Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[Cl:8].[CH3:9][Si:10]([C:13]#[CH:14])([CH3:12])[CH3:11].Cl>C(N(CC)CC)C.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:14]#[C:13][Si:10]([CH3:12])([CH3:11])[CH3:9]
Reactant: Clc1ccccc1Br
Reactant: C#C[Si](C)(C)C
Agent: [Cu]I
Agent: Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Product: C[Si](C)(C)C#Cc1ccccc1Cl
Temperature: 25 °C
Yield: 99.3 %

Procedure:
2-Bromochlorobenzene (54.1 ml, 0.46 mol) and trimethylsilylacetylene (72 ml, 0.51 mol) were dissolved in triethylamine (250 ml). Triphenylphosphine (0.4 g, 1.5 mmol), copper (I) iodide (0.3 g, 1.6 mmol) and bistriphenyphosphinepalladium (II) dichloride (0.5 g, 0.67 mmol) were added and the mixture was heated under reflux for 18 h. The reaction mixture was cooled to ambient temperature and carefully added to 10% hydrochloric acid (480 ml). The product was extracted into hexane (3×200 ml), the extracts were washed with 10% hydrochloric acid (200 ml) and water (2×200 ml) then dried (MgSO4) and evaporated in vacuo to give (2-chlorophenylethynyl)-trimethylsilane (95.4 g) as an orange oil, which was used without further purification.
Reaction SMILES: [C:1]1([C:7]2[N:8]=[C:9]([S:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][NH:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[NH:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:32]1([N:38]=[C:39]=[O:40])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>CCCCCC>[C:1]1([C:7]2[N:8]=[C:9]([S:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][N:24]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[C:39]([NH:38][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[O:40])[NH:10][C:11]=2[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCCCCCCNCCCCCSc1nc(-c2ccccc2)c(-c2ccccc2)[nH]1
Reactant: O=C=Nc1ccccc1
Solvent: CCCCCC
Product: CCCCCCCN(CCCCCSc1nc(-c2ccccc2)c(-c2ccccc2)[nH]1)C(=O)Nc1ccccc1
Yield: 375 %

Procedure:
To a solution of N-[5-(4,5-diphenyl-1H-imidazol-2-ylthio)pentyl]-1-heptanamine (1.0 g, 0.0024 mol) in hexane (50 mL) was added, dropwise, a solution of phenylisocyanate (0.27 mL, 0.298 g, 0.0025 mol) in hexane (25 mL) and the reaction mixture was stirred at ambient temperature for 4 hours. The reaction mixture was concentrated under vacuum and the residue was chromatographed with 6:4 hexane-ethyl acetate to give the title compound (0.5 g, 0.009 mol) as a yellow amorphous solid. 1H NMR (CDCl3) δ 11.0(s,1H), 7.7-6.9(m,14H), 6.4(s,1H), 3.4(t,2H,J=7 Hz), 3.2(t,2H,J=7 Hz), 3.0(t,2H,J=7 Hz), 1.9-1.1(m,16H), 0.9(t,3H,J=8 Hz).
Reaction SMILES: B.[CH:2]([C:5]1[CH:6]=[CH:7][C:8]([O:24][CH3:25])=[C:9]([C:11]2[C:12]([C:21](O)=[O:22])=[CH:13][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:15][CH:16]=2)[CH:10]=1)([CH3:4])[CH3:3].C(C1C=CC(OC)=C(C2C(C(N)=O)=CC(C(F)(F)F)=CC=2)C=1)(C)C>C1COCC1>[CH:2]([C:5]1[CH:6]=[CH:7][C:8]([O:24][CH3:25])=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:18])([F:19])[F:20])=[CH:13][C:12]=2[CH2:21][OH:22])[CH:10]=1)([CH3:4])[CH3:3]
Reactant: COc1ccc(C(C)C)cc1-c1ccc(C(F)(F)F)cc1C(=O)O
Agent: B
Agent: COc1ccc(C(C)C)cc1-c1ccc(C(F)(F)F)cc1C(N)=O
Solvent: C1CCOC1
Product: COc1ccc(C(C)C)cc1-c1ccc(C(F)(F)F)cc1CO
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A solution of borane in THF (1 M, 859 μL, 0.859 mmol) was added dropwise to a stirred solution of 5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-carboxylic acid and 5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-carboxamide (3:1, 96.8 mg, 0.286 mmol) in dry THF at room temperature under N2. The reaction was stirred at room temperature for 3 h and carefully quenched with water (10 mL). The mixture was extracted with EtOAc (3×20 mL) and the combined extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 125×160 mm, 0-30% EtOAc in hexanes gradient) to afford [5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanol as a colorless oil. Rf=0.27 (10% EtOAc/hexanes). 1H NMR (CDCl3, 500 MHz) δ 7.89 (br s, 1H), 7.62 (dd, J=8.0, 1.3 Hz, 1H), 7.36 (d, J=8.0 Hz, 1H), 7.29 (dd, J=8.5, 2.3 Hz, 1H), 7.03 (d, J=2.3 Hz, 1H), 6.96 (d, J=8.5, 1H), 4.51 (m, 2H), 3.74 (s, 3H), 2.93 (septet, J=7.0 Hz, 1H), 2.51 (s, 1H), 1.29 (d, J=7.0 Hz, 6H).
Reaction SMILES: [NH2:1][C:2]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].[CH:12]([NH2:14])=O>O>[CH3:11][C:10]1[CH:9]=[CH:8][CH:7]=[C:3]2[C:2]=1[N:1]=[CH:12][NH:14][C:4]2=[O:5]
Reactant: NC=O
Reactant: Cc1cccc(C(=O)O)c1N
Solvent: O
Product: Cc1cccc2c(=O)[nH]cnc12

