Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([NH:3][C:4]1[C:13]([CH3:14])=[CH:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([N+:15]([O-])=O)[CH:10]=2)[N:5]=1)[CH3:2]>CO.[Pt]=O>[CH2:1]([NH:3][C:4]1[C:13]([CH3:14])=[CH:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([NH2:15])[CH:10]=2)[N:5]=1)[CH3:2]
Reactant: CCNc1nc2ccc([N+](=O)[O-])cc2cc1C
Agent: O=[Pt]
Solvent: CO
Product: CCNc1nc2ccc(N)cc2cc1C
Reaction time: 1 h

Procedure:
The product (0.8 g) of Step B and platinum oxide on carbon (˜80 mg) was suspended in methanol. The resulting mixture was hydrogenated at 50 PSI for 1 h. The reaction mixture was filtered through filter aid and the solvent removed under vacuum to afford the product, which was used without further purification.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=O)([O-:3])=[O:2].[C:12]([O:18][CH2:19][CH2:20][N:21]([CH:39]1[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]1)[C:22](=[O:38])[CH2:23][CH2:24][CH2:25][O:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[NH:33][C:32](=[O:37])[CH:31]=[CH:30]2)(=[O:17])[CH2:13][C:14]([CH3:16])=[O:15]>N1C=CC=CC=1>[N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=[C:13]([C:14]([CH3:16])=[O:15])[C:12]([O:18][CH2:19][CH2:20][N:21]([CH:39]1[CH2:40][CH2:41][CH2:42][CH2:43][CH2:44]1)[C:22](=[O:38])[CH2:23][CH2:24][CH2:25][O:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[NH:33][C:32](=[O:37])[CH:31]=[CH:30]2)=[O:17])([O-:3])=[O:2]
Reactant: CC(=O)CC(=O)OCCN(C(=O)CCCOc1ccc2[nH]c(=O)ccc2c1)C1CCCCC1
Reactant: O=Cc1cccc([N+](=O)[O-])c1
Solvent: c1ccncc1
Product: CC(=O)C(=Cc1cccc([N+](=O)[O-])c1)C(=O)OCCN(C(=O)CCCOc1ccc2[nH]c(=O)ccc2c1)C1CCCCC1
Yield: 5.7 %

Procedure:
To 10 ml of pyridine were added 0.9 g of 3-nitrobenzaldehyde and 2.7 g of N-(2-acetoacetoxyethyl)-N-cyclohexyl-4-(6-carbostyriloxy)butyramide, and the mixture was heated at 90°-100° C. for 20 hours. After cooling the reaction mixture was extracted with chloroform, and the chloroform layer was washed with a saturated aqueous solution of potassium hydrogensulfate and with a saturated aqueous solution of sodium chloride, then was dried with anhydrous magnesium sulfate. After being concentrated, the residue was purified by a silica gen column chromatography (eluant: chloroform/methanol=100/1), then the eluate was dried under vacuum condition to yield 0.2 g of N-{2-[2-(3-nitrobenzyliden)acetoacetoxy]ethyl}-N-cyclohexyl-4-(6-carbostyriloxy)butyramide in the form a brown oily substance.
Reaction SMILES: [ClH:1].[C:2]([N:5]1[CH2:10][CH2:9][CH:8]([CH2:11][CH2:12][C:13]([OH:15])=[O:14])[CH2:7][CH2:6]1)(=[NH:4])[NH2:3].[CH3:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1O.C1(N=C=NC2CCCCC2)CCCCC1>N1C=CC=CC=1>[ClH:1].[C:2]([N:5]1[CH2:10][CH2:9][CH:8]([CH2:11][CH2:12][C:13]([O:15][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[CH3:16])=[O:14])[CH2:7][CH2:6]1)(=[NH:3])[NH2:4]
Reactant: N=C(N)N1CCC(CCC(=O)O)CC1
Reactant: Cc1ccccc1O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Solvent: c1ccncc1
Product: Cc1ccccc1OC(=O)CCC1CCN(C(=N)N)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 54 %

