Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2][CH2:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]2[O:13][CH2:14][O:15][C:9]=2[CH:8]=1)=[O:5].[C:16]1([N:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(N(CC)CC)C>CN(C)C=O>[C:16]1([N:22]2[CH2:27][CH2:26][N:25]([CH2:2][CH2:3][C:4]([NH:6][C:7]3[CH:12]=[CH:11][C:10]4[O:13][CH2:14][O:15][C:9]=4[CH:8]=3)=[O:5])[CH2:24][CH2:23]2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: c1ccc(N2CCNCC2)cc1
Reactant: O=C(CCCl)Nc1ccc2c(c1)OCO2
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: O=C(CCN1CCN(c2ccccc2)CC1)Nc1ccc2c(c1)OCO2
Temperature: 80 °C
Reaction time: 20 h
Yield: 109.5 %

Procedure:
To N-(3-chloropropionyl)-3,4-methylenedioxyaniline (2.0 g) dissolved in N,N-dimethylformamide (20 ml) were added N-phenylpiperazine (1.6 g) and triethylamine (3 ml) and the mixture was stirred at 80° C. for 20 hours in a nitrogen atmosphere. The reaction mixture was evaporated in vacuo and to the residue were added ethyl acetate and 2N sodium hydroxide solution. After the aqueous layer was removed, the ethyl acetate layer was washed twice with water and dried over anhydrous sodium sulfate. The ethyl acetate was then distilled off and the residual solid was recrystallized from ethanol to give N-[3-(4-phenyl-1-piperazinyl)propionyl]-3,4-methylenedioxyaniline (3.4 g, 90% yield).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH2:12][CH2:13][OH:14])[C:10]=1[OH:11])[C@H:7]([CH2:15][CH2:16][NH:17][C:18](=[O:21])[CH2:19][CH3:20])[CH2:6][CH2:5]2.C(N(CC)CC)C>[C].[Pd].CO>[OH:11][C:10]1[C:9]([CH2:12][CH2:13][OH:14])=[C:8]2[C:4]([CH2:5][CH2:6][C@H:7]2[CH2:15][CH2:16][NH:17][C:18](=[O:21])[CH2:19][CH3:20])=[CH:3][CH:2]=1
Reactant: CCC(=O)NCC[C@@H]1CCc2cc(Br)c(O)c(CCO)c21
Agent: [Pd]
Solvent: CCN(CC)CC
Solvent: CO
Product: CCC(=O)NCC[C@@H]1CCc2ccc(O)c(CCO)c21
Yield: 91.2 %

Procedure:
A methanol suspension of (S)-N-[2-(5-bromo-6-hydroxy-7-(2-hydroxyethyl)indan-1-yl)ethyl]propionamide (590 mg, 1.66 mmol.), triethylamine (184 mg, 1.82 mmol.) and 5% palladium-carbon (100 mg) was subjected to catalytic reduction under hydrogen atmosphere. At the time when the calculated volume of hydrogen was absorbed, the catalyst was filtered off. The filtrate was made weakly acidic with dilute hydrochloric acid, followed by extracting the organic matter with a mixture of ethyl acetate:butanol=1.1. The extract solution was dried over anhydrous magnesium sulfate, then the solvent was distilled off under reduced pressure, followed by washing with diethyl ether to afford the title compound (yield 0.42 g, 91%).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([F:11])=[C:8]([CH:10]=1)[NH2:9])([O-:3])=[O:2].CO[CH:14]1[CH2:18][CH2:17][CH:16](OC)O1>C(O)(=O)C>[F:11][C:7]1[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:10][C:8]=1[N:9]1[CH:14]=[CH:18][CH:17]=[CH:16]1
Reactant: COC1CCC(OC)O1
Reactant: Nc1cc([N+](=O)[O-])ccc1F
Solvent: CC(=O)O
Product: O=[N+]([O-])c1ccc(F)c(-n2cccc2)c1
Temperature: 110 °C
Yield: 78 %

