Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH3:19])[C:12]([N+:16]([O-])=O)=[C:13]([CH3:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(O)(=O)C.[Zn]>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([CH3:15])[C:12]([NH2:16])=[C:11]([CH3:19])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1cc(OCc2ccccc2)cc(C)c1[N+](=O)[O-]
Agent: [Zn]
Solvent: CC(=O)O
Product: Cc1cc(OCc2ccccc2)cc(C)c1N
Yield: 90.5 %

Procedure:
Zinc dust is added to a solution of 5-benzyloxy-2-nitro-m-xylene (22.9 g) in 250 ml of glacial acetic acid. The reaction mixture is stirred until the solution is colorless. The reaction mixture is cooled, filtered through celite to remove excess zinc and the filtrate diluted with H2O and cooled with ice. NH3 is added to make the solution slightly alkaline followed by a small amount of sodium hydrosulfite. The product is filtered, dissolved in methylene chloride, dried and concentrated to give 18.3 grams of a tan solid.
Reaction SMILES: [F:1][C:2]1[C:3]([CH:12]([CH3:14])[CH3:13])=[C:4]([C:10]#[N:11])[C:5](=[O:9])[NH:6][C:7]=1[CH3:8]>CO.[Ni]>[NH2:11][CH2:10][C:4]1[C:5](=[O:9])[NH:6][C:7]([CH3:8])=[C:2]([F:1])[C:3]=1[CH:12]([CH3:14])[CH3:13]
Reactant: Cc1[nH]c(=O)c(C#N)c(C(C)C)c1F
Agent: [Ni]
Solvent: CO
Product: Cc1[nH]c(=O)c(CN)c(C(C)C)c1F
Yield: 88.2 %

Procedure:
5-Fluoro-4-isopropyl-6-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (100 mg, 0.515 mmol) in 100 mL flask was dissolved in a mixture of MeOH (6 mL) and 2 mL NH3aq (2 mL, 25%). Reduction was conducted using H-Cube with Raney-Ni as a catalyst at room temperature for 3-4 h. On completion of reaction (monitored by TLC), reaction was concentrated under reduced pressure to afford titled compound as a grey solid (90 mg, 90%). 1H NMR (400 MHz, CD3OD) δ ppm 4.04 (s, 2H), 3.22 (m, 1H), 2.24 (d, J=3.4 Hz, 3H), 1.32 (dd, J=7.0, 1.8 Hz, 6H); LCMS E-S (M+H)=199.2.
Reaction SMILES: [CH3:1][N:2]([CH:4]=[C:5]1[C:17]2[N:16]3[CH:18]=[CH:19][N:20]=[C:15]3[C:14](=[O:21])[NH:13][C:12]=2[C:11]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]1=2)[CH3:3].C(OC(N(C)C)N(C)C)(C)(C)C.C1N2C3CC4C=CC=CC=4C=3NC(=O)C2=NC=1.O>CN(C)C=O.CO>[CH3:3][N:2](/[CH:4]=[C:5]1\[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=2[C:12]2[NH:13][C:14](=[O:21])[C:15]3[N:16]([CH:18]=[CH:19][N:20]=3)[C:17]\1=2)[CH3:1]
Reactant: CN(C)C=c1c2ccccc2c2[nH]c(=O)c3nccn3c12
Agent: CN(C)C(OC(C)(C)C)N(C)C
Agent: O=c1[nH]c2c(n3ccnc13)Cc1ccccc1-2
Solvent: CN(C)C=O
Solvent: O
Solvent: CO
Product: CN(C)/C=c1\c2ccccc2c2[nH]c(=O)c3nccn3c12
Reaction time: 0.5 h