Procedure:
A mixture of 4 g of 1-amidino-4-piperidinepropionic acid hydrochloride, 1.9 of o-methylphenol, 3.5 g of dicyclohexylcarbodiimide and 20 ml of dry pyridine was stirred overnight at room temperature. Any insoluble materials were filtered and washed with pyridine. The filtrate and washings were combined together, and the solvent was removed under reduced pressure. Ethyl acetate and ether were added to the residue to give crystals. After being air-dried, the crystals were recrystallized from water to obtain 3 g (yield: 54%) of -methylphenyl 1-amidino-4-piperidinepropionate hydrochloride as colorless prisms having a melting point of 184° to 185.5° C. The IR and NMR spectra of the compound were identical with those of the compound obtained in Example 28.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[C:4]([N+:11]([O-])=O)[CH:3]=1.[NH4+].[Cl-]>CCO.O.[Fe]>[NH2:11][C:4]1[CH:3]=[C:2]([CH3:1])[CH:10]=[CH:9][C:5]=1[C:6]([NH2:8])=[O:7]
Reactant: Cc1ccc(C(N)=O)c([N+](=O)[O-])c1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: Cc1ccc(C(N)=O)c(N)c1
Yield: 90 %

Procedure:
The title compound was prepared following the procedure described in Step 3 of Intermediate-1 using 4-methyl-2-nitrobenzamide (1.60 g, 8.88 mmol), iron powder (2.97 g, 53.33 mmol), and NH4Cl (2.85 g, 53.33 mmol) in EtOH (8 mL) and water (2 mL) to afford 1.2 g of the title product. 1H NMR (300 MHz, DMSO-d6): δ 7.62 (br s, 1H), 7.42 (d, J=7.8 Hz, 1H), 6.93 (br s, 1H), 6.53 (s, 2H), 6.46 (s, 1H), 6.29 (d, J=7.8 Hz, 1H), 2.15 (s, 3H).
Reaction SMILES: CC(C)([O-])C.[K+].[CH2:7]([OH:10])[CH2:8][OH:9].[C:11]1([CH:21]2[CH2:23][O:22]2)[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1>C(OCC)(=O)C>[OH:9][CH2:8][CH2:7][O:10][CH2:23][CH:21]([C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1)[OH:22]
Reactant: OCCO
Reactant: c1ccc2c(C3CO3)cccc2c1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Product: OCCOCC(O)c1cccc2ccccc12
Temperature: 80 °C
Reaction time: 1 h

Procedure:
A mixture of 4.5 g of potassium tert-butoxide and 45 ml of ethylene glycol was heated to 80° C. Thereto was dropwise added 13.7 g of 2-(1-naphthyl)oxirane in 1 hour. The resulting mixture was stirred for 1 hour at the same temperature. The reaction mixture was cooled and added to a mixture of 50 ml of ethyl acetate and 50 ml of ice water. The organic layer was separated. The aqueous layer was extracted twice each with 20 ml of ethyl acetate. The extracts were combined with the previously separated organic layer. The combined organic layer was washed with water and a saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue thus obtained was purified by column chromatography (eluant:toluene/ethyl acetate=1/3) to obtain 8.3 g of 2-(2-hydroxyethoxy)-1-(1-naphthyl)ethanol.
Reaction SMILES: Cl[C:2]1(Cl)[C:5](=[O:6])[CH2:4][CH:3]1[CH2:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10].[Cl-].[NH4+].CO>CCOCC.[Zn]>[O:6]=[C:5]1[CH2:2][CH:3]([CH2:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:4]1
Reactant: CCOC(=O)CCC1CC(=O)C1(Cl)Cl
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: CO
Solvent: CCOCC
Product: CCOC(=O)CCC1CC(=O)C1
Temperature: 25 °C
Yield: 60.1 %

