Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Si]([O:8][C@H:9]([C:36]1[CH:41]=[CH:40][C:39]([OH:42])=[C:38]([CH2:43][OH:44])[CH:37]=1)[CH2:10][NH:11][C@H:12]([CH3:35])[CH2:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[NH:19][C:18]([C:23]([NH:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[O:33][CH3:34])=[O:24])=[CH:17]2)(C(C)(C)C)(C)C.[F-].[NH4+]>CO.O>[OH:8][C@H:9]([C:36]1[CH:41]=[CH:40][C:39]([OH:42])=[C:38]([CH2:43][OH:44])[CH:37]=1)[CH2:10][NH:11][C@H:12]([CH3:35])[CH2:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[NH:19][C:18]([C:23]([NH:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[O:33][CH3:34])=[O:24])=[CH:17]2
Reactant: COc1ccccc1CNC(=O)c1cc2cc(C[C@@H](C)NC[C@H](O[Si](C)(C)C(C)(C)C)c3ccc(O)c(CO)c3)ccc2[nH]1
Agent: [F-]
Agent: [NH4+]
Solvent: O
Solvent: CO
Product: COc1ccccc1CNC(=O)c1cc2cc(C[C@@H](C)NC[C@H](O)c3ccc(O)c(CO)c3)ccc2[nH]1
Temperature: 40 °C
Yield: 68.6 %

Procedure:
A solution of 5-[(2R)-2-({(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino)propyl]-N-(2-methoxybenzyl)-1H-indole-2-carboxamide (Preparation 1, 67 mg, 0.11 mmol) in a mixture of methanol (4.0 ml) and water (2.4 ml) was treated with ammonium fluoride (40 mg, 1.08 mmol) and the resulting suspension heated at 40° C. for a period of 16 hours. The solvent was removed in vacuo and the residue purified by flash column chromatography on silica gel eluting with dichloromethane:methanol 0.88 ammonia (95:5:0.5 changing to 85:15:1.5, by volume) to give the title compound as a colourless solid (38 mg).
Reaction SMILES: [CH3:1][C:2]1[N:10]([CH:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH3:12])[C:5]2=[CH:6][N:7]=[CH:8][CH:9]=[C:4]2[C:3]=1[C:19]([O:21]C)=[O:20].[OH-].[K+].Cl>O>[CH3:1][C:2]1[N:10]([CH:11]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH3:12])[C:5]2=[CH:6][N:7]=[CH:8][CH:9]=[C:4]2[C:3]=1[C:19]([OH:21])=[O:20]
Reactant: COC(=O)c1c(C)n(C(C)c2ccccc2)c2cnccc12
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: Cc1c(C(=O)O)c2ccncc2n1C(C)c1ccccc1
Yield: 100 %