Procedure:
6 g of 2-amino 3 methyl benzoic acid and 8 ml formamide were heated at 170° C. for 1.5 hours. Water was added and solid filtered to provide 4.6 g of 8-methyl 4-quinazolinone as a white solid, mp-260° C. NMR acetone d6 δ 8.14(1H,br,S), 8.06(1H,m), 7.66(1H,m), 7.38(1H,m), 2.58(3H,S).
Reaction SMILES: [C-:1]#[N:2].[K+].Cl[C:5]1[S:6][C:7]2[CH:13]=[C:12]([NH:14][CH:15]([CH3:17])[CH3:16])[CH:11]=[CH:10][C:8]=2[N:9]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CS(C)=O>[C:1]([C:5]1[S:6][C:7]2[CH:13]=[C:12]([NH:14][CH:15]([CH3:17])[CH3:16])[CH:11]=[CH:10][C:8]=2[N:9]=1)#[N:2]
Reactant: [C-]#N
Reactant: CC(C)Nc1ccc2nc(Cl)sc2c1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CC(C)Nc1ccc2nc(C#N)sc2c1
Temperature: 120 °C

Procedure:
Potassium cyanide (18 mg) and 2-chloro-6-isopropylaminobenzothiazole (18 mg) were dissolved in 1 ml DMSO and heated to 120° C. for 4 h. After cooling to room temperature, the reaction was poured into 0.2M potassium phosphate, pH 4.5. The aqueous layer was extracted with ethyl acetate three times, washed with water, and dried over sodium sulfate. The solvent was removed by rotary evaporation and the residue purified by silica gel chromatography (20% ethyl acetate in hexanes). 1H-NMR (d6-DMSO): δ 7.83 (d, 1H, J=9.2 Hz), 7.15 (d, 1H, J=2.4 Hz), 6.97 (dd, 1H, J=2.4, 8.8 Hz), 6.52 (bd, 1H, J=7.2 Hz), 3.61 (m, 1H), 1.15 (d, 6H, J=6 Hz).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]2[C:4]=1[C:5](=[O:27])[NH:6][C:7]([C:15]1[CH:20]=[CH:19][C:18]([N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)=[CH:17][CH:16]=1)=[N:8]2.CCN(CC)CC.[CH:35]1([C:38](Cl)=[O:39])[CH2:37][CH2:36]1>C(Cl)Cl>[CH:35]1([C:38]([N:24]2[CH2:23][CH2:22][N:21]([C:18]3[CH:19]=[CH:20][C:15]([C:7]4[NH:6][C:5](=[O:27])[C:4]5[C:9](=[CH:10][C:11]([O:13][CH3:14])=[CH:12][C:3]=5[O:2][CH3:1])[N:8]=4)=[CH:16][CH:17]=3)[CH2:26][CH2:25]2)=[O:39])[CH2:37][CH2:36]1
Reactant: COc1cc(OC)c2c(=O)[nH]c(-c3ccc(N4CCNCC4)cc3)nc2c1
Reactant: O=C(Cl)C1CC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1cc(OC)c2c(=O)[nH]c(-c3ccc(N4CCN(C(=O)C5CC5)CC4)cc3)nc2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 63.9 %