Procedure:
A solution of ethyl 3-(2,2-dichloro-3-oxocyclobutyl)propanoate (10.49 g, 43.87 mmol) and ammonium chloride (12 g, 220 mmol) in methanol (310 mL, 7600 mmol) was treated in small portions with zinc powder (14 g, 220 mmol). The reaction mixture was heated at reflux for 3 h after which time GC indicated the reaction was complete. The reaction mixture was cooled to room temperature and was filtered through Celite, washing the pad with Et2O. The filtrate was concentrated in vacuo to afford pale yellow solution. The solution was diluted with 200 mL Et2O and washed with 100 mL water. The separated aqueous layer was back extracted with 100 mL Et2O and the combined organic phase was washed with 100 mL 1:1 water/brine, 50 mL water, and 150 mL saturated aqueous NaHCO3. The organic layer was dried over MgSO4, filtered and concentrated in vacuo to afford the title compound (4.49 g, 60%) as a pale yellow oil which was of sufficient purity for use in the next step: GC purity >95% (ret. time, 4.24 min).
Reaction SMILES: ClC(OC(Cl)C)=O.[CH3:8][C:9]12[CH2:23][CH:18]([N:19](C)[CH2:20][CH2:21]1)[CH2:17][CH2:16][C:15]1[C:10]2=[CH:11][CH:12]=[CH:13][CH:14]=1.C([O-])(O)=O.[Na+].ClCCl>ClCCCl>[CH3:8][C:9]12[CH2:23][CH:18]([NH:19][CH2:20][CH2:21]1)[CH2:17][CH2:16][C:15]1[C:10]2=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: CN1CCC2(C)CC1CCc1ccccc12
Agent: CC(Cl)OC(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: ClCCCl
Product: CC12CCNC(CCc3ccccc31)C2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1-Chloroethyl chloroformate (3.8 mL) is added dropwise to a mixture of 1,11-dimethyl-11-aza-tricyclo[8.3.1.0*2,7*]tetradeca-2,4,6-triene (0.75 g) and NaHCO3 (2.9 g) in 1,2-dichloroethane (3.5 mL) chilled in an ice bath. The reaction mixture is warmed to room temperature in the cooling bath and stirred overnight. Then, dichloromethane (20 mL) is added and the precipitate is removed by filtration. The filtrate is concentrated under reduced pressure and the residue is dissolved in methanol (20 mL). The resulting solution is stirred at reflux temperature for 2 h. The solution is concentrated and the residue is purified by HPLC on reversed phase (water/MeCN/NH3) to give the title compound.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]1[O:10][C:9](=[O:11])[N:8]([CH3:12])[CH2:7]1.Cl.Cl.[N:15]1[CH:20]=[CH:19][CH:18]=[N:17][C:16]=1[N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(O)CCC>[CH3:12][N:8]1[CH2:7][CH:6]([CH2:5][CH2:4][CH2:3][CH2:2][N:24]2[CH2:25][CH2:26][N:21]([C:16]3[N:15]=[CH:20][CH:19]=[CH:18][N:17]=3)[CH2:22][CH2:23]2)[O:10][C:9]1=[O:11]
Reactant: CN1CC(CCCCCl)OC1=O
Reactant: c1cnc(N2CCNCC2)nc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: CCCCO
Product: CN1CC(CCCCN2CCN(c3ncccn3)CC2)OC1=O
Yield: 35.8 %

Procedure:
Following the procedure of Example 1, mixture of 5-(4-chlorobutyl)-3-methyl-2-oxazolidinone (5.0 g, 0.0262 mol), 1-(2-pyrimidinyl)piperazine dihydrochloride (6.62 g, 0.0279 mol), potassium carbonate (19.3 g, 0.140 mol) and potassium iodide (0.75 g) in 1-butanol (75 ml) gave an oil (3.0 g) which crystallized upon standing. Recrystallization from ethyl acetate/light pet ether followed by drying under high vacuum gave 1.33 g (16% yield), mp 74°-76° C.
Reaction SMILES: C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[CH2:7]1)=[O:5])C.[CH3:22][Si]([N-][Si](C)(C)C)(C)C.[Li+].IC>C1COCC1>[CH2:15]([O:14][C:12]([N:8]1[CH2:9][CH2:10][CH2:11][C:6]([CH3:22])([C:4]([OH:3])=[O:5])[CH2:7]1)=[O:13])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Reactant: CCOC(=O)C1CCCN(C(=O)OCc2ccccc2)C1
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CI
Product: CC1(C(=O)O)CCCN(C(=O)OCc2ccccc2)C1
Temperature: 25 °C
Reaction time: 0.58 h