Procedure:
To a mixture of methyl 2-methyl-1-(1-phenylethyl)-1H-pyrrolo[2,3-c]pyridine-3-carboxylate (800 mg, 2.72 mmol) and KOH (1.5 g, 27.2 mmol) in (15 mL) and water (5 mL) was refluxed for 2 hours. The mixture was adjust PH to 2 by 10% HCl and extracted with EA. The combined organic layers were washed with brine, dried and concentrated to afford the crude product. The crude product was used into the next step without more purification. 100% yield. (760 mg).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([B:8]2[O:16][C:13]([CH3:15])([CH3:14])[C:10]([CH3:12])([CH3:11])[O:9]2)=[C:4]([F:17])[CH:3]=1.C(=O)([O-])O.[Na+].Cl[C:24]([O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:25]>C1COCC1>[C:27]1([O:26][C:24](=[O:25])[NH:1][C:2]2[CH:7]=[CH:6][C:5]([B:8]3[O:9][C:10]([CH3:12])([CH3:11])[C:13]([CH3:15])([CH3:14])[O:16]3)=[C:4]([F:17])[CH:3]=2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: CC1(C)OB(c2ccc(N)cc2F)OC1(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: CC1(C)OB(c2ccc(NC(=O)Oc3ccccc3)cc2F)OC1(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred solution of 4-amino-2-fluorophenyl boronic acid pinacol ester (3.0 g, 12.7 mmol) in THF (10 ml) was added sodium hydrogen carbonate (1.6 g, 19.0 mmol) followed by phenyl chloroformate (1.9 ml, 15.2 mmol) and stirred overnight at room temperature. The reaction mixture was partitioned between DCM and water, the organic phase recovered, dried over Mg2SO4 and filtered before being concentrated in-vacuo to afford a white solid (4.95 g, quantitative).
Reaction SMILES: [OH-].[Na+].[F:3][C:4]1[CH:25]=[C:24]([CH3:26])[C:23]([O:27]C(OC)=O)=[CH:22][C:5]=1[NH:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][CH2:18][CH2:19][O:20][CH3:21])=[CH:14][CH:15]=2)[N:10]=[CH:9][N:8]=1.[ClH:32]>CO.O>[ClH:32].[F:3][C:4]1[CH:25]=[C:24]([CH3:26])[C:23]([OH:27])=[CH:22][C:5]=1[NH:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][CH2:18][CH2:19][O:20][CH3:21])=[CH:14][CH:15]=2)[N:10]=[CH:9][N:8]=1
Reactant: COCCNc1ccc2c(Nc3cc(OC(=O)OC)c(C)cc3F)ncnc2c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COCCNc1ccc2c(Nc3cc(O)c(C)cc3F)ncnc2c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 90 %

Procedure:
2M Aqueous sodium hydroxide solution (760 μl, 1.5 mmol) was added to a solution of 4-(2-fluoro-5-methoxycarbonyloxy4-methylanilino)-7-(2-methoxyethylamino)quinazoline (304 mg, 0.76 mmol) in methanol (8 ml) at 5° C. and the mixture then stirred for 30 minutes at ambient temperature. The mixture was diluted with water and adjusted to pH6 with 2M hydrochloric acid. The precipitated solid was collected by filtration and then suspended in methylene chloride/methanol. A 5M solution of hydrogen chloride in isopropanol (0.4 ml) was added and the volatiles were removed from the resulting solution by evaporation. The residue was triturated with ether, the solid product collected by filtration, washed with ether and dried under vacuum to give 4-(2-fluoro-5-hydroxy-4-methylanilino)-7-(2-methoxyethylamino)quinazoline hydrochloride (260 mg, 90%) as yellow solid.
Reaction SMILES: [C:1]([C:3]1[C:20]([F:21])=[CH:19][C:6]([O:7][CH2:8][C@@H:9]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH3:10])=[CH:5][C:4]=1[F:22])#[CH:2].Br[C:24]1[CH:29]=[CH:28][C:27]([O:30][CH2:31][CH:32]2[CH2:34][CH2:33]2)=[CH:26][N:25]=1.C(N(CC)CC)C>C1(C)C=CC=CC=1.[Cu](I)I.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:32]1([CH2:31][O:30][C:27]2[CH:28]=[CH:29][C:24]([C:2]#[C:1][C:3]3[C:4]([F:22])=[CH:5][C:6]([O:7][CH2:8][C@@H:9]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:16])([CH3:17])[CH3:15])[CH3:10])=[CH:19][C:20]=3[F:21])=[N:25][CH:26]=2)[CH2:33][CH2:34]1
Reactant: Brc1ccc(OCC2CC2)cn1
Reactant: C#Cc1c(F)cc(OC[C@H](C)NC(=O)OC(C)(C)C)cc1F
Agent: Cl[Pd]Cl
Agent: I[Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: C[C@@H](COc1cc(F)c(C#Cc2ccc(OCC3CC3)cn2)c(F)c1)NC(=O)OC(C)(C)C
Temperature: 100 °C
Reaction time: 8 h
Yield: 35.9 %