Procedure:
To a solution of 5,7-dimethoxy-2-(4-(piperazin-1-yl)phenyl)quinazolin-4(3H)-one (0.150 g, 0.40 mmol) in CH2Cl2 (10 mL) was added Et3N (0.08 mL, 0.60 mmol), and cyclopropane carbonyl chloride (0.03 mL, 0.36 mmol). The resulting solution was stirred overnight at room temperature. The solution was concentrated in vacuo and the material was purified by flash chromatography on silica gel eluting with 0% to 50% of 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2 to afford the title compound (0.100 g, 63%). 1H NMR (300 MHz, DMSO-d6): δ 11.78 (s, 1H), 8.12 (d, J=8.9 Hz, 2H), 7.04 (d, J=9.2 Hz, 2H), 6.63-6.74 (m, 1H), 6.39-6.52 (m, 1H), 3.73-3.95 (m, 8H), 3.51-3.73 (m, 2H), 3.21-3.49 (m, 4H), 1.93-2.10 (m, 1H), 0.56-0.83 (m, 4H). APCI MS m/z 435 [M+H]+.
Reaction SMILES: C([N-]C(C)C)(C)C.[Li+].[N:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=1.[Cl:16][C:17]1[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][C:18]=1[C:19](OC)=[O:20]>C1COCC1>[Cl:16][C:17]1[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][C:18]=1[C:19](=[O:20])[CH2:15][C:11]1[CH:10]=[N:9][CH:14]=[CH:13][CH:12]=1
Reactant: COC(=O)c1cccc(Cl)c1Cl
Reactant: Cc1cccnc1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: O=C(Cc1cccnc1)c1cccc(Cl)c1Cl
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 13.4 %

Procedure:
To lithium diisopropyl amide (20 mL, 1.5 M in cyclohexane, 30 mmol) in THF (50.0 mL) at −78° C. was added a solution of 3-picoline (2.79 g, 30 mmol) in THF (25.0 mL) drop wise and stirred at −78° C. for 0.5 hours. The dry ice bath was removed and the reaction mixture was stirred at room temperature 1 hour. The mixture was then cooled to 0° C. and a solution of methyl 2,3-dichlorobenzoate (6.15 g, 30 mmol) in THF (25.0 mL) was added drop wise. The reaction mixture was warmed to room temperature and stirred overnight. The reaction was quenched with ammonium chloride and extracted with ethyl acetate (2×). Combined ethyl acetate phase was washed with brine, dried over magnesium sulfate and concentrated. Purification by chromatography on silica gel (70% ethyl acetate/hexane) gave 1-(2,3-dichlorophenyl)-2-(pyridin-3-yl)ethanone (1.07 g, 13%) as brown oil.
Reaction SMILES: [O:1]1[CH2:7][CH:6]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4[C:20]([O:27][CH3:28])=[N:21][C:22]([CH3:26])=[CH:23][C:24]=4[CH3:25])=[CH:15][C:14]=3[N+:29]([O-])=O)=[C:11]([C:32](OCC)=[O:33])[CH:10]=[N:9]2)[CH2:5][O:4][CH2:3][CH2:2]1.O.C(OCC)(=O)C>C(O)(=O)C.[Fe]>[O:1]1[CH2:7][CH:6]([N:8]2[C:12]3[C:13]4[CH:18]=[CH:17][C:16]([C:19]5[C:20]([O:27][CH3:28])=[N:21][C:22]([CH3:26])=[CH:23][C:24]=5[CH3:25])=[CH:15][C:14]=4[NH:29][C:32](=[O:33])[C:11]=3[CH:10]=[N:9]2)[CH2:5][O:4][CH2:3][CH2:2]1
Reactant: CCOC(=O)c1cnn(C2COCCOC2)c1-c1ccc(-c2c(C)cc(C)nc2OC)cc1[N+](=O)[O-]
Agent: [Fe]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: COc1nc(C)cc(C)c1-c1ccc2c(c1)[nH]c(=O)c1cnn(C3COCCOC3)c12
Temperature: 80 °C
Reaction time: 4.25 h
Yield: 11.8 %

