Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.[B].C(S)[CH2:13][CH2:14][SH:15].Cl[CH2:18]Cl>>[CH2:18]1[O:10][C:8]([C:5]2[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=2)([CH3:9])[S:15][CH:14]1[CH3:13]
Reactant: CC(=O)c1ccc(C)cc1
Reactant: ClCCl
Reactant: SCCCS
Agent: [B]
Product: Cc1ccc(C2(C)OCC(C)S2)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A solution of 4′-methylacetophenone (10 g, 74.5 mmol) and dichloromethane (200 mL) was treated dropwise with boron trifluoroetherate (12.5 mL, 104 mmol) at room temperature. To the resulting solution was added 1,3-propanedithiol (7.45 mL, 74.5 mmol) and the reaction mixture was stirred for 4 h at room temperature. The reaction was quenched carefully with saturated NaHCO3 solution and extracted with dichloromethane. The organic layer was separated and evaporated in vacuo. The residue was dissolved in ethyl acetate and washed with 1 N NaOH, water, and saturated NaCl solution. The organic layer was separated, dried with MgSO4, filtered and solvent evaporated in vacuo to yield a crude oil. Purification of the crude oil via flash chromatography (50% CH2Cl2/hexane) afforded crystalline 4′-methylacetophenone propylene thioketal.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].CN(CN(C)C)C.[CH3:12][N:13]1[C:25]2[CH2:24][CH2:23][CH2:22][C:21](=O)[C:20]=2[C:19]2[C:14]1=C[CH:16]=[CH:17][CH:18]=2.[CH3:27][C:28]1[NH:29][CH:30]=[CH:31][N:32]=1>C(#N)C.C1(C)C=CC=CC=1>[CH3:12][N:13]1[C:14]2[CH2:19][CH2:18][CH:17]([CH2:16][N:29]3[CH:30]=[CH:31][N:32]=[C:28]3[CH3:27])[C:1](=[O:3])[C:2]=2[C:20]2[C:25]1=[CH:24][CH:23]=[CH:22][CH:21]=2
Reactant: CC(=O)Cl
Reactant: Cn1c2c(c3ccccc31)C(=O)CCC2
Reactant: Cc1ncc[nH]1
Agent: CN(C)CN(C)C
Solvent: CC#N
Solvent: Cc1ccccc1
Product: Cc1nccn1CC1CCc2c(c3ccccc3n2C)C1=O
Reaction time: 0.17 h
Yield: 81.5 %

Procedure:
To the solution of 36 ml of acetyl chloride in 50 ml of actonitrile and 750 ml of toluene, was slowly added 51 ml of N,N,N′,N′-tetramethyldiaminomethane at 0° C., which was then stirred for 10min. 50 g of 1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one and 100 g of 2-methyl imidazole was subsequently added to the reaction mixture, which was then stirred under reflux. After completion of reaction, the reaction mixture was evaporated, and then 150 ml of water was added to the resulting residue. The resulting solid was filtered and washed, and then dried under a reduced pressure. The resulting solid was suspended in 350 ml of methanol, and then 0.7 g of active carbon was added to thereto, which was then stirred for 1 hour under reflux. The resulting mixture was filtered and washed with methanol, which was then stirred for 3 hours at room temperature. The resulting solid was filtered and dried to give 60 g of pure white title compound (yield 81.5%).
Reaction SMILES: [F:1][C:2]1[C:7]([C:8]2[NH:12][CH:11]=[C:10]([CH:13]=[O:14])[CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[O-]S(C(F)(F)[F:20])(=O)=O.F[N+]1C(Cl)=CC=CC=1Cl>C(#N)C.O1CCCC1.C(=O)([O-])O.[Na+]>[F:20][C:9]1[C:10]([CH:13]=[O:14])=[CH:11][NH:12][C:8]=1[C:7]1[C:2]([F:1])=[N:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=S(=O)([O-])C(F)(F)F
Reactant: O=Cc1c[nH]c(-c2cccnc2F)c1
Agent: F[n+]1c(Cl)cccc1Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC#N
Product: O=Cc1c[nH]c(-c2cccnc2F)c1F
Reaction time: 2 h
Yield: 15.2 %