Procedure:
A mixture of tert-butyl [(1S)-2-(4-ethynyl-3,5-difluorophenoxy)-1-methylethyl]carbamate (2.5 g), 2-bromo-5-(cyclopropylmethoxy)pyridine (1.8 g), copper iodide (I) (0.15 g), dichloropalladium-triphenylphosphine (1:2) (0.56 g) and triethylamine (2.2 mL) in toluene (20 mL) was stirred at 100° C. overnight under argon atmosphere. After cooling to room temperature, the mixture was filtered through a pad of Celite. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to afford the title compound (1.3 g).
Reaction SMILES: [C:1]1([CH2:7][O:8][CH:9]([CH2:14][CH:15]=[CH2:16])[CH:10]([OH:13])[CH2:11][OH:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)(O)[O-].[Na+].[I:22]I.S([O-])([O-])=O.[Na+].[Na+]>C(OCC)C.O>[I:22][CH2:16][C@H:15]1[O:13][C@H:10]([CH2:11][OH:12])[C@@H:9]([O:8][CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:14]1
Reactant: II
Reactant: C=CCC(OCc1ccccc1)C(O)CO
Agent: O=C([O-])O
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: CCOCC
Solvent: O
Product: OC[C@H]1O[C@H](CI)C[C@@H]1OCc1ccccc1
Temperature: 0 °C
Reaction time: 3 h
Yield: 99.3 %

Procedure:
A 0° C. solution of 4.5 g of product from Example 333 in 77.8 ml of diethyl ether and 25.5 ml of water is treated with 2.58 g of solid sodium bicarbonate followed by 7.6 g of iodine. The reaction is stirred for 3 hours at 0° C. then at room temperature overnight. The mixture is cooled to 0° C. and sodium sulfite is added until the reaction is colorless. The solution is extracted with diethyl ether, dried and concentrated in vacuo to give 7.0 g of an oil. The oil is purified by chromatography (Silica gel: 5% diethyl ether/hexane) to give 2.8 g of Isomer A and 1.86 g of Isomer B. Isomer A:
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@@H:9]([C@H:12]([O:14][CH3:15])[CH3:13])[CH2:10][OH:11])[CH:5]=[CH:4][N:3]=1.Cl[C:17](Cl)([O:19]C(=O)OC(Cl)(Cl)Cl)Cl.CC1C=CC=C(C)N=1.CCOC(C)=O.CCCCCCC>C(Cl)Cl.O>[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[C@@H:9]([C@H:12]([O:14][CH3:15])[CH3:13])[CH2:10][O:11][C:17]2=[O:19])[CH:5]=[CH:4][N:3]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: CO[C@H](C)[C@@H](CO)Nc1ccnc(Cl)n1
Solvent: CCCCCCC
Solvent: Cc1cccc(C)n1
Solvent: CCOC(C)=O
Product: CO[C@H](C)[C@H]1COC(=O)N1c1ccnc(Cl)n1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 28.1 %

