Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[C:3]2[C:4]([S:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)=[C:5]3[CH:14]([CH2:15][C:16]([OH:18])=[O:17])[CH2:13][CH2:12][N:6]3[C:7]=2[CH:8]=[C:9]([F:11])[CH:10]=1.C[Mg+].[Br-].[Li]C(CC)C.[CH:35](=[O:37])[CH3:36]>C1COCC1>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([S:19][C:4]2[C:3]3[C:2]([CH:35]([OH:37])[CH3:36])=[CH:10][C:9]([F:11])=[CH:8][C:7]=3[N:6]3[CH2:12][CH2:13][CH:14]([CH2:15][C:16]([OH:18])=[O:17])[C:5]=23)=[CH:21][CH:22]=1
Reactant: CC=O
Reactant: O=C(O)CC1CCn2c1c(Sc1ccc(Cl)cc1)c1c(Br)cc(F)cc12
Agent: C[Mg+]
Agent: [Br-]
Agent: [Li]C(C)CC
Solvent: C1CCOC1
Product: CC(O)c1cc(F)cc2c1c(Sc1ccc(Cl)cc1)c1n2CCC1CC(=O)O
Temperature: -78 °C
Reaction time: 0.08 h

Procedure:
To a solution of (+/−)-[8-bromo-9-[(4-chlorophenyl)sulfanyl]-6-fluoro-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl]acetic acid (Example 7, 100 mg, 0.22 mmol) in THF (4 mL) at −78° C. was added 3M MeMgBr (0.26 mmol) followed by the addition of 1.3M sec-BuLi (0.31 mmol). The reaction mixture was stirred at −78° C. for 5 minutes and an excess of acetaldehyde was added. The reaction was stirred at −78° C. for 30 minutes and quenched with saturated aqueous NH4Cl. The phases were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography eluted with EtOAc/Hexanes/AcOH (20:30:1) to provide 65 mg of the title compound as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13](=[O:14])[CH2:12][C:11]([CH3:15])=[N:10]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[F:23][C:24]1[CH:29]=[CH:28][C:27]([N:30]=[C:31]=[O:32])=[CH:26][CH:25]=1>C1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:13](=[O:14])[CH:12]([C:31](=[O:32])[NH:30][C:27]3[CH:28]=[CH:29][C:24]([F:23])=[CH:25][CH:26]=3)[C:11]([CH3:15])=[N:10]2)=[CH:7][CH:8]=1
Reactant: O=C=Nc1ccc(F)cc1
Reactant: COc1ccc(N2N=C(C)CC2=O)cc1
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: COc1ccc(N2N=C(C)C(C(=O)Nc3ccc(F)cc3)C2=O)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
The solution of 4.1 g of 1-(p-methoxyphenyl)-3-methyl-2-pyrazolin-5-one in 75 ml of benzene and 2.5 g of triethylamine is combined with 2.75 g of p-fluorophenylisocyanate while stirring at ambient temperature. After standing overnight, the mixture is evaporated, the residue taken up in 0.3 N hydrochloric acid, the resulting crystals collected, washed with water, dried, triturated with ethyl acetate and recrystallized from methanol to yield the 1-(p-methoxyphenyl)-3-methyl-4-(p-fluorophenylcarbamoyl)-2-pyrazolin-5-one of Formula II with R=OCH3, R'=H and R"=F, melting at 254°-256° (dec.).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.F[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[N+:16]([O-:18])=[O:17].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N+:16]([O-:18])=[O:17])=[CH:4][CH:3]=1
Reactant: O=[N+]([O-])c1ccccc1F
Reactant: Oc1ccc(Cl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1ccccc1Oc1ccc(Cl)cc1
Yield: 66.9 %