Procedure:
10-Dimethylaminomethylene-5H,10H-imidazo-[1,2-a]indeno[1,2-e]pyrazin-4-one may be prepared in the following way: 6.3 g of t-butoxybis(dimethylamino)-methane are added dropwise over 5 minutes, at a temperature in the region of 25° C., to a suspension of 5.5 g of 5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one in 100 ml of dimethylformamide. After stirring for 30 minutes at the same temperature, the mixture is poured into 500 ml of distilled water and extracted 5 times with 1.5 liters in total of chloroform. The organic extracts are combined, washed with 250 ml of distilled water, dried over anhydrous magnesium sulphate and concentrated to dryness under reduced pressure (15 mmHg; 2 kPa) at 60° C. The product obtained (4.5 g) is suspended in 25 ml of methanol, filtered off, washed twice with 20 ml in total of methanol and dried under reduced pressure (15 mmHg; 2 kPa) at 20° C. The product obtained (4.5 g) is dissolved in 45 ml of boiling dimethyl2formamide and, after cooling, the solution is stored for 4 hours at a temperature in the region of 5° C. The crystals are isolated by filtration, washed successively with 10 ml of dimethylformamide and 10 ml of acetone, and dried to dryness under reduced pressure (1 mmHg; 0.13 kPa) at 100° C. 4 g of 10-(E-dimethylaminomethylene-5H,10H-imidazo[1,2-a)indeno-[1,2-e]pyrazin-4-one are thus obtained, melting at 293° C. [NMR spectrum: (200 MHz; DMSO-d6 ; δ in ppm): 3.35 [S 6H: --N(CH3)2 1; 7.18 and 7.28 (2t, J=7.5 Hz, 2H: --H7 and --H8); 7.48 and 7.92 (2d, J=7.5 Hz, 1H each: --H6 and --H9); 7.63 and 8.50 (2 broad s, 1H each: --H of the imidazole); 8.09 (s, 1H: =CH--N); 12.30 (mult., 1H: --NH--)].
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]([O:14][CH3:15])=[O:13])[C:6](=[O:16])[C:5]12[O:21][CH2:20][C:19]([CH3:23])([CH3:22])[CH2:18][O:17]1.[CH3:24][S:25](Cl)(=[O:27])=[O:26]>N1C=CC=CC=1>[CH3:22][C:19]1([CH3:23])[CH2:20][O:21][C:5]2([C:4]3[C:8](=[CH:9][CH:10]=[C:2]([NH:1][S:25]([CH3:24])(=[O:27])=[O:26])[CH:3]=3)[N:7]([CH2:11][C:12]([O:14][CH3:15])=[O:13])[C:6]2=[O:16])[O:17][CH2:18]1
Reactant: COC(=O)CN1C(=O)C2(OCC(C)(C)CO2)c2cc(N)ccc21
Reactant: CS(=O)(=O)Cl
Solvent: c1ccncc1
Product: COC(=O)CN1C(=O)C2(OCC(C)(C)CO2)c2cc(NS(C)(=O)=O)ccc21
Temperature: 25 °C
Reaction time: 0.42 h
Yield: 92 %

Procedure:
A solution of methyl 2-(5′-amino-5,5-dimethyl-2′-oxospiro[[1,3]dioxane-2,3′-indoline]-1′-yl)acetate (307 mg, 0.958 mmol) in pyridine (15 ml) was cooled to 0° C. and methanesulfonyl chloride (0.090 ml, 1.150 mmol) was added; the reaction was warmed to room temperature and stirred for 25 minutes. The solvent was evaporated, and the residue was partitioned between ethyl acetate and 1N HCl; the organic phase was dried over Na2SO4, filtered and evaporated. The crude was purified by flash chromatography on silica gel (DCM:MeOH from 99.5:0.5 to 98.75:1.25) affording methyl 2-(5,5-dimethyl-5′-(methylsulfonamido)-2′-oxospiro[[1,3]dioxane-2,3′-indoline]-1′-yl)acetate (351 mg, 0.881 mmol, 92% yield). MS/ESI+ 398.9 [MH]+.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([OH:12])=O)=[N:2]1.Cl.[CH3:14][NH:15][O:16][CH3:17].CN(C)CCCN=C=NCC.N1C=CC=CC=1>O1CCCC1>[CH3:17][O:16][N:15]([CH3:14])[C:10]([C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][N:2]=1)=[O:12]
Reactant: O=C(O)c1n[nH]c2ccccc12
Reactant: CNOC
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: CON(C)C(=O)c1n[nH]c2ccccc12
Temperature: 25 °C
Reaction time: 20 h
Yield: 69.1 %