Procedure:
To a round bottom flask containing (2R,3R)-2-((2-chloropyrimidin-4-yl)amino)-3-methoxybutan-1-ol (1.68 g, 3.63 mmol) and a stir bar under nitrogen was added DCM (18 mL). The resulting reaction mixture cooled to 0° C. in a brine/ice bath. To this cold solution was then added triphosgene (0.59 g, 1.99 mmol) followed by the addition of 2,6-dimethylpyridine (2 mL, 17.0 mmol). Resulting reaction mixture allowed to stir 30 min at 0° C. The reaction mixture was diluted with DCM and water and allowed to stir 1 hr at room temperature. The phases partitioned and the aqueous phase extracted with DCM. Organic phases were combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptane 0 to 100%) provided (R)-3-(2-chloropyrimidin-4-yl)-4-((R)-1-methoxyethyl)oxazolidin-2-one (145 mg, 0.56 mmol, 15% yield) as a white crystalline. 1H NMR (400 MHz, CDCl3) δ 1.09 (d, J=6.26 Hz, 3H) 3.45 (s, 3H) 4.15 (qd, J=6.39, 4.30 Hz, 1H) 4.39-4.47 (m, 1H) 4.60 (dd, J=9.39, 2.74 Hz, 1H) 5.02 (dt, J=8.61, 3.52 Hz, 1H) 8.17 (d, J=5.87 Hz, 1H) 8.48 (d, J=5.87 Hz, 1H). LCMS m/z 258.1 (M+H)+, Rt 0.69 min.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=1)(=[O:4])=[O:3].Br[C:15]1[N:16]=[CH:17][C:18]([O:21][CH2:22][CH:23]2[CH2:28][CH2:27][N:26]([C:29]([O:31][CH:32]([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]2)=[N:19][CH:20]=1.C([O-])([O-])=O.[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.COCCOC>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:15]2[N:16]=[CH:17][C:18]([O:21][CH2:22][CH:23]3[CH2:24][CH2:25][N:26]([C:29]([O:31][CH:32]([CH3:34])[CH3:33])=[O:30])[CH2:27][CH2:28]3)=[N:19][CH:20]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3]
Reactant: CC(C)OC(=O)N1CCC(COc2cnc(Br)cn2)CC1
Reactant: CS(=O)(=O)c1ccc(B(O)O)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: CC(C)OC(=O)N1CCC(COc2cnc(-c3ccc(S(C)(=O)=O)cc3)cn2)CC1

Procedure:
The title compound (0.303 g, 61%) was prepared as a white solid from [4-(methylsulfonyl)phenyl]boronic acid (0.28 g, 1.37 mmol), 1-methylethyl 4-{[(5-bromo-2-pyrazinyl)oxy]methyl}-1-piperidinecarboxylate (crude material prepared in Step 2), Pd(PPh3)2Cl2 (82 mg, 0.11 mmol), 2M Na2CO3 (8 mL) and DME (8 mL) in a manner similar to Example 21, Step 3. The crude material was purified by flash chromatography on a silica gel column eluted with 1:20 acetone/CH2Cl2 to 1:10 acetone/CH2Cl2 followed by trituration with hot hexanes containing 1% MeOH to give the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.56 (s, 1H), 8.31 (s, 1H), 8.12 (d, 2H, J=8.3 Hz), 8.03 (d, 2H, J=8.3 Hz), 4.92 (septet, 1H, J=6.2 Hz), 4.30-4.10 (m, 4H), 3.09 (s, 3H), 2.85-2.70 (m, 2H), 2.10-1.95 (m, 1H), 1.90-1.80 (m, 2H), 1.40-1.20 (m, 8H); LRMS (ESI), m/z 434 (M+H).
Reaction SMILES: C([O-])=O.[NH4+].[F:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[C:7]=1[C:13]1[NH:14][C:15]([C:24]2[CH:29]=[CH:28][C:27]([N+:30]([O-])=O)=[C:26]([NH:33][CH2:34][CH:35]([CH3:37])[CH3:36])[CH:25]=2)=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:17]=1>[Pd].C(O)C>[F:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[C:7]=1[C:13]1[NH:14][C:15]([C:24]2[CH:29]=[CH:28][C:27]([NH2:30])=[C:26]([NH:33][CH2:34][CH:35]([CH3:37])[CH3:36])[CH:25]=2)=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:17]=1
Reactant: CC(C)CNc1cc(-c2[nH]c(-c3c(F)cccc3F)nc2-c2ccccc2)ccc1[N+](=O)[O-]
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CCO
Product: CC(C)CNc1cc(-c2[nH]c(-c3c(F)cccc3F)nc2-c2ccccc2)ccc1N
Temperature: 60 °C
Yield: 98.8 %

