Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CS(O[C@H:6]([CH3:16])[CH2:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[CH3:15])(=O)=O.[N-:17]=[N+:18]=[N-:19].[Na+].O>CN(C=O)C>[N:17]([C@@H:6]([CH3:16])[CH2:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[CH3:15])=[N+:18]=[N-:19]
Reactant: [N-]=[N+]=[N-]
Reactant: Cc1ccc(F)cc1C[C@@H](C)OS(C)(=O)=O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc(F)cc1C[C@H](C)N=[N+]=[N-]
Temperature: 80 °C
Reaction time: 2 h
Yield: 30 %

Procedure:
A solution of (R)-1-(5-fluoro-2-methylphenyl)propan-2-yl methanesulfonate (6.3 g, 2.56 mmol) in anhydrous DMF (30 mL) was added sodium azide (3.32 g, 5.11 mmol) and the solution was heated to 80° C. and stirred for 2 h. Then, the temperature was cooled to rt and 20 mL of water was added, extracted with EtOAc/hexane (1/1, v/v), dried over anhydrous MgSO4 and evaporated to give crude oil, which was passed through silicagel pad and evaporated under reduced pressure to give (S)-2-(2-azidopropyl)-4-fluoro-1-methylbenzene (F-3), which used as starting material for next reduction without more purification. To the solution of (S)-2-(2-azidopropyl)-4-fluoro-1-methylbenzene in 80 mL of EtOAc was added Pd/C (500 mg, 10% Pd) and the mixture was hydrogenated under Parr Apparatus (30˜40 psi) for 2 h. The catalyst was removed by filtration through Celite pad, then purified by column chromatography as an eluent (EtOAc/MeOH/NH4OH=93/5/2) to give (S)-1-(5-fluoro-2-methylphenyl)propan-2-amine (F) as pale yellow oil (total yield=30% through 4 steps). MS (ESI) m/z 168.0 [M+H]+; 1H NMR (CDCl3, 500 MHz) δ 7.10 (m, 1H), 6.84 (m, 2H), 3.19 (m, 1H), 2.69 (dd, J=13.5, 6.0 Hz, 1H), 2.56 (dd, J=13.5, 8.0 Hz, 1H), 2.28 (s, 3H), 1.68 (bs, 2H), 1.15 (d, J=6.0 Hz, 3H).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].[Cl-].[Mg+2].[Cl-].[CH2:12]=[O:13].C(N(CC)CC)C.Cl>C(#N)C>[Br:1][C:2]1[C:3]([OH:8])=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH:12]=[O:13]
Reactant: Oc1ccccc1Br
Reactant: C=O
Agent: Cl
Agent: [Cl-]
Agent: [Mg+2]
Solvent: CCN(CC)CC
Solvent: CC#N
Product: O=Cc1cccc(Br)c1O
Temperature: 0 °C

Procedure:
20.0 g (115.6 mmol) of 2-bromophenol are introduced into 500 ml of dry acetonitrile. 16.84 g (176.87 mmol) of dry magnesium chloride, 23.4 g of paraformaldehyde granules and 41.9 ml (300.6 mmol) of triethylamine are added. The reaction mixture is heated under reflux for 4 h and, after cooling to 0° C., 300 ml of 2N hydrochloric acid are added. The aqueous phase is extracted three times with 200 ml of diethyl ether each time. The organic phase is dried over magnesium sulphate, and the solvent is removed in vacuo. 24 g (64% of theory, 62% pure according to HPLC) of the title compound are isolated and reacted further without further purification.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][C:9]2=[O:12])=[CH:4][CH:3]=1.[I-].[Na+].[H-].[Na+].[I-].Cl[CH2:19][CH2:20][S+](C)C>C(O)(C)(C)C.O>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][C:8]3([CH2:20][CH2:19]3)[C:9]2=[O:12])=[CH:4][CH:3]=1
Reactant: C[S+](C)CCCl
Reactant: O=C1CCCc2ccc(Br)cc21
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)(C)O
Product: O=C1c2cc(Br)ccc2CCC12CC2
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 72.1 %