Procedure:
5-(2-Fluoropyridin-3-yl)-1H-pyrrole-3-carbaldehyde (660 mg) was dissolved in acetonitrile (30 mL) and tetrahydrofuran (30 mL), 1-fluoro-2,6-dichloropyridinium triflate (1.32 g) was added, and the mixture was stirred for 2 hr. The reaction mixture was diluted with saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=3:2→3:7) to give the title compound as pale-yellow crystals (yield 110 mg, 15%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:10](Br)=[C:9]([S:12]([C:15]3[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([C:22]#[N:23])[CH:16]=3)(=[O:14])=[O:13])[S:8][C:5]2=[N:6][CH:7]=1.C(O)C.[F:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.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>[NH2:1][C:2]1[CH:3]=[C:4]2[C:10]([C:32]3[CH:31]=[CH:30][CH:29]=[C:28]([F:27])[CH:33]=3)=[C:9]([S:12]([C:15]3[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([C:22]#[N:23])[CH:16]=3)(=[O:14])=[O:13])[S:8][C:5]2=[N:6][CH:7]=1
Reactant: N#Cc1cc(F)cc(S(=O)(=O)c2sc3ncc(N)cc3c2Br)c1
Reactant: OB(O)c1cccc(F)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: N#Cc1cc(F)cc(S(=O)(=O)c2sc3ncc(N)cc3c2-c2cccc(F)c2)c1
Yield: 7.6 %

Procedure:
5-Amino-3-bromo-2-(3-cyano-5-fluoro-benzenesulfonyl)-thieno[2,3-b]pyridine (1.2 g, 29 mmol) was dissolved in toluene (16 ml) and ethanol (18 ml) under argon atmosphere. To the solution Pd(PPh3)4 (157 mg, 0.14 mmol), 3-fluorophenylboronic acid (0.50 g, 35.8 mmol) and 2M solution of Na2CO3 (14 ml) was added. The reaction mixture was refluxed for 1 hour then it was filtered through celite and washed with toluene. The filtrate was tightened in vacuum; water (13 ml) and ethyl acetate (13 ml) were added to the residue. It was separated and the water phase was extracted with ethyl acetate (2×5 ml). The organic phase was washed with water (5.0 ml), dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography (Kieselgel 60, ethyl acetate:hexane=2:1) to yield 0.94 g (76%) of the title compound. The crude product can be purified by stirring with methanol to give a yellow amorphous material. LC-MS: (M+H)+ 428.2. 1H NMR (500 MHz, DMSO-d6, 25° C.): 5.67 (s, 2H); 6.81 (d, J=2.6 Hz, 1H); 7.00-7.07 (m, 2H); 7.35-7.43 (m, 1H); 7.50-7.60 (m, 2H); 7.60-7.64 (m, 1H); 8.20-8.25 (m, 1H); 8.27 (d, J=2.6 Hz, 1H).
Reaction SMILES: [C:1]([Cl:4])(=[O:3])[CH3:2].[CH3:5][N:6]([CH:14]1[CH2:18][CH:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:16]([CH2:25][N:26]2[CH2:31][CH2:30][CH:29]([N:32]([C:36](NCC3C=CC=CC=3)=[O:37])[CH2:33][CH2:34][CH3:35])[CH2:28][CH2:27]2)[CH2:15]1)C(OC(C)(C)C)=O>CO>[ClH:4].[ClH:4].[CH3:5][NH:6][CH:14]1[CH2:18][CH:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:16]([CH2:25][N:26]2[CH2:27][CH2:28][CH:29]([N:32]([C:36]([O:3][CH2:1][C:2]3[CH:17]=[CH:18][CH:14]=[CH:15][CH:16]=3)=[O:37])[CH2:33][CH2:34][CH3:35])[CH2:30][CH2:31]2)[CH2:15]1
Reactant: CC(=O)Cl
Reactant: CCCN(C(=O)NCc1ccccc1)C1CCN(CC2CC(N(C)C(=O)OC(C)(C)C)CC2c2ccccc2)CC1
Solvent: CO
Product: CCCN(C(=O)OCc1ccccc1)C1CCN(CC2CC(NC)CC2c2ccccc2)CC1
Product: Cl
Reaction time: 0.25 h
Yield: 2000 %