Procedure:
Add ammonium formate (0.6 g, 9.6 mmol) followed by palladium on carbon (0.05 g, 0.48 mmol) to a solution of 2-(2,6-difluorophenyl-4-phenyl-5-(3-(isobutyl)amino-4-nitrophenyl)imidazole (1.0 g, 2.4 mmol) in 8 mL ethanol, and then heat the mixture to 60° C. for 3 hours. Cool the reaction mixture to room temperature, filter through celite, and concentrate the filtrate under reduced pressure to provide the title compound (0.99 g, 2.37 mmol)
Reaction SMILES: [CH3:1][C:2]([CH3:12])([CH2:5][N:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1)[CH2:3][OH:4].[CH3:13][S:14](Cl)(=[O:16])=[O:15]>ClCCl>[CH3:1][C:2]([CH3:12])([CH2:5][N:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1)[CH2:3][O:4][S:14]([CH3:13])(=[O:16])=[O:15]
Reactant: CC(C)(CO)CN1CCCCC1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Product: CC(C)(COS(C)(=O)=O)CN1CCCCC1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
A solution of 0.51 g (2.99 mmol) of 2,2-dimethyl-3-piperidin-1-yl-propan-1-ol in 7 ml of dichloromethane was treated at 0° C. with 0.24 ml (179.59 mmol) of methanesulfonyl chloride and stirred at RT for 2.5 h. The reaction was extracted with aqueous saturated NaHCO3 /Et2O (3×). The organic phases were washed with aqueous saturated NaHCO3, dried over Na2SO4 and evaporated to give 0.85 g (quantitative) of the title compound as light brown oil. MS: 249.2 (M+).
Reaction SMILES: [CH3:1][C:2]([OH:6])([C:4]#[CH:5])[CH3:3].[Si:7](OS(C(F)(F)F)(=O)=O)([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]>C(Cl)Cl>[C:10]([Si:7]([O:6][C:2]([CH3:3])([CH3:1])[C:4]#[CH:5])([CH3:9])[CH3:8])([CH3:13])([CH3:12])[CH3:11]
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Reactant: C#CC(C)(C)O
Solvent: ClCCl
Product: C#CC(C)(C)O[Si](C)(C)C(C)(C)C
Reaction time: 2 h
Yield: 79.3 %