Procedure:
In a round-bottomed flask, 4.0 g of 1H-indazole-3-carboxylic acid, 2.6 g of N,O-dimethylhydroxylamine hydrochloride, 9.4 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 8.4 ml of pyridine are placed in 120 ml of tetrahydrofuran. The mixture is stirred at ambient temperature for 20 h. The mixture is concentrated and the residue is taken up in water. The yellow precipitate obtained is washed with water and then dried under reduced pressure. 3.5 g of compound are obtained.
Reaction SMILES: [Na].[F:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:17]3[N:16]=[C:15]4[CH2:18][CH2:19][CH2:20][C:21](=O)[CH:22]([CH2:23][C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=5)[C:14]4=[CH:13][C:12]=3[CH:11]=[N:10]2)=[CH:5][CH:4]=1.[CH3:31][C:32](=[O:35])[CH:33]=[CH2:34]>CCO>[F:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:17]3[N:16]=[C:15]4[CH2:18][CH2:19][CH2:20][C:21]5[C:22]([CH2:23][C:24]6[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=6)([CH2:34][CH2:33][C:32](=[O:35])[CH:31]=5)[C:14]4=[CH:13][C:12]=3[CH:11]=[N:10]2)=[CH:7][CH:8]=1
Reactant: C=CC(C)=O
Reactant: O=C1CCCc2nc3c(cnn3-c3ccc(F)cc3)cc2C1Cc1ccccn1
Agent: [Na]
Solvent: CCO
Product: O=C1C=C2CCCc3nc4c(cnn4-c4ccc(F)cc4)cc3C2(Cc2ccccn2)CC1
Temperature: 60 °C
Reaction time: 1.5 h
Yield: 49.7 %

Procedure:
Sodium (1.09 g, 47.4 mmol) and EtOH (355 mL) were stirred together until a solution was formed then 1-(4-fluorophenyl)-5-(pyridin-2-ylmethyl)-5,7,8,9-tetrahydrocyclohepta[b]pyrazolo[4,3-e]pyridin-6(1H)-one (115, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (16.47 g, 42.6 mmol) was added. The mixture was heated to about 60° C. then but-3-en-2-one (4.14 mL, 50.2 mmol) was added over about 50 min. The mixture was stirred at about 60° C. for about 90 min then it was cooled and concentrated under reduced pressure. The material was partitioned between EtOAc (250 mL) and water (150 mL) then the aqueous layer was extracted with EtOAc (100 mL). The combined organics were washed with brine (30 mL) then dried over MgSO4, filtered and concentrated under reduced pressure. The material was purified on silica gel (330 g) using a gradient from 0-100% EtOAc in DCM. Product fractions were combined and concentrated under reduced pressure to yield rac-9-(4-fluorophenyl)-12b-(pyridin-2-ylmethyl)-1,5,6,7,9,12b-hexahydrobenzo[3,4]cyclohepta[1,2-b]pyrazolo[4,3-e]pyridin-3(2H)-one (116, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (9.28 g, 50%); LC/MS, method 3, Rt=1.61, 2.40 min, MS m/z 439 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.83 (s, 1H), 8.43 (s, 1H), 8.36-8.28 (m, 3H), 7.61-7.57 (m, 1H), 7.44-7.36 (m, 2H), 7.18-7.11 (m, 2H), 5.97 (s, 1H), 3.88 (d, J=13.4 Hz, 1H), 3.67 (d, J=13.5 Hz, 1H), 3.27-3.15 (m, 1H), 2.98-2.93 (m, 1H), 2.87-2.74 (m, 1H), 2.48-2.40 (m, 1H), 2.39-2.27 (m, 1H), 2.23-2.09 (m, 2H), 1.94-1.75 (m, 2H), 1.56-1.49 (m, 1H).
Reaction SMILES: CS(O[CH2:6][CH2:7][N:8]1[C:20]2[C:19]3[CH2:18][CH2:17][CH2:16][CH2:15][C:14]=3[N:13]=[C:12]([N:21]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:11]=2[N:10]=[C:9]1[CH2:36][CH2:37][CH2:38][CH3:39])(=O)=O.[C:40]1([SH:46])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C(N(CC)CC)C>CN(C)C=O>[CH2:36]([C:9]1[N:8]([CH2:7][CH2:6][S:46][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:20]2[C:19]3[CH2:18][CH2:17][CH2:16][CH2:15][C:14]=3[N:13]=[C:12]([N:21]([C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])[C:29]([O:31][C:32]([CH3:35])([CH3:33])[CH3:34])=[O:30])[C:11]=2[N:10]=1)[CH2:37][CH2:38][CH3:39]
Reactant: CCCCc1nc2c(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)nc3c(c2n1CCOS(C)(=O)=O)CCCC3
Reactant: Sc1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CCCCc1nc2c(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)nc3c(c2n1CCSc1ccccc1)CCCC3
Temperature: 80 °C
Yield: 86.1 %