Procedure:
A mixture of 4-chlorophenol (2.00 g, 15.56 mmol), 1-fluoro-2-nitrobenzene (2.20 g, 15.56 mmol) and potassium carbonate (2.15 g, 15.56 mmol) in DMF (10 mL) was stirred under reflux for 1 h. After removal of DMF, the residue was dissolved in DCM and washed with NaOH (5%, 3×20 mL) and brine. The organic layer was dried (MgSO4), filtered and evaporated to give 1-(4-chlorophenoxy)-2-nitrobenzene (2.6 g, 67%) as a yellow oil which solidified upon standing at room temperature (mp 33-35° C. from EtOH) and was used in the next step without further purification. Rf: 0.77 (DCM) 1H NMR (270 MHz, CDCl3) δ 696 (2H, AA′BB′), 699 (1H, m), 7.22 (1H, m), 7.31 (2H, AA′BB′), 7.52 (1H, m) and 7.96 (2H, dd, J=8.2, 1.7 Hz)
Reaction SMILES: [N:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][C:4]=1[OH:13])=O.[CH3:14][N:15]1[C:23]2[C:18](=[CH:19][C:20]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:21][CH:22]=2)[C:17]([CH3:30])([CH3:29])[C:16]1=[CH2:31]>C(O)C>[CH3:14][N:15]1[C:16]2([O:13][C:4]3[CH:5]=[CH:6][C:7]4[C:12]([C:3]=3[N:1]=[CH:31]2)=[CH:11][CH:10]=[CH:9][CH:8]=4)[C:17]([CH3:30])([CH3:29])[C:18]2[C:23]1=[CH:22][CH:21]=[C:20]([O:24][C:25]([F:26])([F:27])[F:28])[CH:19]=2
Reactant: C=C1N(C)c2ccc(OC(F)(F)F)cc2C1(C)C
Reactant: O=Nc1c(O)ccc2ccccc12
Solvent: CCO
Product: CN1c2ccc(OC(F)(F)F)cc2C(C)(C)C12C=Nc1c(ccc3ccccc13)O2

Procedure:
A solution of 1-nitroso-2-naphthol (0.50 g, 2.89 mmol) and 1,3,3-trimethyl-5-trifluoromethoxy-2-methylene-indoline (0.71 g, 2.77 mmol) in ethanol (30 ml) was heated under nitrogen and refluxed for 20 hrs. The solvent was then evaporated and the residue was chromatographed over silica (ethyl acetate/petroleum ether 1:10). After crystallization in ethanol, the yield of the pure product (colorless crystals) was 0.2 g (18%).
Reaction SMILES: [OH:1][C@H:2]1[CH2:22][C@@:21]2([CH3:23])[C@@H:13]([CH2:14][CH2:15][C@:16]2([O:24][C:25](=[O:30])[CH2:26][CH2:27][O:28][CH3:29])[C:17](=[O:20])[CH2:18][OH:19])[C@H:12]2[C@H:3]1[C@:4]1([CH3:33])[C:9]([C@@H:10]([CH3:31])[CH2:11]2)=[CH:8][C:7](=[O:32])[CH:6]=[CH:5]1.[C:34](OC(=O)C)(=[O:36])[CH3:35]>>[C:34]([O:19][CH2:18][C:17](=[O:20])[C@:16]1([O:24][C:25](=[O:30])[CH2:26][CH2:27][O:28][CH3:29])[C@:21]2([CH3:23])[C@H:13]([C@H:12]3[C@H:3]([C@@H:2]([OH:1])[CH2:22]2)[C@:4]2([CH3:33])[C:9](=[CH:8][C:7](=[O:32])[CH:6]=[CH:5]2)[C@@H:10]([CH3:31])[CH2:11]3)[CH2:14][CH2:15]1)(=[O:36])[CH3:35]
Reactant: COCCC(=O)O[C@]1(C(=O)CO)CC[C@H]2[C@@H]3C[C@H](C)C4=CC(=O)C=C[C@]4(C)[C@H]3[C@@H](O)C[C@@]21C
Reactant: CC(=O)OC(C)=O
Product: COCCC(=O)O[C@]1(C(=O)COC(C)=O)CC[C@H]2[C@@H]3C[C@H](C)C4=CC(=O)C=C[C@]4(C)[C@H]3[C@@H](O)C[C@@]21C