Procedure:
To a −78° C. solution of the product of Example 45A (6.0 g, 20.6 mmoles) in THF (50 mL) was added a solution of lithium bis(trimethylsilyl)amide (1.0 M in THF, 22.7 mmoles). After 35 min, iodomethane (1.4 mL, 22.7 mmoles) was added and the reaction was slowly warmed to room temperature and stirred overnight. The reaction was quenched with aqueous sat. ammonium chloride and extracted with Et2O. The organic layer was then rinsed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography employing a solvent gradient (hexane→65:35 hexane:EtOAc). The resulting ester was hydrolyzed overnight at room temperature in THF (15 mL), H2O (10 mL), and EtOH (15 mL) with NaOH (2.5 g). The solution was concentrated under vacuum; the residue was dissolved in saturated ammonium chloride: and, the solution was extracted with ethyl acetate (3×). The combined ethyl acetate extracts were dried over sodium sulfate, filtered, and concentrated under vacuum to yield the title compound as a white solid.
Reaction SMILES: [CH2:1]1[C:7]2=[C:8]3[C:12](=[CH:13][CH:14]=[C:6]2[O:5][CH2:4][CH2:3][N:2]1C(OC(C)(C)C)=O)[NH:11][CH:10]=[CH:9]3.[H-].[Na+].CN(C=O)C.[CH:29]([C:32]1[CH:37]=[CH:36][C:35]([S:38](Cl)(=[O:40])=[O:39])=[CH:34][CH:33]=1)([CH3:31])[CH3:30]>N.CO>[CH:29]([C:32]1[CH:37]=[CH:36][C:35]([S:38]([N:11]2[C:12]3[C:8](=[C:7]4[CH2:1][NH:2][CH2:3][CH2:4][O:5][C:6]4=[CH:14][CH:13]=3)[CH:9]=[CH:10]2)(=[O:40])=[O:39])=[CH:34][CH:33]=1)([CH3:31])[CH3:30]
Reactant: CC(C)c1ccc(S(=O)(=O)Cl)cc1
Reactant: CC(C)(C)OC(=O)N1CCOc2ccc3[nH]ccc3c2C1
Agent: N
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CO
Product: CC(C)c1ccc(S(=O)(=O)n2ccc3c4c(ccc32)OCCNC4)cc1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 15.7 %

Procedure:
tert-Butyl 1,3,4,8-tetrahydro-2H-[1,4]oxazepino[6,7-e]indole-2-carboxylate (Intermediate 18, 14 mg, 0.050 mmol), NaH (60% in mineral oil, 6.4 mg, 0.10 mmol) and dry DMF (0.2 mL) were shaken at room temperature for 10 minutes. 4-Isopropylbenzenesulfonyl chloride (22 mg, 0.10 mmol, in 0.15 mL of dry DMF) was added to the solution. The reaction mixture was shaken at room temperature for another 20 minutes and a mixture of MeOH/1 M HCl (3:1, 1 mL) was added. The reaction mixture was stirred overnight and evaporated. The residue was dissolved in 1 M NH3 in MeOH (1 mL, 1 mmol) and MeOH (1 mL). The crude product was purified by preparative HPLC (XTerra C18, 50 mM NH4HCO3 pH 10-CH3CN) to give the title compound as an off-white solid (2.9 mg). MS m/z 371 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][C:15]#[CH:16])[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.[F:19][C:20]1[CH:26]=[C:25](I)[CH:24]=[CH:23][C:21]=1[NH2:22]>C(N)CCC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:22][C:21]1[CH:23]=[CH:24][C:25]([C:16]#[C:15][CH2:14][CH2:13][N:10]2[CH2:9][CH2:8][CH:7]([CH2:6][C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:18][CH:17]=3)[CH2:12][CH2:11]2)=[CH:26][C:20]=1[F:19]
Reactant: C#CCCN1CCC(Cc2ccc(Cl)cc2)CC1
Reactant: Nc1ccc(I)cc1F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCCCN
Product: Nc1ccc(C#CCCN2CCC(Cc3ccc(Cl)cc3)CC2)cc1F
Yield: 17.6 %