Procedure:
A solution of hydrogen chloride (2.3 mmol) in methanol was prepared by addition of acetyl chloride (0.165 mL, 2.3 mmol) to methanol (10 mL) and aging for 15 min. To this was added 1-(RS)-(N-(methyl)-N-(t-butoxycarbonyl)amino)-3-(SR)-((4-(N-(benzylaminocarbonyl)-N-(propyl)amino)piperidin-1-yl)methyl)-4-(SR)-phenylcyclopentane from Example 15 (135 mg, 0.23 mmol). After 16 h, the volatiles were removed in vacuo to dryness to give the title compound hydrochloride salt.
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.[Cl:13][C:14]1[S:18][C:17]([C:19]([NH:21][C:22]2[CH:30]=[CH:29][CH:28]=[C:27]3[C:23]=2[C:24](=[O:32])[NH:25][C:26]3=[O:31])=[O:20])=[CH:16][CH:15]=1.O[CH2:34][C:35]1[CH:36]=[C:37]([CH:47]=[CH:48][CH:49]=1)[CH2:38][NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.O>[Cl:13][C:14]1[S:18][C:17]([C:19]([NH:21][C:22]2[CH:30]=[CH:29][CH:28]=[C:27]3[C:23]=2[C:24](=[O:32])[N:25]([CH2:34][C:35]2[CH:36]=[C:37]([CH:47]=[CH:48][CH:49]=2)[CH2:38][NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:43])[CH3:44])[C:26]3=[O:31])=[O:20])=[CH:16][CH:15]=1
Reactant: CC(C)(C)OC(=O)NCc1cccc(CO)c1
Reactant: O=C(Nc1cccc2c1C(=O)NC2=O)c1ccc(Cl)s1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NCc1cccc(CN2C(=O)c3cccc(NC(=O)c4ccc(Cl)s4)c3C2=O)c1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
2.41 ml (15.4 mmol) of diethyl azodicarboxylate (DEAD) are added dropwise to a mixture, cooled with water, of 3.37 g (11 mmol) of 5-chloro-N-(1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl)-2-thiophenecarboxamide, 3.26 g (13.8 mmol) of tert-butyl 3-(hydroxymethyl)benzylcarbamate and 4.04 g (15.4 mmol) of triphenylphosphine in 60 ml of absolute THF. The reaction mixture is stirred vigorously at room temperature for 90 min and then concentrated to a volume of about 30 ml. 300 ml of ether are added to the solid and the mixture is filtered. Another crystallization of the mother liquor yields a second batch. The product is dried under high vacuum. Alternatively, the product can be purified by column chromatography on silica gel (dichloromethane/methanol mixture or cyclohexane/ethyl acetate mixture). Yield: 4.79 g (82.8% of theory);
Reaction SMILES: [CH3:1][C:2]1[C:7](=[O:8])[CH:6]([OH:9])[CH2:5][C:4]([CH3:11])([CH3:10])[C:3]=1[CH:12]=[CH:13][C:14]([CH3:18])=[CH:15][CH:16]=[O:17].N1C=CC=CC=1.[O:25]([CH2:32][C:33](Cl)=[O:34])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.O>C(OCC)C>[CH3:1][C:2]1[C:7](=[O:8])[C@@H:6]([O:9][C:33](=[O:34])[CH2:32][O:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:5][C:4]([CH3:10])([CH3:11])[C:3]=1[CH:12]=[CH:13][C:14]([CH3:18])=[CH:15][CH:16]=[O:17]
Reactant: CC(C=CC1=C(C)C(=O)C(O)CC1(C)C)=CC=O
Reactant: O=C(Cl)COc1ccccc1
Solvent: c1ccncc1
Solvent: O
Solvent: CCOCC
Product: CC(C=CC1=C(C)C(=O)[C@@H](OC(=O)COc2ccccc2)CC1(C)C)=CC=O
Temperature: 0 °C
Reaction time: 2 h