Procedure:
2-Methyl-but-3-yn-2-ol (2.20 g, 26.2 mmol) in DCM (50 mL) was mixed with 2,6-lutadine (9.1 mL, 78.6 mmol). TBSOTf (6.6 mL, 28.8 mmol) was added to the reaction mixture slowly. After 2 hours at room temperature, an extra amount of TBSOTf (1.5 mL) was added. After 16 hours at room temperature, the reaction was quenched with 10% HOAc aqueous solution (400 mL). The product was extracted with DCM (2×200 mL). The combined organic layers were washed with brine, dried and concentrated. Purification of the crude on silica gel column (Foxy, 3:7 EtOAc/Hexane) provided desired product as colorless liquid (4.12 g, 80%). 1H NMR (CDCl3) δ 2.58 (s, 1H), 0.82 (s, 6H).
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@@:15]([CH2:25][O:26]S(C)(=O)=O)([CH2:16][O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:14][C@H:11]([O:12][CH3:13])[C@@H:10]1O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+]>CN(C=O)C>[CH2:1]([O:8][C@H:9]1[C@H:10]2[O:26][CH2:25][C@:15]1([CH2:16][O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[O:14][C@H:11]2[O:12][CH3:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CO[C@H]1O[C@@](COCc2ccccc2)(COS(C)(=O)=O)[C@@H](OCc2ccccc2)[C@H]1O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CO[C@@H]1O[C@@]2(COCc3ccccc3)CO[C@@H]1[C@@H]2OCc1ccccc1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
A solution of 201 (3.32 g, 7.34 mmol) in anhydrous DMF (25 mL) was stirred at 0° C. and a 60% oil dispersion of sodium hydride (700 mg, 16.9 mmol) was added. The mixture was stirred at room temperature for 90 min, quenched with water (300 mL) and extracted with diethyl ether (2×300 mL). The combined extract was washed with water (200 mL) and dried (MgSO4). The solvent was removed under reduced pressure and the residue was purified by chromatography over silica gel with dichloromethane as eluent to give the two products 202 and 203 as clear oils (1.571 g, 60% and 0.777 g, 30% respectively). (1S,3R,4R,7S)-7-Benzyloxy-1-benzyloxymethyl-3-methoxy-2,5-dioxabicyclo[2.2.1]heptane (202). 1H NMR (CDCl3): δ7.36-7.26 (10H, m, Bn), 4.81 (1H, s, H-1), 4.65 (1H, d, J 11.9 Hz, Bn), 4.61 (2H, s, Bn), 4.56 (1H, d, J 11.9 Hz, Bn), 4.11 (1H, s, H-2), 4.09 (1H, s, H-3), 4.01 (1H, d, J 7.5 Hz, H-5′), 3.80-3.77 (3H, m, H-5′, H-5), 3.39 (3H, s, OCH3); 13C NMR (CDCl3): δ138.05, 137.36, 128.47, 128.44, 127.88, 127.73, 127.63 (Bn), 104.97 (C-1), 85.13 (C-4), 79.16 (C-3), 77.18 (C-2), 73.64 (Bn), 72.26, 72.10 (Bn, C-5′), 66.50 (C-5), 55.34 (OCH3); MS FAB: 379 (M+Na, 28%), Found: C, 70.55; H, 6.97; C21H24O5 requires C, 70.77; H, 6.79%. (1S,3R,4R,7S)-7-Benzyloxy-1-benzyloxymethyl-3-methoxy-2,5-dioxabicyclo-[2.2.1]heptane (203). 1H NMR (CDCl3): δ7.36-7.26 (10H, m, Bn), 5.00 (1H, s, H-1), 4.67-4.54 (4H, m, Bn), 4.18 (1H, s, H-2), 3.99 (1H, s, H-3), 3.99-3.90 (2H, m, H-5′), 3.75-3.68 (2H, m, H-5), 3.49 (3H, s, OCH3); 13C NMR (CDCl3): δ137.83, 137.53, 128.51, 128.48, 127.96, 127.82, 127.71, 127.62 (Bn), 104.05 (C-1), 88.4 (C-4), 79.54 (C-3), 77.16 (C-2), 73.68 (Bn), 72.61 (C-5′), 72.24 (Bn), 65.73 (C-5), 56.20 (OCH3); MS FAB: 379 (M+Na, 100%).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:13][CH2:12][C:11]([CH2:14][PH:15](=[O:20])[O:16][CH:17]([CH3:19])[CH3:18])=[CH:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO.[Pt]=O>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:13][CH2:12][C@H:11]([CH2:14][PH:15](=[O:20])[O:16][CH:17]([CH3:18])[CH3:19])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)O[PH](=O)CC1=CC(NC(=O)OC(C)(C)C)CC1
Agent: O=[Pt]
Solvent: CO
Product: CC(C)O[PH](=O)C[C@H]1CC[C@@H](NC(=O)OC(C)(C)C)C1
Yield: 64.3 %