Procedure:
To a solution of 4-(4-chlorobenzyl)-1-(but-3-yn-1-yl)piperidine (400 mg, 1.53 mmol) and 2-fluoro-4-iodoaniline (436 mg, 1.84 mmol) in 10 mL of butylamine is added 70 mg of Pd(PPh3)4. The resulting solution is allowed to reflux for 24 hr. The solvent is evaporated in vacuo and the residue is purified by flash chromatography giving the title product as a brown oil (100 mg, 18%): 1H NMR (CDCl3) 1.25 (m, 2 H), 1.46 (m, 1 H), 1.58 (m, 2 H), 1.97 (m, 2 H), 2.56 (m, 6 H), 2.88 (m, 2 H), 3.83 (bs, 2 H), 6.62 (m, 1 H), 6.80-7.24 (m, 6 H).
Reaction SMILES: F[C:2]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:3]=1[NH2:4].O.O.O.O.O.O.O.O.O.[S-2:21].[Na+].[Na+].C(=O)(O)[O-].[Na+].O>ClCCl>[NH2:4][C:3]1[CH:5]=[C:6]([N+:9]([O-:11])=[O:10])[CH:7]=[CH:8][C:2]=1[SH:21]
Reactant: [S-2]
Reactant: Nc1cc([N+](=O)[O-])ccc1F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: Nc1cc([N+](=O)[O-])ccc1S
Temperature: 125 °C
Yield: 100.8 %

Procedure:
2-Fluoro-5-nitroaniline (1 g, 6.41 mmol), sodium sulfide nonahydrate (1.7 g, 7.05 mmol), sodium bicarbonate (600 mg, 7.05 mmol) and water (15 mL) were combined and heated in the microwave at 125° C. for 5 min. After cooling, dichloromethane was added, and the organic layer was washed with 2M aqueous hydrochloric acid and then brine. The combined organic layers were dried over anhydrous MgSO4 and evaporated to afford 1.1 g (33%) of the title compound.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([CH:42]=[C:43]([C:46]([CH3:49])([CH3:48])[CH3:47])[C:44]=1[OH:45])[CH2:8][C:9]([CH2:26][C:27]1[CH:32]=[C:31]([C:33]([CH3:36])([CH3:35])[CH3:34])[C:30]([OH:37])=[C:29]([C:38]([CH3:41])([CH3:40])[CH3:39])[CH:28]=1)([C:23]([CH3:25])=[O:24])[C:10]([O:12][CH:13]1[CH2:18][C:17]([CH3:20])([CH3:19])[NH:16][C:15]([CH3:22])([CH3:21])[CH2:14]1)=[O:11])([CH3:4])([CH3:3])[CH3:2].[C:50](OC(=O)C)(=[O:52])[CH3:51]>>[C:33]([C:31]1[CH:32]=[C:27]([CH:28]=[C:29]([C:38]([CH3:41])([CH3:40])[CH3:39])[C:30]=1[OH:37])[CH2:26][C:9]([CH2:8][C:7]1[CH:42]=[C:43]([C:46]([CH3:49])([CH3:48])[CH3:47])[C:44]([OH:45])=[C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])[CH:6]=1)([C:23]([CH3:25])=[O:24])[C:10]([O:12][CH:13]1[CH2:14][C:15]([CH3:22])([CH3:21])[N:16]([C:50](=[O:52])[CH3:51])[C:17]([CH3:20])([CH3:19])[CH2:18]1)=[O:11])([CH3:36])([CH3:35])[CH3:34]
Reactant: CC(=O)OC(C)=O
Reactant: CC(=O)C(Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1)(Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1)C(=O)OC1CC(C)(C)NC(C)(C)C1
Product: CC(=O)N1C(C)(C)CC(OC(=O)C(Cc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)(Cc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)C(C)=O)CC1(C)C

Procedure:
A solution of 2,2,6,6-tetramethyl-4-piperidinyl 2,2-bis-(3,5-di-tert-butyl-4-hydroxybenzyl)-acetoacetate (Example 1, 10.0 g; 0.015 mol) in 100 ml of acetic anhydride is stirred for 20 hours at 100°. The mixture is concentrated in vacuo. After recrystallisation from hexane/toluene, the product is filtered off and 8.41 g of 1-acetyl-2,2,6,6-tetramethyl-4-piperidinyl 2,2-bis-(3,5-di-tert-butyl-4-hydroxybenzyl)-acetoacetate, melting point 165°-166° C. (compound 22), are obtained.
Reaction SMILES: [CH3:1][N:2]1[C:7](=[O:8])[C:6]2=[CH:9][NH:10][N:11]=[C:5]2[N:4]([CH2:12][C:13]([CH3:16])([CH3:15])[CH3:14])[C:3]1=[O:17].Br[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]2[CH:30]=[N:29][CH:28]=[N:27]2)=[CH:22][CH:21]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[N:26]1([C:23]2[CH:24]=[CH:25][C:20]([CH2:19][N:10]3[CH:9]=[C:6]4[C:5]([N:4]([CH2:12][C:13]([CH3:14])([CH3:16])[CH3:15])[C:3](=[O:17])[N:2]([CH3:1])[C:7]4=[O:8])=[N:11]3)=[CH:21][CH:22]=2)[CH:30]=[N:29][CH:28]=[N:27]1
Reactant: BrCc1ccc(-n2cncn2)cc1
Reactant: Cn1c(=O)c2c[nH]nc2n(CC(C)(C)C)c1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cn1c(=O)c2cn(Cc3ccc(-n4cncn4)cc3)nc2n(CC(C)(C)C)c1=O
Temperature: 25 °C
Reaction time: 5 h
Yield: 101.1 %