Procedure:
To a solution of 7-bromo-1-tetralone (1.03 g, 4.58 mmol) in tert-butanol (10 mL) was added sodium iodide (0.131 g, 0.872 mmol) and sodium hydride (0.349 g, 60% suspension in mineral oil, 8.72 mmol). The reaction mixture was stirred at r.t. for 20 min. Then (2-chloroethyl)dimethylsulfonium iodide (Intermediate 5, 1.10 g, 4.36 mmol) was added portionwise over 1 h. After the reaction had reached completion, water (15 mL) was added and the resulting mixture was extracted with EtOAc (3×15 mL). The combined organic layers were dried with sodium sulfate, filtered and concentrated in vacuo. The product was purified by flash chromatography using 5% EtOAc in heptanes as eluent to give the title compound (0.789 g, 78%). 1H NMR (400 MHz, CDCl3) δ ppm 0.84 (dd, 2 H), 1.40 (dd, 2 H), 1.95 (t, 2 H), 2.93 (t, 2 H), 7.14 (d, 1 H), 7.55 (dd, 1 H), 8.11 (d, 1 H); MS (ES+) m/z 250.98, 253.03 [M+H]+.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1/[CH:6]=[CH:7]/[CH:8]([N:25]([OH:28])[CH:26]=[O:27])[CH2:9][S:10]([N:13]1[CH2:22][CH2:21][C:20]2[C:15](=[CH:16][C:17]([O:23][CH3:24])=[CH:18][CH:19]=2)[CH2:14]1)(=[O:12])=[O:11].[H][H]>CO.[Pd]>[OH:28][N:25]([CH:8]([CH2:9][S:10]([N:13]1[CH2:22][CH2:21][C:20]2[C:15](=[CH:16][C:17]([O:23][CH3:24])=[CH:18][CH:19]=2)[CH2:14]1)(=[O:11])=[O:12])[CH2:7][CH2:6][CH:2]1[CH2:3][CH2:4][CH2:5][O:1]1)[CH:26]=[O:27]
Reactant: [H][H]
Reactant: COc1ccc2c(c1)CN(S(=O)(=O)CC(/C=C/c1ccco1)N(O)C=O)CC2
Agent: [Pd]
Solvent: CO
Product: COc1ccc2c(c1)CN(S(=O)(=O)CC(CCC1CCCO1)N(O)C=O)CC2
Yield: 33.2 %

Procedure:
A solution of N-((2E)-3-(2-furyl)-1-{[(7-methoxy-3,4-dihydroisoquinolin-2(1H)-yl)sulfonyl]methyl}prop-2-en-1-yl)-N-hydroxyformamide (30 mg, 0.073 mmol) in MeOH (3 ml) was hydrogenated over 10% Pd/C under 5 bars of hydrogen for 2 hours. The reaction mixture was filtered and the solvent was evaporated under reduced pressure to give the title compound (33) as a colorless oil (10 mg, 33%). HPLC, Rt: 3.2 min (purity: 84.3%). LC/MS, M+(ESI): 413.3, M−(ESI): 411.2.
Reaction SMILES: [Na].[SH:2][CH:3]([CH2:6][SH:7])[CH2:4][OH:5].Cl[CH2:9][C:10]([CH2:12]Cl)=[CH2:11]>C(O)C>[OH:5][CH2:4][CH:3]1[CH2:6][S:7][CH2:12][C:10](=[CH2:9])[CH2:11][S:2]1
Reactant: C=C(CCl)CCl
Reactant: OCC(S)CS
Agent: [Na]
Solvent: CCO
Product: C=C1CSCC(CO)SC1
Yield: 92.2 %

Procedure:
Sodium metal (0.77 g) was dissolved in 35 mL of absolute ethanol at room temperature under nitrogen protection. Then 2,3-dimercapto-1-propanol (1.99 g, 1.6 mL, 16 mmoles) was added dropwise. The solution was taken up in a syringe and diluted to 44 mL. Solution 2. 2-(Chloromethyl)-3-chloro-1-propene (2 g, 16 mmoles) was dissolved in 30 mL of absolute ethanol. The solution was taken up into a syringe and diluted to a volume of 44 mL. Solutions 1 and 2 were added simultaneously (via syringe pump using separate teflon feed lines) to a 40 mL of absolute ethanol at room temperature under nitrogen protection over a period of one hour. After the addition was completed, the reaction was refluxed for one hour. The reaction was then worked up by evaporation of the solvent, dilution with water and extraction with ether. The ether extracts were dried and evaporated to give 2.6 g of oil. The oil was chromatographed on Silica gel using ether:hexane (1:3) to give 1.6 g (57%) of clear oil.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=3)=[CH:14][CH:15]=2)[C:10]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[C:9]1[CH3:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:39][C:40]#[N:41]>CC(C)=O>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH2:39][C:40]#[N:41])=[CH:19][CH:18]=3)=[CH:14][CH:15]=2)[C:10]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[C:9]1[CH3:31])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: N#CCBr
Reactant: Cc1c(Cc2ccccc2)c2cc(-c3ccc(O)cc3)ccc2n1Cc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: Cc1c(Cc2ccccc2)c2cc(-c3ccc(OCC#N)cc3)ccc2n1Cc1ccccc1