Procedure:
2.0 g of 11β,21-dihydroxy-17-(3-methoxypropionyloxy)-6α-methyl-1,4-pregnadiene-3,20-dione is reacted analogously to Example 5(c) with acetic anhydride, worked up, and purified, thus isolating 1.36 g of 21-acetoxy-11β-hydroxy-17-(3-methoxypropionyloxy)-6α-methyl-1,4-pregnadiene-3,20-dione, mp 162° C.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:15](Br)[C:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:17].O>CC(C)=O>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:15][C:16](=[O:17])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:4][CH:3]=1
Reactant: Cc1ccc(O)cc1
Reactant: O=C(CBr)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: Cc1ccc(OCC(=O)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
4-Methylphenol (5.4g; 0.05 m) and potassium carbonate (6.9g; excess) were mixed in dry acetone (40 ml.) phenacyl bromide (9.95 g.; 0.05 m) was added and the mixture was boiled under reflux with vigorous stirring for 4 hours. The mixture was cooled to room temperature, poured into iced water extracted with ether, washed with dilute sodium hydroxide solution water, dried and evaporated. The crude product was recrystallised from ethanol to give the title compound, m.p. 65° C.
Reaction SMILES: [H-].[Na+].[O:3]1[C:14]2[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[NH:7][C:6]=2[CH:5]=[C:4]1[C:15]([O:17][CH2:18][CH3:19])=[O:16].[CH3:20]I>CN(C)C=O>[CH3:20][N:7]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=2[C:14]2[O:3][C:4]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:5][C:6]1=2
Reactant: CI
Reactant: CCOC(=O)c1cc2[nH]c3ccccc3c2o1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1cc2c(o1)c1ccccc1n2C
Yield: 84.8 %

Procedure:
To a suspension of sodium hydride (2.5 g) in dimethylformamide (100 ml), a solution of ethyl furo[3,2-b]indole-2-carboxylate (20 g) in dimethylformamide (100 ml) was added dropwise with stirring, then the mixture was stirred for 0.5 hour at room temperature. Methyl iodide (30 g) was added, and the resulting mixture was stirred for 5 hours at room temperature to give ethyl 4-methyl-furo[3,2-b]indole-2-carboxylate (18 g), which was hydrolyzed in a solution of sodium hydroxide (20 g) in water (200 ml) with stirring for an hour to give 4-methyl-furo[3,2-b]indole-2-carboxylic acid (15 g). This carboxylic acid was treated with thionyl chloride (50 ml) in benzene (70 ml) with stirring for an hour at 50° C. to give 4-methyl-furo[3,2-b]indole-2-carbonyl chloride (12 g).
Reaction SMILES: Cl[C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:18])[C:7]([C:15]([OH:17])=[O:16])=[C:8]3[S:14][CH2:13][CH2:12][N:9]32)=[CH:4][C:3]=1[F:19].[C:20]([O:24][C:25]([NH:27][CH:28]1[CH2:32][CH2:31][NH:30][CH2:29]1)=[O:26])([CH3:23])([CH3:22])[CH3:21]>N1C=CC=CC=1>[F:19][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[N:30]1[CH2:31][CH2:32][CH:28]([NH:27][C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:26])[CH2:29]1)[N:9]1[CH2:12][CH2:13][S:14][C:8]1=[C:7]([C:15]([OH:17])=[O:16])[C:6]2=[O:18]
Reactant: CC(C)(C)OC(=O)NC1CCNC1
Reactant: O=C(O)c1c2n(c3cc(Cl)c(F)cc3c1=O)CCS2
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)NC1CCN(c2cc3c(cc2F)c(=O)c(C(=O)O)c2n3CCS2)C1

Procedure:
A mixture of 9.0 g (30 mmol) of 8-chloro-7-fluoro-5-oxo-1,2-dihydro-5H-thiazolo[3,2-a]quinoline-4-carboxylic acid, 8.37 g (45 mmol) of 3-(t-butoxycarbonylamino)pyrrolidine and 100 ml of pyridine is heated at reflux for 18 hours. The solvent is removed in vacuo and the residue triturated with water. The solid which forms is removed by filtration, washed with water and dried in vacuo to give 7-fluoro-8-[3(-t-butoxycarbonylamino)-1-pyrrolidinyl]-5-oxo-1,2-dihydro-5H-thiazolo[3,2-a]quinoline-4-carboxylic acid.
Reaction SMILES: S(Cl)(Cl)=O.[C:5]([C@H:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:18])[N:10]([CH3:19])[C@H:9]1[C:20]1[CH:25]=[C:24]([O:26][CH3:27])[C:23]([O:28][CH3:29])=[C:22]([O:30][CH3:31])[CH:21]=1)(O)=[O:6]>C1C=CC=CC=1>[O:18]=[C:11]1[C:12]2[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8]2[C:5](=[O:6])[C:21]3[C:22]([O:30][CH3:31])=[C:23]([O:28][CH3:29])[C:24]([O:26][CH3:27])=[CH:25][C:20]=3[C:9]=2[N:10]1[CH3:19]
Reactant: COc1cc([C@H]2[C@@H](C(=O)O)c3ccccc3C(=O)N2C)cc(OC)c1OC
Solvent: c1ccccc1
Solvent: O=S(Cl)Cl
Product: COc1cc2c(c(OC)c1OC)C(=O)c1c-2n(C)c(=O)c2ccccc12
Reaction time: 4 h
Yield: 9.1 %