Procedure:
A round bottom flask was charged with a magnetic stir bar, 2-{4-[bis(tert-butoxycarbonyl)amino]-2-butyl-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-1-yl }ethyl methanesulfonate (0.61 g, 1.08 mmol), benzenethiol (0.21 g, 1.88 mmol), triethylamine (0.25 g, 2.43 mmol) and anhydrous dimethyl formamide (11 mL) under a nitrogen atmosphere. The reaction mixture was heated to 80° C. to give a dark yellow, homogeneous solution that was maintained at 80° C. for 2.5 hours at which time the reaction was judged to be complete. The solution was cooled and then partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The layers were separated. The organic layer was washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous sodium sulfate, filtered and then concentrated under reduced pressure to afford a yellow oil. The material was purified by chromatography over silica gel (95/5 dichloromethane/methanol) to provide di(tert-butyl) 2-butyl-1-[2-(phenylthio)ethyl]-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-4-ylimidodicarbonate (0.54 g, 0.93 mmol) as a light yellow oil. MS (CI) for C32H44N4O4S m/z 581 (MH+), 481, 381, 245.
Reaction SMILES: ClC1C=C(Cl)N=C(C2C=CC=CC=2)N=1.Cl[C:16]1[CH:21]=[C:20]([Cl:22])[N:19]=[C:18]([S:23][C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=2)[N:17]=1.[CH2:31]([CH:33]([CH2:36][CH2:37][CH2:38][CH3:39])[CH2:34][OH:35])[CH3:32]>CC(C)CCO>[Cl:22][C:20]1[CH:21]=[C:16]([O:35][CH2:34][CH:33]([CH2:31][CH3:32])[CH2:36][CH2:37][CH2:38][CH3:39])[N:17]=[C:18]([S:23][C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=2)[N:19]=1
Reactant: CCCCC(CC)CO
Reactant: Cc1ccc(Sc2nc(Cl)cc(Cl)n2)cc1
Agent: Clc1cc(Cl)nc(-c2ccccc2)n1
Solvent: CC(C)CCO
Product: CCCCC(CC)COc1cc(Cl)nc(Sc2ccc(C)cc2)n1
Yield: 85 %