Procedure:
The desired product was prepared using a procedure similar to step 5 of example 3. Thus, 4-(1,3-dibenzyl-2-methyl-1H-indol-5-yl)-phenol (0.164 g, 0.406 mmol) was reacted with K2CO3 (0.073 g, 0.528 mmol) and bromoacetonitrile (0.063 g, 0.528 mmol) in acetone (5 ml) to give the product (0.164 g, 0.371 mmol, 91%) as a pale-yellow, viscous oil. 1H NMR (DMSO-d6) a 2.35 (s, 3H), 4.11 (s, 2H), 5.18 (s, 2H), 5.43 (s, 2H), 6.99 (d, J=7.2 Hz, 2H), 7.09-7.13 (m, 3H), 7.20-7.26 (m, 5H), 7.27-7.30 (m, 3H), 7.41 (d, J=8.4 Hz, 1H), 7.56-7.59 (m, 2H), 7.62 (d, J=1.7 Hz, 1H); [ESI(+)], m/z 443 (M+H)+.
Reaction SMILES: ClCl.[CH3:3][S:4][CH3:5].[C:6]12([O:16][C:17]3[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][CH:18]=3)[CH2:15][CH:10]3[CH2:11][CH:12]([CH2:14][CH:8]([CH2:9]3)[CH2:7]1)[CH2:13]2.C(N(CC)CC)C>C(Cl)Cl>[C:6]12([O:16][C:17]3[CH:18]=[CH:19][C:20]([NH2:21])=[C:22]([CH2:3][S:4][CH3:5])[CH:23]=3)[CH2:13][CH:12]3[CH2:11][CH:10]([CH2:9][CH:8]([CH2:14]3)[CH2:7]1)[CH2:15]2
Reactant: CSC
Reactant: Nc1ccc(OC23CC4CC(CC(C4)C2)C3)cc1
Agent: ClCl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CSCc1cc(OC23CC4CC(CC(C4)C2)C3)ccc1N
Temperature: 25 °C

Procedure:
To 6.2 g. (0.088 mole) of chlorine in 240 ml. of CH2Cl2 in a one-liter 3-neck flask cooled to -70° to -73° was added dropwise with stirring a cold (~-70°) solution of 5.7 g. (0.092 mole) of dimethyl sulfide in 20 ml. of CH2Cl2. The solution was stirred for several minutes, and then a solution of 21.4 g. (0.088 mole) of 4-(1-adamantyloxy)-aniline and 8.9 g. (0.088 mole) of triethylamine in 400 ml. of CH2Cl2 cooled either to -70° or to -40° to -50° was added dropwise rapidly. Then the mixture was either stirred at -70° and gradually allowed to warm to room temperature during four hours and then cooled again to -65° or it was stirred at -70° for two hours followed in either case by the addition of 51.8 g. of 25% sodium methoxide in methanol solution, removal of the cold bath, and stirring at room temperature for 12 to 18 hours.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:12]2[CH:17]=[CH:16][C:15]([C:18]#[N:19])=[C:14]([OH:20])[CH:13]=2)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH:21]1([C:24]([CH2:26]Br)=[O:25])[CH2:23][CH2:22]1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[Cl:1][C:2]1[C:3]([C:12]2[CH:17]=[CH:16][C:15]([C:18]#[N:19])=[C:14]([O:20][CH2:26][C:24]([CH:21]3[CH2:23][CH2:22]3)=[O:25])[CH:13]=2)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:9])[F:10])[CH:7]=1
Reactant: N#Cc1ccc(-c2ncc(C(F)(F)F)cc2Cl)cc1O
Reactant: O=C(CBr)C1CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: N#Cc1ccc(-c2ncc(C(F)(F)F)cc2Cl)cc1OCC(=O)C1CC1
Temperature: 23 °C
Reaction time: 40 h