Procedure:
14 g of the hydroxyketoaldehyde of formula XIII obtained in Example 26 are dissolved in 200 ml of diethyl ether. 20 ml of pyridine are added to the solution at 0° C. and 12 g of phenoxyacetic acid chloride are then added dropwise. The mixture is stirred for 2 hours at 0° C. and then poured into water and extracted with diethyl ether. The 5-[2,6,6-trimethyl-3-oxo-4(S)-(phenoxyacetoxy)-cyclohex-1-en-1-yl]-3-methyl-penta-2,4-dien-1-al (IIA) is isolated from the ether extract.
Reaction SMILES: C(O[C:6]([N:8]1[CH2:12][C:11](=[N:13][O:14][CH3:15])[CH2:10][C@H:9]1[C:16]([OH:18])=O)=[O:7])(C)(C)C.[N:19]([CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=C=O.[CH2:27]([N:29]1[C:41]2[CH:40]=[CH:39][C:38]([NH2:42])=[CH:37][C:36]=2[C:35]2[C:30]1=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH3:28]>>[CH2:27]([N:29]1[C:41]2[CH:40]=[CH:39][C:38]([NH:42][C:16]([C@@H:9]3[CH2:10][C:11](=[N:13][O:14][CH3:15])[CH2:12][N:8]3[C:6]([NH:19][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[O:7])=[O:18])=[CH:37][C:36]=2[C:35]2[C:30]1=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH3:28]
Reactant: CCCCCN=C=O
Reactant: CCn1c2ccccc2c2cc(N)ccc21
Reactant: CON=C1C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)C1
Product: CCCCCNC(=O)N1CC(=NOC)C[C@H]1C(=O)Nc1ccc2c(c1)c1ccccc1n2CC

Procedure:
Following the general method as outlined in Example 22, starting from (2S,4EZ)-1-(tert-butoxycarbonyl)-4-(methoxyimino)-2-pyrrolidinecarboxylic acid, 1-isocyanatopentane, and 9-ethyl-9H-carbazol-3-amine the title compound was obtained in 81% purity by LC/MS. MS(ESI+): m/z=464.2.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([N:7]2[CH2:12][CH2:11][CH:10]([NH:13]C(=O)OC(C)(C)C)[CH2:9][CH2:8]2)[N:2]=1.Cl.O1CCOCC1>C1COCC1.CO>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([N:7]2[CH2:12][CH2:11][CH:10]([NH2:13])[CH2:9][CH2:8]2)[N:2]=1
Reactant: CC(C)(C)OC(=O)NC1CCN(c2cccnn2)CC1
Agent: Cl
Solvent: C1COCCO1
Solvent: CO
Solvent: C1CCOC1
Product: NC1CCN(c2cccnn2)CC1
Yield: 152.5 %

Procedure:
tert-Butyl (1-pyridazin-3-ylpiperidin-4-yl)carbamate (0.22 g, 0.92 mmol) was dissolved in THF:MeOH 70:30 (15 ml) and HCl in 1,4-dioxane (4M, 1.84 ml, 7.36 mmol) was added and the mixture was refluxed for 1.5 h. The reaction mixture was evaporated to yield the title compound (0.250 g, 100%) as the dihydrochloric salt. (0.250 g, 100%). 1H NMR (CD3OD, 500 MHz): δ 8.72-8.67 (m, 1H), 8.14-8.07 (m, 1H), 8.03-7.97 (m, 1H), 4.55-4.45 (m, 2H), 3.62-3.51 (m, 1H), 3.38-3.27 (m, 2H), 2.27-2.18 (m, 2H), 1.82-1.70 (m, 2H)
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[C:9]([C:11]([Cl:13])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([Cl:6])=[O:5].[C:14](OCCC)(=O)[C:15]1C=CC(C([O-])=O)=CC=1.[K+].S(Cl)(Cl)=O>C1(C)C=CC=CC=1>[CH2:1]([C:2]1[CH:10]=[C:9]([C:11]([Cl:13])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([Cl:6])=[O:5])[CH2:14][CH3:15]
Reactant: CCCOC(=O)c1ccc(C(=O)[O-])cc1
Reactant: Cc1cc(C(=O)Cl)ccc1C(=O)Cl
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: O=S(Cl)Cl
Product: CCCc1cc(C(=O)Cl)ccc1C(=O)Cl