Procedure:
5-Nitro-2-fluoroaniline (7.0 g, 44.8 mmol) was taken up in acetic acid (60 mL) in a 250 mL round bottomed flask and treated with 2,5-dimethoxytetrahydrofuran (6.3 mL, 49.8 mmol). The resulting mixture was heated to 110° C. for 4 hours. TLC analysis indicated complete conversion of starting material to product after 4 hours. Thus, the reaction mixture was cooled to ambient temperature, transferred to a separatory funnel and partitioned (CH2Cl2//H2O). The organic phase was washed with H2O (3×50 mL), brine (3×50 mL), dried over Na2SO4 and evaporated in vacuo to give a light brown residue. The residue was purified by flash chromatography (hexanes→1:9 EtOAc/hexanes) to afford the title compound as a light yellow solid (7.2 g, 78%).
Reaction SMILES: ClC(Cl)(Cl)CO[C:5](=[O:14])[NH:6][C:7]1[O:11][N:10]=[C:9]([CH3:12])[C:8]=1[CH3:13].[C:17]1([C:23]2[CH:24]=[CH:25][C:26]([N:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)=[N:27][CH:28]=2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(N(C(C)C)CC)(C)C.CS(C)=O>O>[CH3:12][C:9]1[C:8]([CH3:13])=[C:7]([NH:6][C:5]([N:32]2[CH2:33][CH2:34][N:29]([C:26]3[CH:25]=[CH:24][C:23]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:28][N:27]=3)[CH2:30][CH2:31]2)=[O:14])[O:11][N:10]=1
Reactant: c1ccc(-c2ccc(N3CCNCC3)nc2)cc1
Reactant: Cc1noc(NC(=O)OCC(Cl)(Cl)Cl)c1C
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: CS(C)=O
Product: Cc1noc(NC(=O)N2CCN(c3ccc(-c4ccccc4)cn3)CC2)c1C
Yield: 45.6 %

Procedure:
A solution of 2,2,2-trichloroethyl(3,4-dimethylisoxazol-5-yl)carbamate (251 mg, 0.872 mmol), 1-(5-phenylpyridin-2-yl)piperazine (200 mg, 0.872 mmol), diisopropylethylamine (0.304 ml, 1.74 mmol) and dimethylsulfoxide (4 ml) was stirred at 70° C. for 12 hours, then the reaction solution was poured into water, and extracted with ethyl acetate. The extract was washed with water, and dried over anhydrous magnesium sulfate. The solvent was distilled away under reduce pressure, and the residue was recrystallized from ethyl acetate to give the titled compound 150 mg (45.6%) as solid product.
Reaction SMILES: [OH:1][CH:2]1[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:3]1.[CH2:22](Br)[CH:23]=[CH2:24].C(=O)([O-])[O-].[K+].[K+]>>[CH2:24]([O:14][C:11]1[CH:10]=[CH:9][C:8]([CH:7]2[CH2:6][CH2:5][N:4]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:3][CH:2]2[OH:1])=[CH:13][CH:12]=1)[CH:23]=[CH2:22]
Reactant: C=CCBr
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(O)cc2)C(O)C1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: C=CCOc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2O)cc1