Procedure:
The preparation is carried out analogously to the method described in Example 3, with 4,6-dichloro-2-phenylpyrimidine being replaced by 4,6-dichloro-2-(p-methylphenylthio)pyrimidine and 3-methylbutanol by 2-ethylhexanol. The title compound is obtained as a resin in a yield of 85% of theory.
Reaction SMILES: Cl.[C:2]1([CH:8]2[N:12]3[C:13](=[O:17])[CH2:14][NH:15][CH2:16][CH:11]3[CH2:10][CH2:9]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[CH:27]([N:30]=[C:31]=[O:32])([CH3:29])[CH3:28]>ClCCl>[CH:27]([NH:30][C:31]([N:15]1[CH2:14][C:13](=[O:17])[N:12]2[C@@H:8]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:9][CH2:10][C@H:11]2[CH2:16]1)=[O:32])([CH3:29])[CH3:28]
Reactant: CC(C)N=C=O
Reactant: O=C1CNCC2CCC(c3ccccc3)N12
Agent: Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)NC(=O)N1CC(=O)N2[C@@H](CC[C@@H]2c2ccccc2)C1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of the HCl salt of racemic-(6R,8aS)-6-phenylhexahydropyrrolo[1,2-a]pyrazin-4(1H)-one (0.25 g, 0.99 mmol) and DIEA (0.345 mL, 1.99 mmol) in dichloromethane (4 mL) at ambient temperature was added isopropyl isocyanate (0.146 mL, 1.48 mmol). The mixture was stirred at ambient temperature for 18 h. The solvent was removed under vacuum and the residue was partitioned between ethyl acetate and brine. The EtOAc layer was separated, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to HPLC purification on C-18 stationary phase eluted with water/acetonitrile/TFA mobile phase. Concentration of appropriate fractions afforded (6R,8aS)-N-isopropyl-4-oxo-6-phenylhexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxamide. HPLC RT=2.68 min (Method A); ES MS (M+H)=302.3.
Reaction SMILES: [CH3:1][C:2]([OH:25])([CH3:24])[CH2:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[NH:13][C:14]3[C:19]([CH:20]=2)=[CH:18][C:17]([N+:21]([O-])=O)=[CH:16][CH:15]=3)=[O:11])[CH2:6][CH2:5]1>CO.[C].[Pd]>[NH2:21][C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12]([C:10]([N:7]1[CH2:8][CH2:9][CH:4]([CH2:3][C:2]([CH3:24])([OH:25])[CH3:1])[CH2:5][CH2:6]1)=[O:11])=[CH:20]2
Reactant: CC(C)(O)CC1CCN(C(=O)c2cc3cc([N+](=O)[O-])ccc3[nH]2)CC1
Agent: [Pd]
Solvent: CO
Product: CC(C)(O)CC1CCN(C(=O)c2cc3cc(N)ccc3[nH]2)CC1
Temperature: 25 °C
Reaction time: 24 h
Yield: 75.3 %

Procedure:
To a solution of 838 mg of 2-methyl-1-{1-[(5-nitro-1H-indol-2-yl)carbonyl]piperidin-4-yl}propan-2-ol in 15 mL of methanol was added 80 mg of 10% palladium-carbon, followed by stirring under a hydrogen atmosphere at room temperature for 1 day. Insoluble material was removed by filtration through Celite, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography [chloroform:methanol=1:0-10:1], and then solidified from hexane-ethyl acetate to obtain 576 mg of 1-{1-[(5-amino-1H-indol-2-yl)carbonyl]piperidin-4-yl}-2-methylpropan-2-ol as a pale brown solid.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([S:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=1)[C:9]([CH2:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[CH:8]2)=[O:4].[OH-].[Na+]>O1CCOCC1>[O:27]([CH2:26][C:9]1[N:10]([CH2:14][C:15]2[CH:16]=[CH:17][C:18]([S:21][C:22]([F:25])([F:24])[F:23])=[CH:19][CH:20]=2)[C:11]2[C:7]([CH:8]=1)=[CH:6][C:5]([C:3]([OH:4])=[O:2])=[CH:13][CH:12]=2)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: COC(=O)c1ccc2c(c1)cc(COc1ccccc1)n2Cc1ccc(SC(F)(F)F)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: O=C(O)c1ccc2c(c1)cc(COc1ccccc1)n2Cc1ccc(SC(F)(F)F)cc1