Procedure:
Iron powder (17 mg) was added to a solution of ethyl 1-(1,4-dioxepan-6-yl)-5-{4-(2-methoxy-4,6-dimethylpyridin-3-yl)-2-nitrophenyl}-1H-pyrazole-4-carboxylate (15 mg) in acetic acid (1 mL)-water (0.05 mL), and the mixture was stirred at 80° C. for 4.25 hours in a nitrogen atmosphere. The reaction mixture was returned to room temperature, and ethyl acetate (5 mL) was added to the reaction mixture. The insoluble matter was removed by filtration through Celite™. The filtrate was concentrated under reduced pressure. A solution of the residue in ethyl acetate was sequentially washed with a saturated aqueous sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by preparative thin-layer chromatography (silica gel, ethyl acetate/n-heptane, 66%) to give the title compound (1.5 mg).
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:19](=[O:20])[C:18]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]4[C:29]([C:34]#[N:35])=[CH:30][CH:31]=[CH:32][CH:33]=4)=[CH:24][CH:23]=3)=[C:17]([CH2:36][CH2:37][CH3:38])[N:16]3[N:39]=[CH:40][N:41]=[C:15]23)[CH2:10][CH2:9]1)C1C=CC=CC=1.O1CCCC1>[C].[Pd].C(O)C>[O:20]=[C:19]1[C:18]([CH2:21][C:22]2[CH:23]=[CH:24][C:25]([C:28]3[C:29]([C:34]#[N:35])=[CH:30][CH:31]=[CH:32][CH:33]=3)=[CH:26][CH:27]=2)=[C:17]([CH2:36][CH2:37][CH3:38])[N:16]2[N:39]=[CH:40][N:41]=[C:15]2[N:14]1[CH:11]1[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n(C2CCN(Cc3ccccc3)CC2)c2ncnn12
Agent: [Pd]
Solvent: CCO
Solvent: C1CCOC1
Product: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n(C2CCNCC2)c2ncnn12
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A mixture of 4′-{[4-(1-benzylpiperidin-4-yl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (4.82 g), 10% palladium-carbon (containing water by 50%, 2.39 g), tetrahydrofuran (30 mL) and ethanol (60 mL) was stirred at room temperature for 2 days under a hydrogen atmosphere. The reaction mixture was filtered, and the solvent was evaporated. The residue was purified by basic silica gel chromatography [eluent: methanol/ethyl acetate=0/10→05/95 (volume ratio)] to give the title compound as a colorless amorphous compound (2.97 g, 74%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([NH:17]C(OCC2C3C=CC=CC=3C3C2=CC=CC=3)=O)([C:14]([OH:16])=[O:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC)(C)(C)C.C(O)(C)C.N1CCCCC1>CN(C)C=O>[NH2:17][C:10]1([C:14]([OH:16])=[O:15])[CH2:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]1
Reactant: CC(C)(C)OC(=O)N1CCCC(NC(=O)OCC2c3ccccc3-c3ccccc32)(C(=O)O)C1
Solvent: C1CCNCC1
Solvent: COC(C)(C)C
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCCC(N)(C(=O)O)C1
Temperature: 25 °C
Yield: 81 %

Procedure:
1-(tert-butoxycarbonyl)-3-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}piperidine-3-carboxylic acid was resolved by chiral HPLC resolution {Merck 50 mm 16 μm Kromasil Chirose 2 No. CT9014, tert-butylmethylether/iso-propanol (90/10). The first eluted enantiomer (800 mg, 1.71 mmol) 1-(tert-butoxycarbonyl)-3-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}piperidine-3-carboxylic acid (Isomer 1) was dissolved in N,N-dimethylformamide (10 ml) and piperidine (0.85 ml, 8.55 mmol) added. The mixture was stirred at room temperature over night. The resulting white precipitate was filtered off. The filtrates were concentrated and the residues purified by column chromatography on silica eluting with saturated ammonia in methanol/dichloromethane (25/75). The fractions containing the desired product were combined with the filtered solids and evaporated to give 3-amino-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (Isomer 1) (339 mg, 81%); 1H NMR Spectrum: (D2O) 1.44 (s, 9H); 1.63 (m, 1H); 1.79 (d, 1H); 1.97 (d, 1H); 2.10 (m, 1H); 2.88 (t, 1H); 3.33 (d, 1H); 4.09 (m, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([NH2:12])=[S:11])=[CH:5][CH:4]=1.Cl[CH2:14][CH:15]=O>CCO>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10]2[S:11][CH:14]=[CH:15][N:12]=2)=[CH:7][CH:8]=1
Reactant: O=CCCl
Reactant: COc1ccc(NC(N)=S)cc1
Solvent: CCO
Product: COc1ccc(Nc2nccs2)cc1
Temperature: 25 °C