Procedure:
Thionyl chloride (10 mL) was added with stirring to 12j (200 mg, 0.5 mmol). After 4 h, the reaction mixture was diluted with benzene (50 mL) and evaporated to dryness. The dark orange solid was dissolved in chloroform and ether was added to give a dark orange solid (16 mg, 10%): mp 194-195° C.; IR (neat) 2938, 1665, 1463, 1400, 1292, 1125, 1007, 976 cm−1; 1H NMR (CDCl3, 300 MHz) δ8.67 (d, 1H, J=7.8 Hz), 8.32 (d, 1H, J=8. 0 Hz), 7.68 (t, 1H, J=8.0 Hz), 7.45 (t, 1H, J=7.8 Hz), 7.04 (s, 1H), 4.09 (s, 3H), 4.06 (s, 3H), 3.97 (s, 3H), 3.89 (s, 3H); CIMS m/z (relative intensity) 352 (MH+, 100). Anal. Calcd for C20H17NO5: C, H, N.
Reaction SMILES: [Br:1][C:2]1[N:3]=[C:4]([CH:14]2[CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16][CH2:15]2)[N:5]([CH2:7][CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:6]=1.[Cl:27]CCl.[ClH:30].O1CCOCC1>CO>[ClH:27].[ClH:30].[ClH:27].[Br:1][C:2]1[N:3]=[C:4]([CH:14]2[CH2:15][CH2:16][NH:17][CH2:18][CH2:19]2)[N:5]([CH2:7][CH2:8][N:9]2[CH2:10][CH2:11][CH2:12][CH2:13]2)[CH:6]=1
Reactant: CC(C)(C)OC(=O)N1CCC(c2nc(Br)cn2CCN2CCCC2)CC1
Reactant: ClCCl
Agent: Cl
Solvent: C1COCCO1
Solvent: CO
Product: Brc1cn(CCN2CCCC2)c(C2CCNCC2)n1
Reaction time: 1.5 h
Yield: 100 %

Procedure:
Combine tert-butyl 4-(4-bromo-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate (0.80 g, 1.87 mmol), dichloromethane (20 mL), methanol (8 mL), and 4M hydrochloric acid in dioxane (9.36 mL, 20.0 eq) under nitrogen and let stir at room temperature. After 1.5 hours, concentrate in vacuo to give the title compound (0.82 g, 100%). MS (ES) m/z=327 [M]+.
Reaction SMILES: [CH3:1][O:2][N:3]([CH3:14])[C:4](=[O:13])[C@@H:5]([C@H:7]1[CH2:11][O:10][C:9](=[O:12])[NH:8]1)[CH3:6].Br[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[H-].[Na+]>C1COCC1>[CH2:16]([N:8]1[C@@H:7]([C@@H:5]([CH3:6])[C:4]([N:3]([O:2][CH3:1])[CH3:14])=[O:13])[CH2:11][O:10][C:9]1=[O:12])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: CON(C)C(=O)[C@H](C)[C@H]1COC(=O)N1
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CON(C)C(=O)[C@H](C)[C@H]1COC(=O)N1Cc1ccccc1
Reaction time: 2 h
Yield: 97.4 %

