1ccc(C(C)C)cc1S(=O)(=O)NC(C)(C)C
Temperature: 25 °C
Reaction time: 72 h
Yield: 86.3 %

Procedure:
To a suspension of 241 mg of 5-carbamoyl-2-methoxybenzenesulfonyl chloride and 288 mg of 2-(2-aminoethyl)-N-tert-butyl-5-isopropylbenzenesulfonamide in 10 mL of N,N-dimethylformamide was added 0.32 mL of triethylamine, and the mixture was stirred at room temperature for 3 days. To the reaction mixture was added 30 mL of water, and the mixture was stirred at the same temperature for 1 hour. To the mixture was added 10 mL of 1 mol/L hydrochloric acid, and the mixture was extracted three times with 20 mL of ethyl acetate. The organic layers were combined and washed with 30 mL of water, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give 426 mg of 3-[[2-(2-tert-butylsulfamoyl-4-isopropylpheyl)ethyl]sulfamoyl]-4-methoxybenzamide.
Reaction SMILES: [OH:1][C:2]1[C:7]2[C:8]3[CH2:9][NH:10][CH2:11][CH2:12][C:13]=3[C:14]([CH3:17])([CH3:16])[O:15][C:6]=2[CH:5]=[C:4]([C:18]([CH3:26])([CH3:25])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH:3]=1.Cl[CH2:28][C:29]([NH:31][C:32]([NH2:34])=[O:33])=[O:30]>>[OH:1][C:2]1[C:7]2[C:8]3[CH2:9][N:10]([CH2:28][C:29]([NH:31][C:32]([NH2:34])=[O:33])=[O:30])[CH2:11][CH2:12][C:13]=3[C:14]([CH3:16])([CH3:17])[O:15][C:6]=2[CH:5]=[C:4]([C:18]([CH3:25])([CH3:26])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH:3]=1
Reactant: CCCCCCC(C)(C)c1cc(O)c2c(c1)OC(C)(C)C1=C2CNCC1
Reactant: NC(=O)NC(=O)CCl
Product: CCCCCCC(C)(C)c1cc(O)c2c(c1)OC(C)(C)C1=C2CN(CC(=O)NC(N)=O)CC1

Procedure:
The above-titled compound was prepared by reacting 10-hydroxy-5,5-dimethyl-8-(1,1-dimethylheptyl)-1,2,3,4-tetrahydro-5H-[1]benzopyrano[4,3-c]pyridine with chloroacetyl-urea according to the method of Example 2.