Procedure:
A solution of isopropyl (3-t-butyloxyaminocyclopentenyl)methylphosphinate (9) (3.4 g, 10.7 mmol) in methanol (30 cm3) was hydrogenated over platinum oxide (50 mg) at 40 psi for 3 h. The catalyst was removed by filtration through celite and then washed with methanol (3×30 cm3). The solvent was removed in vacuo and the crude product was purified by short column vacuum chromatography on silica gel (15% ethanol/ethyl acetate) to yield the desired cis isomer (10) as a colourless oil (2.1 g, 95%): 1H NMR (300 MHz, CDCl3) δ 1.24 (3H, 2×d, J=6.3 Hz, POCHCH3), 1.32 (3H, d, J=6.3 Hz, POCHCH3), 1.44 (9H, br. s, C(CH3)3), 1.48 and 1.49 (3H, d, J=14.7 and 14.1 Hz, PCH3), 1.58-1.75 (2H, m, C(2)—H, C(4)—H), 2.41-2.72 (5H, m, C(1)—H, C(2)—H′, C(4)—H′, C(5)—H and C(5)—H′), 4.53 (2H, m, POCHCH3 and NH), 4.84 (1H, br. m, C(3)—H),
Reaction SMILES: C([S:4][CH2:5][CH2:6][CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([C:17]2[C:18](=[O:33])[NH:19][C:20](=[O:32])[C:21]=2[C:22]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[N:24]([CH3:31])[CH:23]=2)=[CH:9]1)(=O)C.N>CO.CN(C=O)C.[Cl-].[Na+]>[SH:4][CH2:5][CH2:6][CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([C:17]2[C:18](=[O:33])[NH:19][C:20](=[O:32])[C:21]=2[C:22]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[N:24]([CH3:31])[CH:23]=2)=[CH:9]1
Reactant: CC(=O)SCCCn1cc(C2=C(c3cn(C)c4ccccc34)C(=O)NC2=O)c2ccccc21
Agent: N
Agent: [Cl-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CO
Product: Cn1cc(C2=C(c3cn(CCCS)c4ccccc34)C(=O)NC2=O)c2ccccc21
Reaction time: 17 h
Yield: 83.7 %

Procedure:
350 mg of the product of Example 99 in 20 ml of 50% methanol/DMF were treated with 0.5 ml of 33% aqueous ammonia. The mixture was stirred for 17 hours, then diluted with 20 ml of sodium chloride solution and extracted with ethyl acetate. The ethyl acetate extracts were dried and evaporated. Chromatography of the residue on silica gel with ethyl acetate/hexane (3:1) gave 266 mg of 3-[-1-(3-mercaptopropyl)-3-indolyl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione, m.p. 155°-157° C.
Reaction SMILES: [Si:1]([O:8][CH2:9][C@@H:10]([NH:26][C:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:30]=[CH:29][C:28]=1[NH2:37])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])=[CH:14][CH:13]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl.[Cl:39][CH2:40][C:41](=N)OCC.C([O-])(O)=O.[Na+]>ClCCCl>[Si:1]([O:8][CH2:9][C@@H:10]([N:26]1[C:27]2[C:36]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[N:30]=[CH:29][C:28]=2[N:37]=[C:41]1[CH2:40][Cl:39])[CH2:11][C:12]1[CH:13]=[CH:14][C:15]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])=[CH:16][CH:17]=1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2]
Reactant: CCOC(=N)CCl
Reactant: CC(C)(C)[Si](C)(C)OC[C@H](Cc1ccc(O[Si](C)(C)C(C)(C)C)cc1)Nc1c(N)cnc2ccccc12
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCCl
Product: CC(C)(C)[Si](C)(C)OC[C@H](Cc1ccc(O[Si](C)(C)C(C)(C)C)cc1)n1c(CCl)nc2cnc3ccccc3c21
Temperature: 70 °C
Yield: 81.2 %

Procedure:
N4-[(1S)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-(4-{[tert-butyl(dimethyl)silyl]oxy}benzyl)ethyl]quinoline-3,4-diamine (23.46 g, 43.6 mmol) was dissolved in 400 mL of dry 1,2-dichloroethane and the yellow solution was stirred under N2. Ethyl 2-chloroethanimidoate hydrochloride (13.8 g, 87.2 mmol) was then added and the reaction mixture was heated to 70° C. overnight. The reaction mixture was then cooled and treated with 300 mL of saturated NaHCO3 solution. The layers were separated and the organic portion was washed sequentially with saturated NaHCO3 solution and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. Chromatography (SiO2, 10-60% ethyl acetate/hexanes) gave 1-[(1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-(4-{[tert-butyl(dimethyl)silyl]oxy}benzyl)ethyl]-2-(chloromethyl)-1H-imidazo[4,5-c]quinoline (21.11 g) as a brown foam.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[NH2:18].[CH:19]([O-])([O-])[O:20]C(Cl)(Cl)Cl>C1(C)C=CC=CC=1>[N:18]([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[O:11][C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:1]=1)=[C:19]=[O:20]
Reactant: [O-]C([O-])OC(Cl)(Cl)Cl
Reactant: Nc1ccccc1Oc1ccc2ccccc2c1
Solvent: Cc1ccccc1
Product: O=C=Nc1ccccc1Oc1ccc2ccccc2c1