Procedure:
To a mixture of crude (R)—N-methoxy-N-methyl-2-((S)-2-oxooxazolidin-4-yl)propanamide (1.3 g, 6.43 mmol) and (bromomethyl)benzene (1.30 mL, 11.4 mmol) in THF (25 mL) was added slowly sodium hydride (60% wt.; 0.643 g) at 0° C. [Caution: gas development!]. The ice bath was removed and the mixture was stirred for ˜2 hr. The mixture were diluted carefully with water and ethyl acetate. The reaction was repeated on the same scale and the mixtures were combined. The aqueous layer was separated and extracted with ethyl acetate (1×). The combined organic layers were dried over sodium sulfate, filtered off and concentrated under reduced pressure. The residue was purified by column chromatography [SiO2, 80 g, EtOAc/heptane=5/95 to 75/25] to provide (R)-2-((S)-3-benzyl-2-oxooxazolidin-4-yl)-N-methoxy-N-methylpropanamide (1.83 g) as a slightly yellow oil, which contained also N-methoxy-N-methylisobutyramide. MS m/z 293.7 (M+H)+; Rt-0.64 min.
Reaction SMILES: Cl[C:2]1[NH:6][C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[N:3]=1.[CH3:11][NH:12][CH3:13].O>CN(C=O)C>[CH3:11][N:12]([CH3:13])[C:2]1[NH:6][C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[N:3]=1
Reactant: CNC
Reactant: Clc1nc2ccccc2[nH]1
Solvent: O
Solvent: CN(C)C=O
Product: CN(C)c1nc2ccccc2[nH]1
Temperature: 200 °C
Yield: 88.5 %

Procedure:
[step 1] Commercially available 2-chloro-1H-benzo[d]imidazole (250 mg, 1.64 mmol) was dissolved in DMF (4.7 mL), dimethylamine (50% aqueous solution, 0.50 mL, 4.92 mmol) was added, and the mixture was stirred with heating at 200° C. for 30 min in an Emrys Optimizer microwave synthesizer. Water was added to the mixture, and the precipitated crystals were collected by suction filtration to give N,N-dimethyl-1H-benzo[d]imidazole-2-amine (234 mg, 89%).
Reaction SMILES: C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N1C=CN=C1.[I:25]I.[CH2:27]([O:34][C:35]1[C:36](=[O:44])[O:37][CH:38]([CH2:41][CH2:42]O)[C:39]=1[OH:40])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>CC#N.CCOCC>[CH2:27]([O:34][C:35]1[C:36](=[O:44])[O:37][CH:38]([CH2:41][CH2:42][I:25])[C:39]=1[OH:40])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: II
Reactant: O=C1OC(CCO)C(O)=C1OCc1ccccc1
Agent: c1c[nH]cn1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Solvent: CCOCC
Product: O=C1OC(CCI)C(O)=C1OCc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 93 %

Procedure:
To an oven dried 250 mL round bottom flask flushed with argon was added 5.8 g (22 mmol) of PPh3, 1.5 g (22 mmol) of imidazole and 80 mL of ether/CH3CN (3/1). The mixture was cooled in an ice water bath with magnetic stirring and 5.6 g (22 mmol) of iodine was added in 4 equal portions with vigorous stirring. The resulting slurry was warmed at room temperature for 20 minutes, cooled to 0° C., and 5.0 g (20 mmol) of 3-benzyloxy-4-hydroxy-5-(2-hydroxyethyl)-2(5H)-furanone dissolved in 20 mL of CH3CN/ether (1/1) was added in one portion and the remainder was rinsed in with 5 mL of ether. The mixture was stirred at 0° C. for 10 minutes, then at room temperature for 30 minutes and quenched by pouring into 150 mL of 10% HCl solution and extracting with 500 mL of ether/hexanes (1/1). The aqueous layer was separated and extracted with 100 mL of ether. The combined organic fractions were washed with 50 mL of H2O and extracted with 5×50 mL of saturated NaHCO3 solution. The combined bicarbonate extracts were washed with 50 mL of ether/hexanes (1/1), acidified to pH below 2 with 10% HCl solution and extracted with 3×200 mL of ether. The combined ether extracts were washed with 100 mL of brine, dried (MgSO4) and concentrated to give 6.7 g, (93% yield) of 3-benzyloxy-4-hydroxy-5-(2-iodoethyl)-2(5H)-furanone as a white solid, which was not further purified: mp 100-104° C., 1H NMR (CDCl3) δ 7.40-7.27 (m, 5H), 5.06, (dd, J=11.4 Hz, 2H), 4.69 (dd, J=3.4, 8.0 Hz, 1H), 3.06 (t, J=7.3 Hz, 2H), 2.41-2.29 (m, 1H), 2.02-1.90 (m, 1H); 13C NMR (CDCl3) δ 170.33, 160.61, 136.32, 128.77, 128.69, 128.58, 120.11, 75.76, 73.39, 35.77, -2.03; Anal Calcd for C13H13O4I: C, 43.35; H, 3.64. Found: C, 43.94; H, 3.69.
Reaction SMILES: [Cl:1][C:2]1[C:7](I)=[CH:6][CH:5]=[CH:4][N:3]=1.[CH:9]1(B(O)O)[CH2:11][CH2:10]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C(OCC)(=O)C.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>[Cl:1][C:2]1[C:7]([CH:9]2[CH2:11][CH2:10]2)=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: OB(O)C1CC1
Reactant: Clc1ncccc1I
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: [K+]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: Clc1ncccc1C1CC1
Temperature: 120 °C
Reaction time: 4 h