Procedure:
A mixture of 1.5 g of 3-chloro-2-(4-cyano-3-hydroxyphenyl)-5-trifluoromethylpyridine, 1.2 g of bromomethyl cyclopropyl ketone, 1.5 g of potassium carbonate and 50 ml of anhydrous dimethylformamide was stirred for 40 hours at 23° C. After addition of 200 ml of water, the mixture was extracted three times with 50 ml of methyl tert-butyl ether each time. The combined organic phases were washed with 50 ml of water, then dried over sodium sulfate and concentrated. The residue which remained was crystallized by triturating with n-hexane. Yield: 1.6 g of white crystals having a melting point of 115°-116° C.
Reaction SMILES: [Br:1]Br.[CH3:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[C:8]([Cl:13])[CH:7]=1)=[O:5].[Al+3].[Cl-].[Cl-].[Cl-].O>C(OCC)C>[Cl:13][C:8]1[CH:7]=[C:6]([CH:11]=[CH:10][C:9]=1[Cl:12])[C:4](=[O:5])[CH2:3][Br:1]
Reactant: BrBr
Reactant: CC(=O)c1ccc(Cl)c(Cl)c1
Agent: [Al+3]
Agent: [Cl-]
Solvent: CCOCC
Solvent: O
Product: O=C(CBr)c1ccc(Cl)c(Cl)c1

Procedure:
Bromine in a quantity of 10.2 ml (0.2 mol) is added dropwise to a mixture of 37.8 g 3.4-dichloroacetophenone and approx. 1.0 g anhydrous AlCl3 in 600 ml dry diethylether while stirring and cooling in ice. After stirring for 0.5 hr at 0° C. and 1.5 hr at room temperature, 30 ml water are added slowly. The organic phase is separated, washed twice with water, dried and evaporated to dryness. A small amount of petroleum ether (40-60) is added to the residue and the mixture is stirred at approx. 0° C. The desired 3.4-dichlorophenacylbromide is obtained as a crystalline material in a yield of 39.8 g (74%); melting point 55°-58° C.; TLC (CH2Cl2)=0.5.
Reaction SMILES: [ClH:1].[N:2]1([CH2:8][CH2:9][O:10][C:11]2[CH:19]=[CH:18][C:14]([C:15](O)=[O:16])=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.S(Cl)([Cl:22])=O>CN(C)C=O.ClCCCl>[ClH:22].[N:2]1([CH2:8][CH2:9][O:10][C:11]2[CH:19]=[CH:18][C:14]([C:15]([Cl:1])=[O:16])=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1ccc(OCCN2CCCCC2)cc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: ClCCCl
Product: O=C(Cl)c1ccc(OCCN2CCCCC2)cc1

Procedure:
An acylating agent, in acid chloride form, was prepared by combining 26.3 g. of 4-(2-piperidinoethoxy)benzoic acid, hydrochloride, 36.5 g. of thionyl chloride and 1 drop of dimethylformamide in 200 ml. of 1,2-dichloroethane, and stirring the mixture under reflux for 2 hours under a nitrogen atmosphere. The mixture was then evaporated to dryness under vacuum to obtain the desired 4-(2-piperidinoethoxy)benzoyl chloride, hydrochloride, which was dissolved in 1 liter of 1,2-dichloroethane. To the solution was added 20 g. of 6-acetoxy-2-(4-acetoxyphenyl)benzo[b]thiophene and the mixture was stirred vigorously. To it was then added, over about 3 minutes, 73.4 g. of aluminum chloride. During the addition, the reaction mixture turned dark brown and hydrogen chloride evolved. The mixture was then stirred for one hour, and was poured over 1 liter of ice-water. The layers were separated, and the aqueous layer was extracted three times with 200 ml. portions of warm chloroform. The organic layers were combined and dried over magnesium sulfate, and were then filtered and evaporated under vacuum to obtain a brownish-yellow oil, which are not purified. The presence of the desired product was confirmed by thin layer chromatography (TLC) on silica gel, eluting with 9/1 chloroform/methanol, which showed that the major constituent ran at the same Rf as authentic 6-acetoxy-2l -(4-acetoxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]-benzo[b]thiophene.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([OH:23])=[C:14]([C:20](O)=[O:21])[N:15]=[C:16]2[Cl:19])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:25][O:26][C:27](=[O:31])[C@H:28]([CH3:30])[NH2:29]>>[CH3:25][O:26][C:27](=[O:31])[C@@H:28]([NH:29][C:20]([C:14]1[N:15]=[C:16]([Cl:19])[C:17]2[C:12]([C:13]=1[OH:23])=[CH:11][CH:10]=[C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH:18]=2)=[O:21])[CH3:30]
Reactant: COC(=O)[C@H](C)N
Reactant: O=C(O)c1nc(Cl)c2cc(OCc3ccccc3)ccc2c1O
Agent: Cl
Product: COC(=O)[C@H](C)NC(=O)c1nc(Cl)c2cc(OCc3ccccc3)ccc2c1O