Procedure:
5-methyl-7-neopentyl-2H-pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-dione (200 mg, 0.847 mmol), 1-(4-(bromomethyl)phenyl)-1H-1,2,4-triazole (202 mg, 0.847 mmol) and K2CO3 (117 mg, 0.847 mmol) are suspended in 5 mL of anhydrous DMF. The reaction mixture is stirred at room temperature for 5 h, and then evaporated to dryness under reduced pressure. The residue is treated with water, and then extracted with dichloromethane three times. The combined organic phase is dried with anhydrous sodium sulfate, filtered, and then evaporated to dryness to give 337 mg of crude product, which is used in the next step without further purification. MS (ESI) m/z 394.2 [M+H]+.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH:6]=[CH2:7].II.[CH3:15][C:16]1[CH:17]=[CH:18][C:19]([S:22]([NH:25]Cl)(=[O:24])=[O:23])=[CH:20][CH:21]=1>C(#N)C.O>[S:22]([N:25]1[CH2:7][CH:6]1[C:5]1[CH:8]=[CH:9][CH:10]=[C:3]([C:2]([F:11])([F:12])[F:1])[CH:4]=1)([C:19]1[CH:20]=[CH:21][C:16]([CH3:15])=[CH:17][CH:18]=1)(=[O:24])=[O:23]
Reactant: Cc1ccc(S(=O)(=O)NCl)cc1
Reactant: C=Cc1cccc(C(F)(F)F)c1
Agent: II
Solvent: CC#N
Solvent: O
Product: Cc1ccc(S(=O)(=O)N2CC2c2cccc(C(F)(F)F)c2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 87.6 %

Procedure:
3-(Trifluoromethyl)styrene (1.70 mL, 11.5 mmol) is added to a mixture of iodine (0.29 g, 1.15 mmol) and Chloramine-T (3.12 g, 11.5 mmol) in acetonitrile (35 mL). The reaction mixture is stirred at room temperature under a nitrogen atmosphere overnight, then taken in H2O (200 mL) and extracted with CH2Cl2 (3×100 mL). The combined organic layer is washed with brine, dried over MgSO4, concentrated and purified by silica gel chromatography (0˜20% EtOAc/Hexanes) to provide 1-tosyl-2-(3-(trifluoromethyl)phenyl)aziridine (3.44 g, 88% yield) as a colorless oil product.
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([C:19]([O:21][CH3:22])=[O:20])[C:7]2[NH:8][C:9]3[CH:10]=[C:11]([O:17][CH3:18])[CH:12]=[CH:13][C:14]=3[C:15]=2[N:16]=1.[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C1COCC1.CCOC(C)=O>[CH2:23]([N:8]1[C:9]2[CH:10]=[C:11]([O:17][CH3:18])[CH:12]=[CH:13][C:14]=2[C:15]2[N:16]=[C:4]([Br:3])[CH:5]=[C:6]([C:19]([O:21][CH3:22])=[O:20])[C:7]1=2)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: BrCc1ccccc1
Reactant: COC(=O)c1cc(Br)nc2c1[nH]c1cc(OC)ccc12
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COC(=O)c1cc(Br)nc2c3ccc(OC)cc3n(Cc3ccccc3)c12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 23.1 %