Procedure:
To a mixture of 2-chloro-3-iodopyridine (2.39 g, 9.98 mmol), cyclopropylboronic acid (860 mg, 10 mmol) and potassium carbonate (4.14 g, 30.0 mmol) in 1,4-dioxane (50 mL) was added tetrakis(triphenylphosphine)palladium(0) (1.16 g, 1.00 mmol). The reaction mixture was stirred at 120° C. for 4 hours, then diluted with ethyl acetate (50 mL) and filtered. The filtrate was concentrated and the residue was purified by silica gel chromatography (Gradient: 10% to 30% ethyl acetate in petroleum ether) to afford the product as a colorless oil. Yield: 1 g, 6 mmol, 60%. 1H NMR (400 MHz, CDCl3) δ 8.20 (dd, J=4.7, 1.8 Hz, 1H), 7.24-7.28 (m, 1H), 7.14 (br dd, J=7.6, 4.8 Hz, 1H), 2.12-2.21 (m, 1H), 1.04-1.11 (m, 2H), 0.67-0.72 (m, 2H).
Reaction SMILES: Cl.[C:2]([NH:6][CH2:7][CH2:8]Cl)([CH3:5])([CH3:4])[CH3:3].C(=O)([O-])[O-].[K+].[K+].[CH3:16][NH:17][CH3:18]>>[C:2]([NH:6][CH2:7][CH2:8][N:17]([CH3:18])[CH3:16])([CH3:5])([CH3:4])[CH3:3]
Reactant: CNC
Reactant: CC(C)(C)NCCCl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CN(C)CCNC(C)(C)C
Temperature: 140 °C
Yield: 56 %

Procedure:
2-(t-Butylamino)ethylchloride hydrochloride (1.2 g, 7.0 mmol) is dissolved in aqueous dimethylamine solution (40% by weight, 22 mL) in a sealed tube. The mixture is heated in a 140° C. oil bath for six hours, allowed to cool to room temperature, and then is saturated with solid potassium carbonate. The mixture is extracted thrice with ethyl acetate. The combined extracts are dried over anhydrous sodium sulfate, decanted, and concentrated under reduced pressure to give N-t-butyl,N′,N′-dimethylethylenediamine as a light brown liquid (0.57 g, 56%). The crude material is carried on to the following step without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][OH:10])[C:4]=1[CH2:11][OH:12].N1C=CN=C1.[C:18]([Si:22](Cl)([CH3:24])[CH3:23])([CH3:21])([CH3:20])[CH3:19].O>O1CCCC1>[Si:22]([O:10][CH2:9][C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[C:4]=1[CH2:11][OH:12])([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:24])[CH3:23]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: COc1cccc(CO)c1CO
Agent: c1c[nH]cn1
Solvent: C1CCOC1
Solvent: O
Product: COc1cccc(CO[Si](C)(C)C(C)(C)C)c1CO
Temperature: 0 °C
Yield: 52.9 %