Procedure:
7-Benzyloxy-1-chloro-4-hydroxy-isoquinoline-3-carboxylic acid, 0.33 g, was coupled with L-Alanine methyl ester hydrochloride, 0.150 g, analogously to Example A-1 a). 0.264 G of white solid were obtained: MS-(+)-ion, M+1=415 amu.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[OH:10])=[CH:2][CH3:3].C1(OCC=C)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].Br[CH:28]([CH3:33])[C:29]([O:31][CH3:32])=[O:30]>O.CN(C)C=O>[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][CH:28]([CH3:33])[C:29]([O:31][CH3:32])=[O:30])=[CH:2][CH3:3]
Reactant: COC(=O)C(C)Br
Reactant: CC=Cc1ccccc1O
Agent: C=CCOc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC=Cc1ccccc1OC(C)C(=O)OC
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 500 mg (3.72 mmol) of 2-propenylphenol (E/Z mixture), prepared by Claisen rearrangement of phenylallylether followed by double bond isomerisation, 1.02 g of potassium carbonate (0.74 mmol) and 745 mg of rac. methyl 2-bromopropionate (4.46 mmol) and 10 ml of dimethylformamide was stirred overnight at RT and then for 4 hours at 80° C. The reaction mixture was then added to 40 ml of water and extracted three times with 30 ml diethyl ether. The organic phase was washed with 5% sodium hydroxide solution, separated off, dried with Na2SO4 and concentrated by evaporation. 685 mg (83.6% of theory) of virtually pure methyl 2-(2-propenyl-phenyloxy)propionate were obtained.
Reaction SMILES: [CH:1]1([NH2:4])[CH2:3][CH2:2]1.[CH3:5][O:6][C:7]1[N:12]=[C:11]2[C:13]([C:17]3[N:27]([S:28]([C:31]4[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=4)(=[O:30])=[O:29])[C:20]4[N:21]=[CH:22][CH:23]=[C:24]([CH:25]=O)[C:19]=4[CH:18]=3)=[CH:14][N:15]([CH3:16])[C:10]2=[CH:9][C:8]=1[O:38][CH3:39].S([O-])([O-])(=O)=O.[Na+].[Na+].[BH4-].[Na+]>ClCCl.CO>[CH:1]1([NH:4][CH2:25][C:24]2[CH:23]=[CH:22][N:21]=[C:20]3[N:27]([S:28]([C:31]4[CH:32]=[CH:33][C:34]([CH3:37])=[CH:35][CH:36]=4)(=[O:30])=[O:29])[C:17]([C:13]4[C:11]5=[N:12][C:7]([O:6][CH3:5])=[C:8]([O:38][CH3:39])[CH:9]=[C:10]5[N:15]([CH3:16])[CH:14]=4)=[CH:18][C:19]=23)[CH2:3][CH2:2]1
Reactant: NC1CC1
Reactant: COc1cc2c(nc1OC)c(-c1cc3c(C=O)ccnc3n1S(=O)(=O)c1ccc(C)cc1)cn2C
Agent: O=S(=O)([O-])[O-]
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: COc1cc2c(nc1OC)c(-c1cc3c(CNC4CC4)ccnc3n1S(=O)(=O)c1ccc(C)cc1)cn2C
Reaction time: 48 h