Procedure:
In an analogous manner to the procedure described in Example 14, by alkylating tert-butyl (3RS,4RS)-3-hydroxy-4-(4-hydroxy-phenyl)-piperidine-1-carboxylate with allyl bromide in the presence of potassium carbonate there was obtained tert-butyl (3RS,4RS)-4-(4-allyloxy-phenyl)-3-hydroxy-piperidine-1-carboxylate as a colourless solid; m.p.: 113° C. (hexane).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[S:9](Cl)(=[O:11])=[O:10].N1C=CC=CC=1.[NH2:19][C:20]1[CH:21]=[CH:22][C:23]2[O:27][N:26]=[CH:25][C:24]=2[CH:28]=1.C([O-])(O)=O.[Na+]>ClCCl>[O:27]1[C:23]2[CH:22]=[CH:21][C:20]([NH:19][S:9]([C:3]3[CH:4]=[C:5]([Cl:8])[CH:6]=[CH:7][C:2]=3[Cl:1])(=[O:11])=[O:10])=[CH:28][C:24]=2[CH:25]=[N:26]1
Reactant: Nc1ccc2oncc2c1
Reactant: O=S(=O)(Cl)c1cc(Cl)ccc1Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=S(=O)(Nc1ccc2oncc2c1)c1cc(Cl)ccc1Cl
Reaction time: 0.08 h
Yield: 68 %

Procedure:
To a solution of 2,5-dichlorobenzenesulphonyl chloride (192 mg, 0.783 mmol), in dichloromethane (4 mL) was added pyridine (150 μL, 1.86 mmol) and the mixture was stirred under N2 for 5 min, after which time 5-amino-1,2-benzisoxazole (100 mg, 0.746 mmol) was added. The resulting mixture was stirred for 2 h at room temperature, then saturated NaHCO3 solution (10 mL) was added and the mixture was extracted into ethyl acetate (20 mL). The organic phase was washed with brine, dried (Na2SO4), filtered and evaporated to give a residue that was purified using flash chromatography to afford a white solid (174 mg, 68%), single spot at Rf 0.68 (1:1 hexane:ethyl acetate). mp 172.9-173.6° C., HPLC purity 99+% (tR 2.41 min in 10% water-acetonitrile). 1H NMR (CDCl3): δ 8.64 (1H, s), 7.89 (1H, d, J=2.2 Hz), 7.56-7.28 (5H, m). LCMS: 341.07 (M−). FAB-MS (MH+, C13H8Cl2N2O3S): calcd 342.9711, found 342.9710.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9](Cl)[CH2:10][C:11](CC(Cl)C1C=CC(Cl)=CC=1Cl)=O.[NH2:25][C:26]([NH2:28])=[S:27]>C(O)C>[ClH:1].[NH2:25][CH:26]1[N:28]=[C:9]([C:3]2[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=2[Cl:1])[CH:10]=[CH:11][S:27]1
Reactant: O=C(CC(Cl)c1ccc(Cl)cc1Cl)CC(Cl)c1ccc(Cl)cc1Cl
Reactant: NC(N)=S
Solvent: CCO
Product: Cl
Product: NC1N=C(c2ccc(Cl)cc2Cl)C=CS1
Reaction time: 3.5 h

Procedure:
24.0 g (0.1 mol) of 2.4-dichloro-phenyl-β-chloro-ethylketone (95%) are heated under reflux with 7.6 g (0.1 mol) of thiourea in 100 ml of ethanol. After approximately 3.5 hours, the reaction product has separated off as colourless crystals; 23.7 g (approximately 85% of the theory) of 2-amino-4-(2,4-dichloro-phenyl)-1,3-thiazine-hydrochloride are obtained as colourless crystals with a melting point of 236° C.
Reaction SMILES: [OH:1][CH:2]([C:8]1[CH:9]=[N:10][CH:11]=[C:12]([C:14]2[CH:15]=[C:16]3[C:22]([C:23]4[O:24][CH:25]=[CH:26][N:27]=4)=[CH:21][N:20](COCC[Si](C)(C)C)[C:17]3=[N:18][CH:19]=2)[CH:13]=1)[C:3]([N:5]([CH3:7])[CH3:6])=[O:4]>ClCCl.FC(F)(F)C([O-])=O>[OH:1][CH:2]([C:8]1[CH:9]=[N:10][CH:11]=[C:12]([C:14]2[CH:15]=[C:16]3[C:22]([C:23]4[O:24][CH:25]=[CH:26][N:27]=4)=[CH:21][NH:20][C:17]3=[N:18][CH:19]=2)[CH:13]=1)[C:3]([N:5]([CH3:6])[CH3:7])=[O:4]
Reactant: CN(C)C(=O)C(O)c1cncc(-c2cnc3c(c2)c(-c2ncco2)cn3COCC[Si](C)(C)C)c1
Agent: O=C([O-])C(F)(F)F
Solvent: ClCCl
Product: CN(C)C(=O)C(O)c1cncc(-c2cnc3[nH]cc(-c4ncco4)c3c2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 27.5 %