Procedure:
3-Methoxy-1,2-benzenedimethanol (1.30 g, 7.73 mmol) obtained from Example 21-(1) was dissolved in tetrahydrofuran (15 ml), and imidazole (526.2 mg, 7.73 mmol) and tert-butylchlorodimethylsilane (1.165 g, 7.73 mmol) were added thereto at 0° C. with stirring. The mixture was stirred at room temperature for 2 hours, then water was added thereto, and the product was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, and the solvent was distilled off under reduced pressure. The residue was subjected to chromatography on a silica gel (60 g) column (eluent; ethyl acetate:hexane=1:4) to afford the title compound (1.156 g, 53% yield) as an oil.
Reaction SMILES: [CH:1]1[C:18]2=[C:19]3[C:8]([C:9]4[C:20]5[C:13](=[CH:14][CH:15]=[CH:16][C:17]2=5)[CH:12]=[CH:11][CH:10]=4)=[CH:7][CH:6]=[CH:5][C:4]3=[CH:3][CH:2]=1.C1C(=O)N([Br:28])C(=O)C1.O>CN(C=O)C>[Br:28][C:14]1[CH:15]=[CH:16][C:17]2[C:18]3[CH:1]=[CH:2][CH:3]=[C:4]4[C:19]=3[C:8]([C:9]3[C:20]=2[C:13]=1[CH:12]=[CH:11][CH:10]=3)=[CH:7][CH:6]=[CH:5]4
Reactant: O=C1CCC(=O)N1Br
Reactant: c1cc2cccc3c4cccc5cccc(c(c1)c23)c54
Solvent: O
Solvent: CN(C)C=O
Product: Brc1ccc2c3cccc4cccc(c5cccc1c52)c43
Temperature: 25 °C
Reaction time: 24 h
Yield: 56.5 %

Procedure:
Following the scheme shown in FIG. 18, perylene (252 mg, 1 mmol) was dissolved in DMF (45 ml), and a solution of NBS (178 mg) dissolved in DMF (10 ml) was added gradually. This was agitated at room temperature for 24 hours. H2O (200 ml) was added, and the product was precipitated and suction filtered. The product was recrystallized with hexane to obtain yellow-brown compound (1) (187 mg, mixture).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][NH:8][C:9]([C:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([C:20]4[C:28]5[O:27][CH2:26][O:25][C:24]=5[CH:23]=[CH:22][C:21]=4[O:29][CH2:30][CH:31]4[CH2:33][CH2:32]4)[C:14]=3[NH:13][CH:12]=2)=[O:10])[CH2:3][CH2:2]1.Cl[C:35]([C:37]1([O:40]C(=O)C)[CH2:39][CH2:38]1)=[O:36]>>[OH:40][C:37]1([C:35]([N:1]2[CH2:2][CH2:3][CH:4]([CH2:7][NH:8][C:9]([C:11]3[C:15]4[N:16]=[CH:17][N:18]=[C:19]([C:20]5[C:28]6[O:27][CH2:26][O:25][C:24]=6[CH:23]=[CH:22][C:21]=5[O:29][CH2:30][CH:31]5[CH2:32][CH2:33]5)[C:14]=4[NH:13][CH:12]=3)=[O:10])[CH2:5][CH2:6]2)=[O:36])[CH2:39][CH2:38]1
Reactant: CC(=O)OC1(C(=O)Cl)CC1
Reactant: O=C(NCC1CCNCC1)c1c[nH]c2c(-c3c(OCC4CC4)ccc4c3OCO4)ncnc12
Product: O=C(NCC1CCN(C(=O)C2(O)CC2)CC1)c1c[nH]c2c(-c3c(OCC4CC4)ccc4c3OCO4)ncnc12

Procedure:
Starting from 4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid (piperidin-4-ylmethyl)-amide (example A144) and acetic acid 1-chlorocarbonyl-cyclopropyl ester the title compound is obtained as colorless solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH2:20][CH2:21][CH2:22]Cl)[CH:14]=3)=[CH:11][C:10]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[NH:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH2:20][CH2:21][CH2:22][N:29]4[CH2:33][CH2:32][CH2:31][CH2:30]4)[CH:14]=3)=[CH:11][C:10]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[N:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1cc(-c2cccc(OCCCCl)c2)n(-c2cccc(Cl)c2)n1
Reactant: C1CCNC1
Solvent: CCO
Product: CCOC(=O)c1cc(-c2cccc(OCCCN3CCCC3)c2)n(-c2cccc(Cl)c2)n1
Yield: 40.3 %

Procedure:
41.5 mg (0.10 mmol) of the compound of Example 68A and 83 μl (0.99 mmol) of pyrrolidine in 3 ml of ethanol are stirred at 80° C. overnight. The reaction mixture is subsequently purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient). 18.3 mg of the title compound are obtained.