Procedure:
To a solution of 0.141 cm3 of cyclopropylamine in 6 cm3 of dichloromethane, under an inert atmosphere of argon at a temperature in the region of 20° C., are added 0.2 g of 2-(5,6-dimethoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-carbaldehyde and 0.4 g of sodium sulfate. Stirring is continued for 48 hours at room temperature. 6 cm3 of methanol and 0.031 g of sodium borohydride are added. The reaction medium is stirred at the same temperature for 24 hours. 100 cm3 of dichloromethane are added. The precipitate formed is filtered off and the filtrate is concentrated under reduced pressure and then purified by flash column chromatography (SiO2, dichloromethane/ethyl acetate 80/20 by volume as eluents) to give 0.110 g of cyclopropyl-[2-(5,6-dimethoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-ylmethyl]-amine with the following characteristics:
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:10][C:11]([CH2:15][NH:16][C:17]([CH:19]3[CH2:24][CH2:23][CH2:22][NH:21][CH2:20]3)=[O:18])=[C:12]([CH3:14])[N:13]=2)=[CH:5][CH:4]=1.[CH3:25][O:26][C:27]([C:29]1[CH:30]=[C:31](OB(O)O)[CH:32]=[CH:33][CH:34]=1)=[O:28].C(N(CC)CC)C>C(OCC)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:10][C:11]([CH2:15][NH:16][C:17]([CH:19]3[CH2:24][CH2:23][CH2:22][N:21]([C:33]4[CH:34]=[C:29]([CH:30]=[CH:31][CH:32]=4)[C:27]([O:26][CH3:25])=[O:28])[CH2:20]3)=[O:18])=[C:12]([CH3:14])[N:13]=2)=[CH:5][CH:4]=1
Reactant: Cc1nc(-c2ccc(Cl)cc2)sc1CNC(=O)C1CCCNC1
Reactant: COC(=O)c1cccc(OB(O)O)c1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: Cl
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: COC(=O)c1cccc(N2CCCC(C(=O)NCc3sc(-c4ccc(Cl)cc4)nc3C)C2)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 13.1 %

Procedure:
N-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]methyl]piperidine-3-carboxamide hydrochloride (123 mg, 0.318 mmol) was suspended in diethyl ether. The suspension washed sequentially with a 0.1 mol/L aqueous sodium hydroxide solution and brine and was dried over magnesium sulfate. The solvent was then evaporated and the resulting residue was dissolved in dichloromethane (10 mL). To this solution, 3-(methoxycarbonyl)phenylboric acid (114 mg, 0.636 mmol), molecular sieves 4 Å (300 mg), copper (II) acetate (122 mg, 0.636 mmol) and triethylamine (0.222 mL, 1.59 mmol) were added and the mixture was stirred at room temperature for 16 hours. Subsequently, the reaction mixture was filtered through Celite and a saturated aqueous sodium bicarbonate solution was added to the filtrate. The mixture was extracted with ethyl acetate. The extract washed with brine, followed by drying over magnesium sulfate and evaporation of the solvent. Purification of the resulting residue by silica gel column chromatography (hexane:ethyl acetate=2:1->0:1) gave 20.1 mg (13%) of the desired compound as a colorless powder.
Reaction SMILES: [NH:1]=[C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[SH:4](=[O:17])([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[NH:3]1.[C:18]([O:21][C:22]1[C:23](=[CH:27][CH:28]=[CH:29][CH:30]=1)[C:24](O)=[O:25])(=[O:20])[CH3:19].C(N(CC)CC)C>C(Cl)(Cl)Cl>[C:18]([O:21][C:22]1[C:23](=[CH:27][CH:28]=[CH:29][CH:30]=1)[C:24]([N:1]=[C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[SH:4](=[O:17])([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[NH:3]1)=[O:25])(=[O:20])[CH3:19]
Reactant: CC(=O)Oc1ccccc1C(=O)O
Reactant: N=C1N[SH](=O)(c2ccccc2)c2ccccc21
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: CC(=O)Oc1ccccc1C(=O)N=C1N[SH](=O)(c2ccccc2)c2ccccc21