Procedure:
This compound was prepared by the procedure described for monomethyl terephthaloyl chloride. Typical reagent levels were as follows: potassium monopropyl terephthalate (49.0g, 0.20 mole), thionyl chloride (29.8g, 0.25 mole) and 100 ml of toluene. The product was used without further purification.
Reaction SMILES: CI.[CH:3]1[C:19]2[C:18]3CC4[C:15]5[CH:20]=[CH:21][CH:22]=[CH:23][C:14]=5[CH:13]=[CH:12][C:11]=4[C:10]=3[CH:9]=[CH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.[CH3:24][C:25]([CH3:28])([O-])[CH3:26].[K+].CS(C)=O>O>[CH3:24][C:25]1([CH3:28])[C:18]2[C:19]3[CH:3]=[CH:4][CH:5]=[CH:6][C:7]=3[CH:8]=[CH:9][C:10]=2[C:11]2[CH:12]=[CH:13][C:14]3[CH:15]=[CH:20][CH:21]=[CH:22][C:23]=3[C:26]1=2
Reactant: CC(C)(C)[O-]
Reactant: c1ccc2c3c(ccc2c1)-c1ccc2ccccc2c1C3
Agent: [K+]
Solvent: CS(C)=O
Solvent: CI
Solvent: O
Product: CC1(C)c2c(ccc3ccccc23)-c2ccc3ccccc3c21
Reaction time: 10 h
Yield: 58.7 %

Procedure:
Methyl iodide 9.88 g (69.6 mmol) was dropwise added to a mixed solution of 6.18 g (23.2 mmol) of 13H-dibenzo[a,i]fluorene, 11.72 g (104.4 mmol) of potassium t-butoxide and 100 ml of dimethylsulfoxide at 20° C. in 20 minutes, and the solution was stirred for 10 hours. After left standing overnight, 9.88 g (69.6 mmol) of methyl iodide was further dropwise added and stirred for 5 hours. Water was dropwise added to the reaction mixture, and the solution was extracted with dichloromethane. After separating the solution, the organic phase was concentrated and refined by flash chromatograph (silica gel: hexane/dichloromethane=5/1) to obtain 4.01 g (yield: 58.7%) of 13,13-dimethyl-13H-dibenzo[a,i]fluorene.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[N:15]([C:16]=1[C:17]1[CH:22]=[CH:21][N:20]=[C:19]([S:23][CH3:24])[N:18]=1)[CH:14]=[CH:13][O:12]2.[OH:25]OS([O-])=O.[K+]>CO.C(Cl)Cl.O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[N:15]([C:16]=1[C:17]1[CH:22]=[CH:21][N:20]=[C:19]([S:23]([CH3:24])=[O:25])[N:18]=1)[CH:14]=[CH:13][O:12]2
Reactant: CSc1nccc(-c2c(-c3ccc(F)cc3F)nc3occn23)n1
Reactant: O=S([O-])OO
Agent: [K+]
Solvent: CO
Solvent: ClCCl
Solvent: O
Product: CS(=O)c1nccc(-c2c(-c3ccc(F)cc3F)nc3occn23)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 96 %

Procedure:
A round bottom flask was charged with 6-(2,4-difluorophenyl)-5-(2-(methylthio)pyrimidin-4-yl)imidazo[2,1-b]oxazole (0.16 g, 0.47 mmol) and OXONE® (0.312 g, 0.508 mmol). The reaction mixture was diluted with MeOH (10.0 mL), DCM (10.0 mL) and water (2.0 mL). The reaction mixture was stirred at ambient temperature for about 8 h. The reaction mixture was quenched with water (100 mL) and extracted with DCM (2×200 mL). The organic phase was washed with H2O (100 mL) then dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography using a gradient of 10-100% EtOAc in heptane and then a gradient of 0-20% MeOH in DCM to give the title compound (0.16 g, 96%). LC/MS (Table 1, Method o) Rt=2.63 min; MS m/z 361.1.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[N:8]([C:13]1[CH:18]=[C:17]([N+:19]([O-])=O)[C:16]([F:22])=[C:15]([F:23])[C:14]=1[F:24])[CH:7]=[C:6]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[C:5]2=[O:30].C(O)(=O)C.ClC(Cl)C>C(O)C.[Pd]>[NH2:19][C:17]1[CH:18]=[C:13]([N:8]2[C:9]3[C:4](=[CH:3][C:2]([F:1])=[C:11]([F:12])[CH:10]=3)[C:5](=[O:30])[C:6]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:7]2)[C:14]([F:24])=[C:15]([F:23])[C:16]=1[F:22]
Reactant: CCOC(=O)c1cn(-c2cc([N+](=O)[O-])c(F)c(F)c2F)c2cc(F)c(F)cc2c1=O
Agent: [Pd]
Solvent: CCO
Solvent: CC(=O)O
Solvent: CC(Cl)Cl
Product: CCOC(=O)c1cn(-c2cc(N)c(F)c(F)c2F)c2cc(F)c(F)cc2c1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 76.8 %