Procedure:
2-Hydroxy-N,N-dimethyl-2-{5-[3-oxazol-2-yl-1(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyridin-3-yl}-acetamide (10 mg, 0.02 mmol) was stirred in dichloromethane/trifluoroacetate acid (1 ml/1 ml) at room temperature for 2 hours. The solvents were removed under vacuum and the crude was stirred in dichloromethane/ethylenediamine (1 ml/1 ml) for 2 hours at room temperature. Again the solvents was removed under vacuum and the crude was dissolved in DMSO, filtered and purified by reverse phase HPLC, lyophilized afforded 2-hydroxy-N,N-dimethyl-2-{5-[3-oxazol-2-yl-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyridin-3-yl}-acetamide (2 mg, 31% yield). 1H NMR (500 MHz, DMSO-d6) δ 2.81 (s, 3H), 2.96 (s, 3H), 5.58 (s, 1H), 6.22 (s, 1H), 7.28 (s, 1H), 8.04 (t, 1H), 8.76 (s, 1H), 8.22 (s, 1H), 8.52 (d, 1H), 8.62 (s, 2H0, 8.83 (d, 1H). MS: m/z 364.0 (M+H+).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7]([CH:9]([CH2:12][CH2:13][CH2:14][CH3:15])[CH2:10][NH2:11])[CH3:8].[CH:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][C:17]=1[O:26][CH2:27][CH2:28][CH2:29]Cl>CS(C)=O.O>[CH2:7]([CH:9]([CH2:12][CH2:13][CH2:14][CH3:15])[CH2:10][NH:11][CH2:29][CH2:28][CH2:27][O:26][C:17]1[CH:18]=[CH:19][C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:16]=1)[CH3:8]
Reactant: ClCCCOc1ccc2ccccc2c1
Reactant: CCCCC(CC)CN
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: CCCCC(CC)CNCCCOc1ccc2ccccc2c1
Temperature: 140 °C

Procedure:
A mixture of anhydrous potassium carbonate (10 gm, in excess) and 2-ethyl-n-hexylamine (0.35 ml, 0.003 mole) was taken in dry DMSO (40 ml). Now 3-(2-naphthyloxy)-1-chloropropane (0.5 gm, 0.002 mole) was added in it. Reaction mixture was refluxed at 140° C. for 7 hrs and the reaction was completed as checked by TLC. Reaction mixture was poured in distilled water (60 ml) and extracted with ethyl acetate thrice. The organic layer was separated and concentrated to get oily compound which was later crystallized by benzene hexane to get N-(2-ethyl-n-hexyl)-(3-(naphthalen-2-yloxy) propyl)amine solid, m.p. 97° C., (yield 0.6 gm, 84.8%).
Reaction SMILES: [OH-].[NH4+:2].C[O:4][C:5]([C:7]1[CH:12]=[C:11]([Br:13])[C:10]([OH:14])=[C:9]([Br:15])[N:8]=1)=O>>[Br:13][C:11]1[C:10]([OH:14])=[C:9]([Br:15])[N:8]=[C:7]([C:5]([NH2:2])=[O:4])[CH:12]=1
Reactant: [NH4+]
Reactant: COC(=O)c1cc(Br)c(O)c(Br)n1
Agent: [OH-]
Product: NC(=O)c1cc(Br)c(O)c(Br)n1
Reaction time: 48 h
Yield: 80 %