Procedure:
A mixture of (4-methoxy-phenyl)-thiourea (3.0 g, 16.5 mmol) and a 45% aqueous solution of chloroacetaldehyde (12 mL, 82.4 mmol, 5.0 equiv) in EtOH (23 mL) is heated to reflux for 1 h. The resulting dark orange solution is allowed to cool to RT and concentrated in vacuo. NaHCO3 is then added to the oily residue until CO2 evolution subsides and a beige precipitate forms. The product is collected by vacuum filtration, washed thoroughly with water (600 mL), and dried in vacuo. Title compound: ES-MS: 207.0 [M+H]+; single peak at tR=5.32 min (System 1); Rf=0.17 (CH2Cl2/MeOH, 95/5).
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]([O:13][C:14]1[CH:19]=[C:18]([C:20]2[C:29]3[C:24](=[C:25]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[CH:26]=[CH:27][CH:28]=3)[C:23](Cl)=[N:22][N:21]=2)[CH:17]=[CH:16][N:15]=1)([CH3:12])([CH3:11])[CH3:10]>ClCCl>[CH2:1]([NH:8][C:23]1[C:24]2[C:29](=[CH:28][CH:27]=[CH:26][C:25]=2[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:20]([C:18]2[CH:17]=[CH:16][N:15]=[C:14]([O:13][C:9]([CH3:12])([CH3:11])[CH3:10])[CH:19]=2)=[N:21][N:22]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)Oc1cc(-c2nnc(Cl)c3c(-c4ccccc4)cccc23)ccn1
Reactant: NCc1ccccc1
Solvent: ClCCl
Product: CC(C)(C)Oc1cc(-c2nnc(NCc3ccccc3)c3c(-c4ccccc4)cccc23)ccn1
Temperature: 100 °C
Yield: 50.8 %

Procedure:
Benzylamine (5.00 mL, 45.8 mmol) was added to 1-(2-(tert-butoxy)pyridin-4-yl)-4-chloro-5-phenylphthalazine (0.200 g, 0.513 mmol) and heated in a sealed tube at 100° C. for 12 h. The reaction mixture was diluted with dichloromethane (100 mL) and washed with water (50 mL) followed by brine (25 mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography using Combiflash Isco (REDISEP®, basic Al2O3, 80 g, 0-70% ethyl acetate/petroleum ether) to remove excess benzyl amine. The resulting residue was then purified by preparative HPLC (Condition 33 as described in general methods) to afford N-benzyl-4-(2-(tert-butoxy)pyridin-4-yl)-8-phenylphthalazin-1-amine (0.120 g, 50.8%) as a white solid. LCMS (Condition 34): retention time 2.67 min, [M+1]=461.2. HPLC (Condition 35): retention time=21.80 min, purity 99.30%. 1H NMR (400 MHz, DMSO-d6) δ 1.63 (s, 9 H), 4.50 (d, J=5.2 Hz, 2 H), 5.07 (t, J=5.2 Hz, 1 H), 6.90 (dd, J=0.4 Hz, J=0.8 Hz, 1 H), 7.00-7.03 (m, 2 H), 7.17 (dd, J=1.6 Hz, J=5.2 Hz, 1 H), 7.22-7.28 (m, 3 H), 7.42-7.50 (m, 5 H), 7.67 (dd, J=1.2 Hz, J=6.8 Hz, 1 H), 7.85-7.93 (m, 2 H), 8.31 (dd, J=0.4 Hz, J=5.2 Hz, 1 H).
Reaction SMILES: P(=O)(O)(O)O.[C:6]1([NH:12][C:13]2[CH:21]=[C:20]([C:22](O)=[O:23])[C:19]([NH:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[CH:18][C:14]=2[C:15](O)=[O:16])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>O>[CH:29]1[CH:30]=[C:31]2[C:22]([C:20]3[C:19]([NH:25][C:26]2=[CH:27][CH:28]=1)=[CH:18][C:14]1[C:15]([C:11]2[C:6]([NH:12][C:13]=1[CH:21]=3)=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:16])=[O:23]
Reactant: O=C(O)c1cc(Nc2ccccc2)c(C(=O)O)cc1Nc1ccccc1
Agent: O=P(O)(O)O
Solvent: O
Product: O=c1c2ccccc2[nH]c2cc3c(=O)c4ccccc4[nH]c3cc12
Temperature: 50 °C
Reaction time: 1 h
Yield: 15.3 %