Procedure:
Ethyl 6,7-difluoro-1,4-dihydro-4-oxo-1-(2,3,4-trifluoro-5-nitrophenyl)quinoline-3-carboxylate (280 mg) was dissolved in 10 ml of ethanol, 5 ml of acetic acid, and 5 ml of dichloroethane, to which was added 30 mg of 10% palladium on carbon. Under a hydrogen atmosphere, the solution was stirred overnight at room temperature. The catalyst was removed by a membrane filter and the filtrate was concentrated in vacua. Ethanol was added to the residue whereupon the solid was collected by filtration and washed with diethyl ether to give 200 mg of the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:20])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14](Cl)=[O:15])=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18].[F:21][C:22]1[CH:28]=[CH:27][C:25]([NH2:26])=[CH:24][CH:23]=1>>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:20])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14]([NH:26][C:25]2[CH:27]=[CH:28][C:22]([F:21])=[CH:23][CH:24]=2)=[O:15])=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18]
Reactant: O=C(Cl)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1
Reactant: Nc1ccc(F)cc1
Product: O=C(Nc1ccc(F)cc1)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1

Procedure:
Prepared according to the procedure described for example 50 from 5-[(3,5-dichloro-4-pyridyl)sulfanyl]-4-nitro-thiophene-2-carbonyl chloride (120 mg, 0.33 mmol) and 4-fluoro-aniline (43 mg, 0.39 mmol). The title compound was obtained as a solid (60 mg, 41% yield). 1H NMR (400 MHz, d6-DMSO) δ: 10.58 (1H, s), 9.00 (2H, s), 8.69 (1H, s), 7.67 (2H, m), 7.21 (2H, m). MS m/z: 442.06, 444.06 [M+H]+.
Reaction SMILES: [H-].[Na+].[OH:3][CH2:4][C:5]1[N:6]=[C:7]([C:10]2[N:11](COCC[Si](C)(C)C)[CH:12]=[C:13]3[C:18]=2[C:17](=[O:19])[N:16]([CH3:20])[C:15](=[O:21])[N:14]3[CH3:22])[S:8][CH:9]=1.[CH3:31][O:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37]Cl)=[CH:35][CH:34]=1>CN1C(=O)CCC1>[CH3:31][O:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37][O:3][CH2:4][C:5]2[N:6]=[C:7]([C:10]3[NH:11][CH:12]=[C:13]4[C:18]=3[C:17](=[O:19])[N:16]([CH3:20])[C:15](=[O:21])[N:14]4[CH3:22])[S:8][CH:9]=2)=[CH:35][CH:34]=1
Reactant: COc1ccc(CCl)cc1
Reactant: Cn1c(=O)c2c(-c3nc(CO)cs3)n(COCC[Si](C)(C)C)cc2n(C)c1=O
Agent: [H-]
Agent: [Na+]
Solvent: CN1CCCC1=O
Product: COc1ccc(COCc2csc(-c3[nH]cc4c3c(=O)n(C)c(=O)n4C)n2)cc1
Reaction time: 1 h