Procedure:
2-Phenoxymethyl-1-(4-trifluoromethylsulfanyl-benzyl)-1H-indole-5-carboxylic acid methyl ester was dissolved in dioxane and treated with 1M NaOH at 50° C. for 16 h. The solvents were evaporated and the remaining solid treated with 0.5 ml HCl/1 ml ethylacetate and extracted with water.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:9]([N:12]([CH3:14])[CH3:13])(=[O:11])=[O:10])[CH:5]=[CH:6][C:7]=1F.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][C:23]([OH:25])=[O:24])=[CH:18][C:17]=1[OH:26]>>[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][C:23]([OH:25])=[O:24])=[CH:18][C:17]=1[O:26][C:7]1[CH:6]=[CH:5][C:4]([S:9]([N:12]([CH3:14])[CH3:13])(=[O:11])=[O:10])=[CH:3][C:2]=1[Cl:1]
Reactant: O=C(O)Cc1ccc(Cl)c(O)c1
Reactant: CN(C)S(=O)(=O)c1ccc(F)c(Cl)c1
Product: CN(C)S(=O)(=O)c1ccc(Oc2cc(CC(=O)O)ccc2Cl)c(Cl)c1

Procedure:
The title compound was prepared by the method of example 2 step (iii) using 3-chloro-4-fluoro-N,N-dimethylbenzenesulfonamide and the product of example 1 step (iii).
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:25]=[CH:24][C:8]([O:9][C:10]2[S:11][C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH:21]([NH2:23])[CH3:22])=[CH:17][CH:16]=3)=[CH:13][N:14]=2)=[CH:7][CH:6]=1)([CH3:3])[CH3:2].C(N(CC)CC)C.[C:33](OC(=O)C)(=[O:35])[CH3:34]>C(Cl)Cl>[CH:1]([O:4][C:5]1[CH:25]=[CH:24][C:8]([O:9][C:10]2[S:11][C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH:21]([NH:23][C:33](=[O:35])[CH3:34])[CH3:22])=[CH:17][CH:16]=3)=[CH:13][N:14]=2)=[CH:7][CH:6]=1)([CH3:2])[CH3:3]
Reactant: CC(C)Oc1ccc(Oc2ncc(-c3ccc(C(C)N)cc3)s2)cc1
Reactant: CC(=O)OC(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)NC(C)c1ccc(-c2cnc(Oc3ccc(OC(C)C)cc3)s2)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 76 %

Procedure:
To a solution of Example 1F (0.15 g, 0.0004 mol) and excess triethylamine (2 mL) in methylene chloride (5 mL) was added excess acetic anhydride (1 mL) and the mixture was stirred at room temperature for 15 minutes. After quenching with methanol (5 mL), the solvent was concentrated and the residue was purified on silica gel (50˜75% ethyl acetate in hexane) to give 0.12 g of the title compound (76% yield). 1H NMR (300 MHz, CDCl3) δ ppm 1.35 (d, J=6.25 Hz, 6 H) 1.49 (d, J=6.99 Hz, 3 H) 2.00 (s, 3 H) 4.44-4.60 (m, 1 H) 5.06-5.20 (m, 1 H) 5.67 (d, J=6.99 Hz, 1 H) 6.87-6.97 (m, 2 H) 7.16-7.24 (m, 2 H) 7.27-7.34 (m, 2 H) 7.37 (s, 1 H) 7.38-7.44 (m, 2 H). MS (ESI), m/z 396.9 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:12]=[C:11]([N+:13]([O-:15])=[O:14])[CH:10]=[C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]=1O.P(Cl)(Cl)([Cl:19])=O>CN(C=O)C>[Cl:19][C:3]1[C:2]([Br:1])=[CH:12][C:11]([N+:13]([O-:15])=[O:14])=[CH:10][C:4]=1[C:5]([O:7][CH2:8][CH3:9])=[O:6]
Reactant: CCOC(=O)c1cc([N+](=O)[O-])cc(Br)c1O
Reactant: O=P(Cl)(Cl)Cl
Solvent: CN(C)C=O
Product: CCOC(=O)c1cc([N+](=O)[O-])cc(Br)c1Cl
Temperature: 90 °C
Yield: 88.9 %