Procedure:
2.4 g. 3-imino-1-phenyl-3H-1,2-benzisothiazole-1-oxide are boiled for 1 hour with 2 g. acetyl-salicylic acid and 1.32 g. triethylamine in 100 cc. chloroform. After working up in the usual manner, there is obtained 3-(acetylsalicyloylimino)-1-phenyl-3H-1,2-benzisothiazole-1-oxide in the form of colourless crystals which, after recrystallisation from ethyl acetate, melts at 160°C. Structurally, the compounds of this invention are: ##SPC4##Example R1R2 salt melting point (°C)______________________________________ 4 methyl phenoxy -- 138-139 5 phenyl methyl -- 119 6 phenyl ethyl -- 170 7 phenyl iso- -- 122 propyl 8 methyl -- 168-169 9 phenyl -- 13410 methyl -- 17011 methyl methoxy -- 16612 phenyl ethoxy -- 16313 methyl butoxy-2 -- 12514 phenyl phenoxy -- 17315 methyl --O--CH2 --CH2 -- -- 108-190 OCH316 phenyl --CH2 --O--C6H4 -- -- 196 Cl(r)17 phenyl --CH2 --C6H5 -- 12018 methyl --O--C6H11 -- 126-12819 phenyl --C6H4 --O--CO-- -- 160 CH 3 (o)______________________________________
Reaction SMILES: [OH:1][CH2:2][CH2:3][NH:4][C:5](=[O:8])[O:6][CH3:7].[Br:9][CH:10]([CH3:14])[C:11](Br)=[O:12]>>[Br:9][CH:10]([CH3:14])[C:11]([O:1][CH2:2][CH2:3][NH:4][C:5](=[O:8])[O:6][CH3:7])=[O:12]
Reactant: CC(Br)C(=O)Br
Reactant: COC(=O)NCCO
Product: COC(=O)NCCOC(=O)C(C)Br

Procedure:
by using methyl 2-hydroxyethylcarbamate and 2-bromopropionyl bromide there is obtained methyl 2-(2-bromopropionyloxy)-ethylcarbamate, nD20 1.4779;
Reaction SMILES: C([O:4][C:5]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:6]=1[O:7][CH2:8][C@H:9]1[CH2:11][O:10]1)C=C.C(=O)(O)[O-].[Na+].[C:22]1(C)[CH:27]=C(C)C=C(C)[CH:23]=1>>[CH2:27]([C:15]1[C:5]2[O:4][C@@H:9]([CH2:11][OH:10])[CH2:8][O:7][C:6]=2[CH:12]=[C:13]([Cl:16])[CH:14]=1)[CH:22]=[CH2:23]
Reactant: C=CCOc1ccc(Cl)cc1OC[C@H]1CO1
Reactant: Cc1cc(C)cc(C)c1
Agent: O=C([O-])O
Agent: [Na+]
Product: C=CCc1cc(Cl)cc2c1O[C@@H](CO)CO2
Temperature: 25 °C
Reaction time: 24 h

Procedure:
(R)-2-(2-Allyloxy-5-chlorophenoxymethyl)-oxirane (9.2 g, 38 mmole) was dissolved in 500 ml of mesitylene and refluxed under nitrogen for 48 hours. The solvent was then removed in vacuum and replaced with 500 ml of ethanol. Sodium bicarbonate (50 g, 0.60 mole) was added and the mixture stirred at room temperature under nitrogen for 24 hours. The mixture was then filtered and concentrated in vacuum. The solvent was replaced with 500 ml of methylene chloride and the solution was washed with water and with saturated brine, dried over sodium sulfate, filtered and evaporated in vacuum. The residue was column chromatographed on silica gel using chloroform as eluant to give 8.9 g of the title compound as a colorless oil. 1H (CDCl3) singlet, 6.80 δ (1 H); singlet, 6.73 δ (1 H); multiplet, 5.95 δ (1 H); doublet, 5.10 δ (1 H); doublet, 5.05 δ (1 H); multiplet, 4.25 δ (2 H); multiplet, 4.10 δ (1 H); multiplet, 3.85 δ (2 H); multiplet, 3.30 δ (2 H); broad singlet, 2.00 δ (1 H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[CH:4](Cl)[CH2:5][S:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[N-:16]=[N+:17]=[N-:18].[Na+]>CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)C.[Cl-].O>[CH3:1][O:2][C:3](=[O:15])[CH:4]([N:16]=[N+:17]=[N-:18])[CH2:5][S:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: [N-]=[N+]=[N-]
Reactant: COC(=O)C(Cl)CSCc1ccccc1
Agent: CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Product: COC(=O)C(CSCc1ccccc1)N=[N+]=[N-]
Yield: 98.7 %

Procedure:
15.0 grams (61.3 mmoles) of the 2-chloro-3-benzylmercapto-propionic acid methyl ester produced in Example 3 were stirred with 5.98 grams (92.0 mmoles) of sodium azide and 1.5 grams of Aliquat 336 in 30 ml of water for 7 hours at 45° C. After working up according to Example 2 there were obtained 15.2 grams (99% of theory) of 2-azido-3-benzylmercapto-propionic acid methyl ester.