Procedure:
To a solution of the title compound of Step B (7.6 g, 32.3 mmol) in 150 mL of toluene was added trichloromethyl orthoformate (6.40 g, 32.3 mmol) at room temperature. The resultant mixture was then heated at reflux overnight. The reaction mixture was then concentrated under reduced pressure to yield the title compound of Step C as an oil which was then used entirely in Step D.
Reaction SMILES: [N+:1]([C:4]1[CH:18]=[CH:17][CH:16]=[CH:15][C:5]=1[CH2:6][NH:7][C@H:8]([C:12]([OH:14])=[O:13])[CH2:9][S:10][CH3:11])([O-])=O.[H][H].C(=O)([O-])[O-].[Na+].[Na+]>[Ni]>[NH2:1][C:4]1[CH:18]=[CH:17][CH:16]=[CH:15][C:5]=1[CH2:6][NH:7][C@H:8]([C:12]([OH:14])=[O:13])[CH2:9][S:10][CH3:11]
Reactant: [H][H]
Reactant: CSC[C@H](NCc1ccccc1[N+](=O)[O-])C(=O)O
Agent: [Ni]
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: CSC[C@H](NCc1ccccc1N)C(=O)O

Procedure:
N-(2-amino-benzyl)-S-methyl-cysteine of the formula ##STR11## was prepared in analogy to Example 1 (b) by reducing N-(2-nitro-benzyl)-S-methyl-cysteine with hydrogen under pressure in the presence of sodium carbonate and Raney nickel. Melting point: 193° C.
Reaction SMILES: [Cl:1][C:2]1[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([NH:16][CH3:17])=[C:7]2[N:14]=[O:15].C[O:19][C:20]1C=CC(C=O)=C[CH:21]=1.CN.[Cl:30][C:31]1[C:40]([O:41][CH3:42])=[CH:39][CH:38]=[C:37]2[C:32]=1[CH:33]=[CH:34][C:35](O)=[C:36]2N=O.ClC1C(OC)=CC=C2C=1C=CC(O)=C2>C(O)C>[Cl:1][C:2]1[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([NH:16][CH3:17])=[C:7]2[N:14]=[O:15].[Cl:30][C:31]1[C:40]([O:41][CH3:42])=[CH:39][CH:38]=[C:37]2[C:32]=1[CH:33]=[CH:34][C:35]([C:20](=[O:19])[CH3:21])=[CH:36]2
Reactant: COc1ccc2c(N=O)c(O)ccc2c1Cl
Reactant: COc1ccc(C=O)cc1
Agent: CN
Agent: CNc1ccc2c(Cl)c(OC)ccc2c1N=O
Agent: COc1ccc2cc(O)ccc2c1Cl
Solvent: CCO
Product: COc1ccc2cc(C(C)=O)ccc2c1Cl

Procedure:
The compound of the title is prepared by following essentially the same procedure described in example 2 but starting from 5-chloro-6-methoxy-2-methylamino-1-nitrosonaphthalene instead of 2-methylamino-1-nitrosonaphthalene and employing 4-methoxybenzaldehyde instead of 4-ethoxybenzaldehyde. Yield 48%. M.p. 247°-48° C. (from ethanol). The starting 5-chloro-6-methoxy-2-methylamino-1-nitrosonaphthalene is prepared through reaction of methylamine with 5-chloro-6-methoxy-1-nitroso-2-naphthol following the procedure described in the second portion of the foregoing example. In its turn this last compound is prepared by nitrosation of 5-chloro-6-methoxy-2-naphthol obtained from (5-chloro-6-methoxy-2-naphthalenyl)-ethanone which is a commercial product.