Procedure:
Sodium hydride (81 mg, 2 0 mmol) was added to a solution of methyl 2-bromo-7-methoxy-5H-pyrido[3,2-b]indole-4-carboxylate (450 mg, 1.34 mmol) in THF (6 mL) in an ice bath. After 20 min this was removed from the bath and left stirring at RT for 0.5 h. Benzyl bromide (276 mg, 1.61 mmol) was added. After stirring at RT for 3 days, this was diluted with EtOAc, washed with water, brine, and dried over Na2SO4 Removal of the solvent followed by radial chromatography (elution with DCM) afforded methyl 5-benzyl-2-bromo-7-methoxy-5H-pyrido[3,2-b]indole-4-carboxylate (130 mg, 0.31 mmol, 23% yield). MS (ESI) m/z 425.0 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 8.27 (1H, d, J=8.55 Hz), 7.59 (1H, s), 7.17-7.24 (3H, m), 6.97 (1H, dd, J=8.70, 1.98 Hz), 6.88-6.93 (2H, m), 6.84 (1H, d, J=1.83 Hz), 5.67 (2H, s), 3.86 (3H, s), 3.70 (3H, s).
Reaction SMILES: [Br-].[O:2]1[CH2:6][CH2:5][O:4][CH:3]1[CH2:7][CH2:8][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[K+].[CH3:34][C:35]1[CH:36]=[C:37]([CH:40]=[CH:41][C:42]=1[CH3:43])[CH:38]=O.[Cl-].[NH4+]>O1CCCC1.CO.[C].[Pd].C(OCC)(=O)C>[O:4]1[CH2:5][CH2:6][O:2][CH:3]1[CH2:7][CH2:8][CH2:38][C:37]1[CH:40]=[CH:41][C:42]([CH3:43])=[C:35]([CH3:34])[CH:36]=1
Reactant: c1ccc([P+](CCC2OCCO2)(c2ccccc2)c2ccccc2)cc1
Reactant: Cc1ccc(C=O)cc1C
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: [Br-]
Solvent: CCOC(C)=O
Solvent: CO
Solvent: C1CCOC1
Product: Cc1ccc(CCCC2OCCO2)cc1C
Reaction time: 0.5 h
Yield: 89 %

Procedure:
[2-(1,3-Dioxolan-2-yl)ethyl]triphenylphosphonium bromide (99.2 g, 224 inmol) was suspended in tetrahydrofuran (200 mL) and a solution of potassium t-butoxide (25.1 g, 224 mmol) in tetrahydrofuran (200 mL) was added thereto under nitrogen atmosphere over 30 minutes, followed by stirring of the mixture under ice-cooling for 30 minutes. A solution of 3,4-dimethylbenzaldehyde (20.2 g, 151 mmol) in tetrahydrofuran (100 mL) was added thereto over 20 minutes and the mixture was stirred under ice-cooling for 20 minutes. A saturated aqueous ammonium chloride solution and ethyl acetate were added to the reaction mixture to separate it. The thus obtained organic phase was separated, washed with water and a saturated aqueous NaCl solution and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure and the residue was purified by silica gel chromatography (hexane:ethyl acetate, 15:1-10:1) to obtain a crude product (29.9 g). 10% Palladium-carbon (3.01 g, 50% hydrous) was added to a solution of the obtained crude product (29.9 g) in methanol (300 mL) and the mixture was stirred at room temperature under hydrogen atmosphere for 2 hours. After the palladium-carbon in the reaction mixture was Celite-filtered, the filtrate was evaporated under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate, 10:1) to obtain [1-(1,3-dioxolan-2-yl)-3-(3,4-dimethylphenyl)propane (29.6 g, yield: 98%). Water (250 mL) -was added to a solution of the obtained [1-(1,3-dioxolan-2-yl)-3-(3,4-dimethylphenyl)]propane (29.6 g, 134.4 mmol) in tetrahydrofuran (250 mL) and OXONE™ (248 g, 403 mmol) was added thereto with stirring at room temperature over 20 minutes, followed by stirring of the mixture at room temperature for 18 hours. The insolubles were separated by filtration and a 1N aqueous sodium hydroxide solution was added thereto to bring the pH to 11. Ether was added thereto to separate it. A 1N aqueous hydrochloric acid solution was added to an aqueous phase to bring the pH to 2 and ethyl acetate was added thereto to separate it. The thus obtained organic phase was separated, washed with water and a saturated aqueous NaCl solution and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure to obtain the title compound (26.1 g, yield: 98%).