Procedure:
2.38 kg (8.2 mol) of ethyl 3-bromo-5-nitrosalicylate was dissolved in 3000 ml of DMF, followed by the dropwise addition of 1.26 kg of phosphorus oxychloride at room temperature. The obtained mixture was heated to 90° C. and then maintained at that temperature under heating for 10 hours. The obtained mixture was cooled and then concentrated under reduced pressure. The obtained residue was dissolved in ethyl acetate and the obtained solution was washed with water, dehydrated and concentrated under reduced pressure to give 2.25 kg of the title compound as a colorless oil.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:9])=[C:6]([OH:8])[CH:7]=1.C(=O)([O-])O.[Na+].O.[C:16](Cl)(=[O:25])[O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>O1CCCC1.C(OCC)(=O)C>[OH:8][C:6]1[CH:7]=[C:2]([NH:1][C:16](=[O:25])[O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:3]=[CH:4][C:5]=1[CH3:9]
Reactant: Cc1ccc(N)cc1O
Reactant: O=C(Cl)OCc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: Cc1ccc(NC(=O)OCc2ccccc2)cc1O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a suspension of 5-amino-2-methylphenol (39.6 g, 321 mmol) and sodium hydrogen carbonate (40.5 g, 482 mmol) in tetrahydrofuran (300 mL)/water (150 mL) was added dropwise benzyl chlorocarbonate (48.1 mL, 321 mmol) at 0° C. over 30 min, and the mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate (300 mL) and washed with water (100 mL), and the obtained aqueous layer was extracted with ethyl acetate (2×100 ml). The combined organic layer was washed with saturated brine (100 mL), and purified by silica gel (ethyl acetate). The obtained solution was concentrated under reduced pressure to give the title compound (83.1 g, quantitatively) as a pale-brown solid. The obtained compound was used for the next reaction without purification.
Reaction SMILES: [N+:1]([C:4]1[C:9]2[N:10]3[CH2:15][CH2:14][N:13]=[C:11]3[S:12][C:8]=2[CH:7]=[CH:6][CH:5]=1)([O-])=O.N.[H][H]>[Pt].CO>[N:13]1[CH2:14][CH2:15][N:10]2[C:9]3=[C:4]([NH2:1])[CH:5]=[CH:6][CH:7]=[C:8]3[S:12][C:11]=12
Reactant: O=[N+]([O-])c1cccc2c1N1CCN=C1S2
Reactant: [H][H]
Agent: [Pt]
Agent: N
Solvent: CO
Product: Nc1cccc2c1N1CCN=C1S2