Procedure:
One hundred and thirty-five ml of polyphosphoric acid and 65 ml of 85% phosphoric acid are mixed in a mechanically stirred beaker and cooled to 50° C. Four grams of 2,5-di(phenylamino)terephthalic acid (DAA) are slowly added in small portions and under agitation by Gifford-Wood homogenizer. Each portion is dissolved before adding another one, checked by dipping a glass rod into the viscous reaction mixture and examining for solid particles clinging to the rod. During this time, the temperature of the reaction mixture is kept at 55° C. or below by cooling with an external water bath. After having dissolved all of the DAA, the solution is heated to 100° C. under stirring and kept at that temperature for 1 hour. The reaction mixture is cooled and poured into 2 l of water under mechanical stirring. The slurry which forms is stirred for 10 minutes and filtered. The filter cake is washed acid-free with water and the water-wet solid reslurried in 600 ml of water. The pH of the slurry is adjusted to 12 with concentrated 50% by weight aqueous NaOH solution under stirring. The slurry is heated to 60° C., held at that temperature for 10 minutes with continued stirring and filtered immediately. The filter cake is washed with water and dried in a vacuum oven at 70°-80° C. to give 0.55 g (15% yield) of quinacridone by-product. Combined filtrate and wash water are stirred and acidified with acetic acid to a pH of 4. The formed precipitate is stirred for 10 minutes, filtered and washed acid-free with water. Vacuum oven drying overnight at 70°-80° C., under slight N2 purge, gives 2.8 g (74% yield) of orange microcrystalline 2-(phenyl)amino-3-carboxy-9(10H) acridinone.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.O.Cl.[CH2:12]([N:19]1[CH2:24][CH2:23][CH2:22][C:21](=O)[CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[OH-].[K+].C(O)(C)C>>[CH2:12]([N:19]1[CH2:24][CH2:23][CH:22]=[C:21]([C:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[NH:1][CH:2]=2)[CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: c1ccc2[nH]ccc2c1
Reactant: O=C1CCCN(Cc2ccccc2)C1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)O
Product: C1=C(c2c[nH]c3ccccc23)CN(Cc2ccccc2)CC1
Temperature: 80 °C

Procedure:
A mixture of indole (2 g, 17 mmol) and 1-benzyl-piperidin-3-one hydrochloride hydrate (7.7 g, 34 mmol) and 2N KOH/isopropanol is heated at 80° C. for 14 hours, cooled to room temperature, poured over ice/water and extracted with ethyl acetate. The extracts are combined, washed with water, dried over Na2SO4 and concentrated in vacuo to afford the title product, identified by HPLC and mass spectral analyses.
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[CH2:18][C:6]2=[C:7]([C:13]3[CH:17]=[CH:16][NH:15][N:14]=3)[S:8][C:9](S(C)=O)=[C:5]2[C:4](=[O:19])[CH2:3]1.[H-].[Na+].[CH:23]1([OH:27])[CH2:26][CH2:25][CH2:24]1>C1COCC1>[CH:23]1([O:27][C:9]2[S:8][C:7]([C:13]3[CH:17]=[CH:16][NH:15][N:14]=3)=[C:6]3[CH2:18][C:2]([CH3:20])([CH3:1])[CH2:3][C:4](=[O:19])[C:5]=23)[CH2:26][CH2:25][CH2:24]1
Reactant: OC1CCC1
Reactant: CS(=O)c1sc(-c2cc[nH]n2)c2c1C(=O)CC(C)(C)C2
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC1(C)CC(=O)c2c(OC3CCC3)sc(-c3cc[nH]n3)c2C1
Yield: 12 %