Procedure:
Concentrated ammonium hydroxide, 180 ml, was added to 10 g of 4,6-dibromo-5-hydroxy-2-pyridinecarboxylic acid methyl ester and heated at 45°-60° C. for 1 hour. After the mixture was kept for 2 days at room temperature, the solid was filtered and successively washed with dilute HCl (to neutralize the ammonia) and then with methanol and benzene to remove any unreacted starting material. The product was isolated in 80% yield; m.p. 261-266° C. (best sample: m.p. 275° C.).
Reaction SMILES: [CH3:1][Si:2]([CH3:13])([CH2:4][Si:5](Cl)([Cl:11])[CH2:6][Si:7]([CH3:10])([CH3:9])[CH3:8])[CH3:3].[CH3:14][OH:15]>>[CH3:1][Si:2]([CH3:13])([CH2:4][Si:5]([Cl:11])([O:15][CH3:14])[CH2:6][Si:7]([CH3:10])([CH3:9])[CH3:8])[CH3:3]
Reactant: C[Si](C)(C)C[Si](Cl)(Cl)C[Si](C)(C)C
Reactant: CO
Product: CO[Si](Cl)(C[Si](C)(C)C)C[Si](C)(C)C
Temperature: 70 °C
Yield: 74 %

Procedure:
13.7 g(50 mmoles) of 2,2,6,6-tetramethyl-4,4-dichloro-2,4,6-trisilaheptane were placed in the flask of the same set as Example 1, and then 1.8 g(60 mmoles) of dry methanol were added. The mixture was heated at 70° C. for 2 hrs. The amount of the product was 9.92 g and the yield 74%.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH2:11]([N:18]1[CH2:23][CH:22]2[CH:20]([CH:21]2[CH2:24][OH:25])[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>C(Cl)Cl>[CH2:11]([N:18]1[CH2:23][CH:22]2[CH:20]([CH:21]2[CH:24]=[O:25])[CH2:19]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: OCC1C2CN(Cc3ccccc3)CC12
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: O=CC1C2CN(Cc3ccccc3)CC12
Temperature: -65 °C
Yield: 75.2 %

Procedure:
Oxalyl chloride (0.88 ml, 17.73 mmol) was added to a stirred flask of DCM (100 ml) under N2 and the solution cooled to an internal temperature of −65° C. DMSO (1.26 ml, 17.73 mmol) was then added dropwise, keeping the internal temperature at −65° C. or below at all times. A solution of (3-benzyl-3-azabicyclo[3.1.0]hex-6-yl)methanol (2.00 g, 9.85 mmol) in DCM (50 ml) was then added to the reaction mixture slowly, again making sure the internal temperature did not rise above −65° C. After this addition was complete, triethylamine (5.90 ml, 42.35 mmol) was slowly added to the reaction, again making sure the internal temperature did not rise above −65° C. After addition was complete the reaction was allowed to warm up to r.t. and solvent removed in vacuo. The residue was purified by column chromatography (25% EtOAc in heptane) to give the title compound as a light yellow oil (1.49 g, 76%). LCMS purity 90%, m/z 202 [M+H]+, 1H NMR (300 MHz, d6-DMSO) δ: 2.11 (2H, m), 2.44 (1H, m), 2.50 (2H, d, J=9.3 Hz), 3.07 (2H, d, J=9.3 Hz), 3.64 (2H, s), 7.21-7.35 (5H, m), 9.31 (1H, d, J=4.8 Hz).
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:10]=[C:9]([CH3:11])[C:8]([C:12](=[O:14])[CH3:13])=[C:7]([CH3:15])[CH:6]=1)([CH3:3])[CH3:2].[Br-:16].[Br-].[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC>C(#N)C>[Br:16][CH2:13][C:12]([C:8]1[C:9]([CH3:11])=[CH:10][C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[CH:6][C:7]=1[CH3:15])=[O:14]
Reactant: [Br-]
Reactant: CC(=O)c1c(C)cc(OC(C)C)cc1C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CC#N
Product: Cc1cc(OC(C)C)cc(C)c1C(=O)CBr
Temperature: 25 °C
Reaction time: 8 h
Yield: 99 %