Procedure:
Sodium hydride (60% wt, 0.637 g, 15.93 mmol) was added portionwise to a solution of 5-(4-(hydroxymethyl)thiazol-2-yl)-1,3-dimethyl-6-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (step 2) (4.43 g, 7.97 mmol) NMP (Volume: 44 ml) at 0° C. and stirred for 1 hour. para-Methoxybenzyl chloride (1.404 ml, 10.36 mmol) was added and the mixture stirred at room temperature for 5 hours. Further portions of para-methoxybenzyl chloride (220 μl) and sodium hydride (60% wt, 64 mg) were added and the mixture stirred for a further 16 hours. The reaction was quenched at 0° C. with saturated NaHCO3(aq) (50 ml), diluted with water (200 ml) and EtOAc (100 ml) and the phases separated. The aqueous phase was extracted with EtOAc (3×100 ml). The combined organic extracts were washed with water (2×100 ml) and brine (100 ml), dried over sodium sulfate and evaporated under vacuum. Purification by chromatography on silica, eluting with 40-60% EtOAc/hexane afforded the title compound and 5-(4-(((4-methoxybenzyl)oxy)methyl)thiazol-2-yl)-1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione as a mixture which was used without further purification.
Reaction SMILES: [Cl:1][C:2]1[C:10]([S:11]([CH3:14])(=[O:13])=[O:12])=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([O:15][CH2:16][CH3:17])[CH:3]=1.[N+](=[CH2:20])=[N-]>O1CCCC1.CCOCC>[CH3:20][O:7][C:6](=[O:8])[C:5]1[CH:9]=[C:10]([S:11]([CH3:14])(=[O:12])=[O:13])[C:2]([Cl:1])=[CH:3][C:4]=1[O:15][CH2:16][CH3:17]
Reactant: CCOc1cc(Cl)c(S(C)(=O)=O)cc1C(=O)O
Reactant: C=[N+]=[N-]
Solvent: CCOCC
Solvent: C1CCOC1
Product: CCOc1cc(Cl)c(S(C)(=O)=O)cc1C(=O)OC
Reaction time: 0.17 h

Procedure:
A solution of 4-chloro-2-ethoxy-5-methanesulfonylbenzoic acid (2.5 g, 9.0 mmol) in tetrahydrofuran was cooled to 5° C. and treated with excess diazomethane in ether solution (prepared from N-methyl-N-nitroso-p-toluenesulfonamide, Aldrich) and stirred for 10 min. Solvent and excess diazomethane was removed by rotary evaporation. The resulting residue was dissolved in dichloromethane and filtered through a plug of silica gel and evaporated. The solids were triturated with ether/hexane to give 4-chloro-2-ethoxy-5-methanesulfonyl-benzoic acid methyl ester (2.1 g, colorless solids).
Reaction SMILES: [C:1]1([C:7]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:8][CH2:9][CH:10]([N:12]=[C:13]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH3:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H][H].C(OCC)C>C(O)(=O)C.C(O)C.[Pt]=O>[C:1]1([CH:7]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[NH:8][CH2:9][CH:10]([NH:12][CH:13]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH3:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(CN=C(c1ccccc1)c1ccccc1)N=C(c1ccccc1)c1ccccc1
Reactant: [H][H]
Agent: O=[Pt]
Solvent: CCOCC
Solvent: CC(=O)O
Solvent: CCO
Product: CC(CNC(c1ccccc1)c1ccccc1)NC(c1ccccc1)c1ccccc1

Procedure:
180 g of N,N'-bis-(diphenylmethylene)-1,2-propylenediamine are dissolved in 540 ml of acetic acid. 3 g of platinum oxide are added and the mixture is scavenged thoroughly with argon and then hydrogen is introduced while stirring vigorously until starting material can no longer be detected by thin layer chromatography (silica gel 60, diethyl ether: Rf =0.62) (generally 24 to 48 hours). The reaction solution is diluted with 150 ml of ethanol, the catalyst is filtered off and then the filtrate is concentrated to dryness by evaporation under reduced pressure in a water bath. The oil residue obtained after concentration by evaporation is triturated with 375 ml of 10% sodium hydroxide solution and extracted twice with 375 ml of diethyl ether each time. The ether phases are combined, washed twice with 70 ml of saturated sodium chloride solution each time, dried over magnesium sulphate and then evaporated to dryness on a water bath, first at approximately 20 mbar and then at approximately 0.03 mbar. The residue is dissolved in approximately 300 ml of ethanol, water is added until the solution starts to become cloudy (approximately 20 ml) and then the whole is caused to crystallise in an ice bath. The precipitated crystals are filtered with suction, washed with a little methanol and dried thoroughly at approximately 0.03 mbar. N,N'-bis-(diphenylmethyl)-1,2-propylenediamine having a melting point of 72°-75° C. is obtained which can be further purified by recrystallisation from approximately double the quantity of methanol and by precipitation with water, and then melts at 75°-77° C.