Procedure:
To a solution of 6,6-dimethyl-3-methanesulphinyl-1-(pyrazol-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one (178 mg, 0.59 mmol) in cyclobutanol (1 mL) and THF (3 mL) was added sodium hydride (70 mg of a 60% dispersion in oil, 1.76 mmol). After effervescence had ceased the mixture was heated at 95° C. for 2h before the solvent was evaporated. The residue was partitioned between EtOAc (20 mL) and water (20 mL) and the organic layer separated, dried (Na2SO4) and evaporated. The residue was chromatographed on silica gel, eluting with petrol:EtOAc (1:1) to give the title compound (22 mg, 12%) as a pale yellow solid. mp 202-204° C. Found: C, 62.48; H, 6.24; N, 8.49%. C17H20N2O2S .0.5(H2O) requires: C, 62.74; H, 6.50; N, 8.61% 1H NMR (360 MHz, CDCl3) δ 1.06 (6H, s), 1.60-1.76 (1H, m), 1.86-1.97 (1H, m), 2.37 (2H, s), 2.38-2.47 (2H, m), 2.50-2.60 (2H, m), 2.79 (2H, s), 4.76 (1H, pentet, J=7.2 Hz), 6.45 (1H, d, J=2.4 Hz), 7.62 (1H, d, J=2.4 Hz). MS (ES+) 317 (M+1).
Reaction SMILES: S(C1C=CC(C)=CC=1)(O[CH:5]([CH2:7][CH2:8][O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH3:6])(=O)=O.[NH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.C(OCC)C.C(Cl)(Cl)Cl>CO>[CH3:6][CH:5]([N:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1)[CH2:7][CH2:8][O:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: C1CCNCC1
Reactant: Cc1ccc(S(=O)(=O)OC(C)CCOc2ccccc2)cc1
Solvent: ClC(Cl)Cl
Solvent: CO
Solvent: CCOCC
Product: CC(CCOc1ccccc1)N1CCCCC1
Yield: 75 %

Procedure:
In a sealed tube, 10 g of the 4-phenoxy-2-butyl tosylate was reacted with 11.2 g of piperidine in 60 ml of absolute methyl alcohol for one hour at 125° C. After the reaction solution was condensed under reduced pressure. 100 ml of diethyl ether was added into the solution and the solution was separated with 20% aqueous sodium hydroxide solution. After the ether layer was dried with anhydrous sodium sulfate, ether was removed under reduced pressure therefrom. The residue thus obtained was subjected to an alumina-column chromatography using chloroform as the solvent to give 5.46 g of 1-(1-methyl-3-phenoxypropyl)piperidine in a yield of 75%.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH2:9][C@@H:10]([C:19]([OH:21])=O)[NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].P(C#N)(=O)(OCC)OCC.C(N(CC)CC)C.O>CN(C)C=O>[C:15]([O:14][C:12]([NH:11][C@@H:10]1[C:19](=[O:21])[NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[O:8][CH2:9]1)=[O:13])([CH3:18])([CH3:17])[CH3:16]
Reactant: CC(C)(C)OC(=O)N[C@@H](COc1ccccc1N)C(=O)O
Agent: CCOP(=O)(C#N)OCC
Solvent: CN(C)C=O
Solvent: O
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N[C@H]1COc2ccccc2NC1=O
Yield: 61.2 %

Procedure:
In 120 ml of N,N-dimethylformamide is dissolved 21.4 g of O-(o-aminophenyl)-Boc-L-serine obtained in Example 2, and 14 g of diethyl phosphorocyanidate is added dropwise to the solution with stirring at ice bath temperature. The mixture is stirred for 10 minutes, and 7 g of triethylamine is added dropwise to the mixture. After stirring for 1 hour, the mixture is poured in ice-cooled water. The deposited material is collected by filtration, washed with water, dried and recrystallized from ethyl acetate-hexane to give 12.3 g of 3(S)-tert-butoxycarbonylamino-2,3,4,5-tetrahydro-1,5-benzoxazepine-4-one as colorless plates, melting at 202°-203° C.