Procedure:
To a solution of 1-(4-isopropoxy-2,6-dimethylphenyl)ethanone (4.3 g, 20.9 mmol) in acetonitrile (41.7 mL) was added tetrabutylammoniumtribromide (TBABr3, 11.1 g, 22.9 mmol). The reaction was stirred at room temperature overnight. The solution was concentrated under reduced pressure, added with water, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous MgSO4(s), and concentrated under reduced pressure to give 2-bromo-1-(4-isopropoxy-2,6-dimethylphenyl)ethanone (5.9 g), which was used directly for the next step without further purification.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[N:10][C:9]2[S:8](=[O:13])(=[O:12])[N:7]=[CH:6][NH:5][C:4]=2[CH:3]=1.[C:14](=O)([O-])[O-].[K+].[K+].C1(C)C=CC(S(OC)(=O)=O)=CC=1>C(#N)C.O>[CH3:14][N:5]1[C:4]2[CH:3]=[C:2]([CH3:1])[CH:11]=[N:10][C:9]=2[S:8](=[O:13])(=[O:12])[N:7]=[CH:6]1
Reactant: O=C([O-])[O-]
Reactant: Cc1cnc2c(c1)NC=NS2(=O)=O
Agent: COS(=O)(=O)c1ccc(C)cc1
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: Cc1cnc2c(c1)N(C)C=NS2(=O)=O

Procedure:
A solution of 0.6 g of 6-methyl-4H-pyrido[3,2-e][1,2,4]thiadiazine 1,1-dioxide (Example 75) in 15 cm3 of acetonitrile is treated with 2.5 g of potassium carbonate and 0.9 g of methyl p-toluenesulfonate. After refluxing for 16 hours, the solvent is removed under partial vacuum and the solid obtained is taken up in 15 cm3 of water. The precipitate is collected on a filter, washed with water and dried.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]2[CH:16]=[CH:17][C:18]3[NH:23][C:22](=[O:24])[O:21][C:20]([CH3:26])([CH3:25])[C:19]=3[CH:27]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].I([O-])(=O)(=O)=[O:29].[Na+]>CO.O>[Cl:1][C:2]1[CH:3]=[C:4]([S:9]([CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]2[CH:16]=[CH:17][C:18]3[NH:23][C:22](=[O:24])[O:21][C:20]([CH3:25])([CH3:26])[C:19]=3[CH:27]=2)=[O:29])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: CC1(C)OC(=O)Nc2ccc(OCCCCSc3ccc(Cl)c(Cl)c3)cc21
Reactant: [O-][I+3]([O-])([O-])[O-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CC1(C)OC(=O)Nc2ccc(OCCCCS(=O)c3ccc(Cl)c(Cl)c3)cc21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
An amount of 2.14 gm (0.005 mol) of 6-[4-(3,4-dichlorophenyl-mercapto)-butoxy]-4,4-dimethyl-4H-3,1-benzoxazin-2-one is dissolved in 50 ml of methanol, mixed with a solution of 1.3 gm (0.06 mol) of sodium metaperiodate in 10 ml of water, and stirred for two hours at ambient temperature. Then, the mixture is refluxed for three hours, the volume of the reaction mixture is reduced by evaporation to about three-quarters, and water is added. The oil precipitated is separated by decanting of the solvent and is taken up in hot isopropanol/disiopropylether. Upon cooling, crystals are obtained which have a melting point of 138°-139° C.
Reaction SMILES: [NH:1](C(OCC1C=CC=CC=1)=O)[CH2:2][CH2:3][C:4](O)=[O:5].[CH2:17]([O:19][C:20](=[O:28])[C:21]1[CH:26]=[CH:25][C:24]([NH2:27])=[CH:23][CH:22]=1)[CH3:18]>>[CH2:17]([O:19][C:20](=[O:28])[C:21]1[CH:26]=[CH:25][C:24]([NH:27][C:4](=[O:5])[CH2:3][CH2:2][NH2:1])=[CH:23][CH:22]=1)[CH3:18]
Reactant: CCOC(=O)c1ccc(N)cc1
Reactant: O=C(O)CCNC(=O)OCc1ccccc1
Product: CCOC(=O)c1ccc(NC(=O)CCN)cc1