Procedure:
A mixture of 5.5 parts of 2,3-dihydro-5-nitroimidazo-[2,1-b]benzothiazole and 160 parts of methanol, saturated with ammonia is hydrogenated at normal pressure and at room temperature with 2 parts of platinum-on-charcoal catalyst 5%. After the calculated amount of hydrogen is taken up, the catalyst is filtered off and the filtrate is evaporated. The residue is crystallized from 1-butanol. The product is filtered off and dried, yielding 3 parts of 2,3-dihydroimidazo[2,1-b]benzothiazol-5-amine; mp. 229.2° C.
Reaction SMILES: O.O=C[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O.[CH:14]1[CH:19]=[C:18]2[C:20]([C:22]3[C:27]([C:28](=[O:29])[C:17]2=[CH:16][CH:15]=1)=[C:26]([NH2:30])[C:25]([S:31]([O-:34])(=[O:33])=[O:32])=[CH:24][C:23]=3Br)=[O:21].[Na+:36].[C:37]1([CH3:47])[CH:42]=[CH:41][C:40]([S:43]([NH2:46])(=[O:45])=[O:44])=[CH:39][CH:38]=1.C(=O)([O-])[O-].[Na+].[Na+].C(=O)(O)[O-].[Na+]>O.O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Na+:36].[NH2:30][C:26]1[C:27]2[C:28](=[O:29])[C:17]3[C:18](=[CH:19][CH:14]=[CH:15][CH:16]=3)[C:20](=[O:21])[C:22]=2[C:23]([NH:46][S:43]([C:40]2[CH:39]=[CH:38][C:37](=[CH2:47])[CH2:42][CH:41]=2)(=[O:44])=[O:45])=[CH:24][C:25]=1[S:31]([O-:34])(=[O:32])=[O:33]
Reactant: Cc1ccc(S(N)(=O)=O)cc1
Reactant: Nc1c(S(=O)(=O)[O-])cc(Br)c2c1C(=O)c1ccccc1C2=O
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])O
Solvent: O
Product: C=C1C=CC(S(=O)(=O)Nc2cc(S(=O)(=O)[O-])c(N)c3c2C(=O)c2ccccc2C3=O)=CC1
Temperature: 70 °C
Reaction time: 5 h
Yield: 97 %

Procedure:
Copper (II) acetate monohydrate (0.13 g, 0.00064 mol) and glucose monohydrate (1.6 g, 0.008 mol) are added to a mixture of bromaminic acid sodium salt (38.2 g, 0.1 mol) and p-toluenesulphonamide (18.8 g 0.11 mol) in water (250 mol) containing sodium carbonate (3.8 g) and sodium bicarbonate (19.0 g). The mixture which has a pH of 8.5-9.0, is heated to 70° C. and stirred at this temperature for five hours. The resulting mixture is diluted to a volume of 750 ml with water and cooled to 40° C. The solid product is filtered off and washed with a solution of sodium chloride (12 g) in water (1300 ml) to give a 97% yield 1-amino-4-(4'-methlylphenylsulphonamido)-anthraquinone-2-sulphonic acid sodium salt, a product of formula I where M denotes sodium and R denotes a group of formula IV.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[CH2:6][CH2:7][CH2:8][CH2:9][C:2]1=2.[Br:10]N1C(=O)CCC1=O>C(Cl)(Cl)Cl>[Br:10][C:5]1[S:1][C:2]2[CH2:9][CH2:8][CH2:7][CH2:6][C:3]=2[CH:4]=1
Reactant: c1cc2c(s1)CCCC2
Reactant: O=C1CCC(=O)N1Br
Solvent: ClC(Cl)Cl
Product: Brc1cc2c(s1)CCCC2
Temperature: 0 °C
Reaction time: 1 h
Yield: 90.1 %

Procedure:
4,5,6,7-Tetrahydrobenzo[b]thiophene (0.252 g, 1.79 mmol) was dissolved in chloroform (10 mL), cooled to 0° C. and N-bromosuccinimide (0.334 g, 1.88 mmol) was added. The reaction mixture was stirred at 0° C. for 1 h then at ambient temperature for 1.75 h and then heated at 40° C. for a further 4 h. The reaction mixture was cooled to room temperature, concentrated in vacuo and the residue diluted with water and extracted with diethyl ether (4×10 mL). The combined organic phase was washed with water and brine, dried over sodium sulfate, filtered and evaporated to afford the title compound (0.35 g, 88%) as a brown oil. NMR (CDCl3, 300 MHz): 6.69 (s, 1H), 2.73-2.59 (m, 2H), 2.58-2.49 (m, 2H), 1.88-1.70 (m, 4H).