Procedure:
Z-beta-Ala-OH and ethyl-4-aminobenzoate according to 1.2., followed by deprotection according to 6.1. to give 4-(3-Amino-propionylamino)-benzoic acid ethyl ester, MS: 236 (M).
Reaction SMILES: FC(F)(F)S(O[C:7]1[C:8]([C:14]2[NH:15][C:16]3[C:21]([CH:22]=2)=[C:20]([F:23])[CH:19]=[CH:18][CH:17]=3)=[N:9][C:10]([Cl:13])=[N:11][CH:12]=1)(=O)=O.[CH2:26]([Sn](CCCC)(CCCC)C=C)[CH2:27]CC.[Li+].[Cl-]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:13][C:10]1[N:9]=[C:8]([C:14]2[NH:15][C:16]3[C:21]([CH:22]=2)=[C:20]([F:23])[CH:19]=[CH:18][CH:17]=3)[C:7]([CH:26]=[CH2:27])=[CH:12][N:11]=1
Reactant: O=S(=O)(Oc1cnc(Cl)nc1-c1cc2c(F)cccc2[nH]1)C(F)(F)F
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: C=Cc1cnc(Cl)nc1-c1cc2c(F)cccc2[nH]1
Temperature: 60 °C
Reaction time: 1 h
Yield: 72494.7 %

Procedure:
To a mixture of 2-chloro-4-(4-fluoro-1H-indol-2-yl)pyrimidin-5-yl trifluoromethanesulfonate (500 mg, 1.26 mmol), tributyl(vinyl)stannane (400 mg, 1.26 mmol) and anhydrous LiCl (150 mg, 3.54 mmol) in DMF (5 mL), Pd(PPh3)2Cl2 (50 mg, 0.07 mmol) was added under N2 protection. The reaction mixture was stirred at 60° C. for 1 h. Then it was concentrated in vacuo, and the residue was purified by column chromatography (PE:EA=10:1) to give the product of 2-(2-chloro-5-vinylpyrimidin-4-yl)-4-fluoro-1H-indole (250 g, yield: 72.3%). 1H-NMR (DMSO-d6, 400 MHz) δ 12.21 (br s, 1H), 8.85 (s, 1H), 7.41 (d, J=7.6 Hz, 1H), 7.21˜7.27 (m, 1H), 7.08˜7.20 (m, 2H), 6.87 (dd, J=10.4, 7.6 Hz, 1H), 6.01 (dd, J=17.6, 1.2 Hz, 1H), 5.72 (dd, J=11.2, 1.2 Hz, 1H). MS (M+H)+: 274/276.
Reaction SMILES: [C:1]([CH2:3][CH2:4][C:5]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:6][CH2:7][C:8](OCC)=[O:9])#[N:2].[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[NH2:2][CH2:1][CH2:3][CH2:4][C:5]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:6][CH2:7][CH2:8][OH:9]
Reactant: CCOC(=O)CCC(CCC#N)(c1ccccc1)c1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: NCCCC(CCCO)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
To a solution of ethyl 6-cyano-4,4-diphenyl-hexanoate (5.476 g) in anhydrous THF (195 mL) was added portionwise lithium aluminum hydride (LAH) (1.686 g). A large evolution of gas was observed. The mixture was stirred at rt for 1.5 hr. The reaction mixture was quenched by a careful addition of water (4.5 mL), followed by IN NaOH (4.5 mL) and additional water (15 niL). The mixture was stirred at rt for 10 min and then filtered and the solid was washed three times with THF. The organic filtrates were combined, dried (Na2SO4) and concentrated to give the desired product as a solid foam (4.56 g): MS showed (M+H)+ @ 284; 1H-NMR (CDCl3, δ): 1.05-1.3 (m, 4H), 2.0-2.20 (m, 4H), 2.30-2.42 (t, 2H), 2.82-3.0 (t, 2H), 3.0-3.25 (m, 2H), 3.50-3.65 (t, 2H), 5.10-5.20 (broad m, 1H), 6.86-7.36 (m, 14H).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[CH3:26])[CH2:9][C:10]([C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=2[F:19])=O)=[CH:4][CH:3]=1.Cl.[NH2:28][OH:29].C([O-])(O)=O.[Na+]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[CH3:26])[CH2:9]/[C:10](/[C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=2[F:19])=[N:28]\[OH:29])=[CH:4][CH:3]=1
Reactant: NO
Reactant: Cc1ccccc1C(CC(=O)c1cc(F)ccc1F)c1ccc(Br)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: Cc1ccccc1C(C/C(=N\O)c1cc(F)ccc1F)c1ccc(Br)cc1

Procedure:
In analogy to example 1, step 2, from 3-(4-bromo-phenyl)-1-(2,5-difluoro-phenyl)-3-o-tolyl-propan-1-one and hydroxylamine hydrochloride in the presence of NaHCO3 was prepared the title compound as a white foam, MS (ESI−): m/z=428.0 ([M−H]−, 1Br).
Reaction SMILES: [Cl:1][C:2]1[CH:20]=[CH:19][CH:18]=[CH:17][C:3]=1[C:4]([C:6]1[CH:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:7]=1[CH:13]=[CH:14][C:15]#[N:16])=[O:5].S([CH:31]([N+:33]#[C-])C)(C1C=CC(C)=CC=1)(=O)=O.[H-].[Na+].[CH3:37][CH2:38]OCC>CS(C)=O.O.Cl>[Cl:12][C:10]1[CH:9]=[CH:8][C:7]([C:13]2[C:14]([C:31]#[N:33])=[CH:15][NH:16][C:37]=2[CH3:38])=[C:6]([C:4](=[O:5])[C:3]2[CH:17]=[CH:18][CH:19]=[CH:20][C:2]=2[Cl:1])[CH:11]=1
Reactant: CCOCC
Reactant: N#CC=Cc1ccc(Cl)cc1C(=O)c1ccccc1Cl
Reactant: [C-]#[N+]C(C)S(=O)(=O)c1ccc(C)cc1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: Cc1[nH]cc(C#N)c1-c1ccc(Cl)cc1C(=O)c1ccccc1Cl
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of 33.9 g (0.11 mol) of 3-[2-(2-chlorobenzoyl)-4-chlorophenyl]-2-propenenitrile, 20 g (0.96 mol) of 1-tosylethyl isocyanide in 150 ml of dimethyl sulfoxide and 100 ml of ether was added dropwise to a suspension of 4.6 g (0.1 mol) of a 50% mineral oil dispension of sodium hydride in 100 ml of ether which was immersed in a room temperature water bath. Stirring at room temperature was continued for 2 hours. The mixture was diluted with 1.2 liters of water and 40 ml of 1 N hydrochloric acid and extracted with methylene chloride. The methylene chloride solution was washed with water, dried over anhydrous sodium sulfate and concentrated at reduced pressure to give a dark green oil. Crystallization from a mixture of ether and petroleum ether gave 4-[4-chloro-2-(2-chlorobenzoyl)phenyl]-5-methyl-1H-pyrrole-3-carbonitrile, mp 206°-208° C., as tan crystals. Recrystallization from ether gave the desired product as colorless crystals, mp 210°-211° C.