Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[NH:3][C:4]2[CH:10]=[C:9]([Cl:11])[C:8]([Cl:12])=[CH:7][C:5]=2[N:6]=1.[H-].[Na+].[CH2:15]([O:22][C@H:23]1[C@H:27]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C@@H:26]([CH2:36][O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[O:25][CH:24]1Cl)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CC#N>[Cl:1][C:2]1[N:3]([C@@H:24]2[O:25][C@H:26]([CH2:36][O:37][CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[C@@H:27]([O:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C@@H:23]2[O:22][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:4]2[CH:10]=[C:9]([Cl:11])[C:8]([Cl:12])=[CH:7][C:5]=2[N:6]=1
Reactant: Clc1nc2cc(Cl)c(Cl)cc2[nH]1
Reactant: ClC1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CC#N
Product: Clc1cc2nc(Cl)n([C@@H]3O[C@H](COCc4ccccc4)[C@@H](OCc4ccccc4)[C@@H]3OCc3ccccc3)c2cc1Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 95 %

Procedure:
Compound 5 (598 mg 2.7 mmole) was dissolved in dry CH3CN(60 ml) and 97% NaH (80 mg, 3 mmole) was added. The mixture was stirred under N2 for 1 hour at room temperature. Then 2,3,5-tri-O-benzyl-D-arabinofuranosyl chloride (prepared from 2,3,5-tri-O-benzyl-1-D-p-nitrobenzoyl-D-arabinofuranose) (1.83 g, 3 mmole)) dissolved in dry CH3CN (20 ml) was added dropwise. The mixture was stirred under N2 for overnight at room temperature. The reaction solution was filtered through Celite. The filtrate was evaporated to give a syrup and this syrup was subjected to flash column chromatography on silica gel (Kieselgel 60, 230-400 mesh) and eluted with CH2Cl2. The fractions containing 133 were combined and evaporated to give 1.6 g (95.0%) of 133. (IR KBr cm-1 : 1140-1060 (C--O--C)).
Reaction SMILES: [CH2:1]([O:4][C:5](=[O:17])[C@H:6]([CH2:15][OH:16])[NH:7][C:8]([O:10]C(C)(C)C)=O)[CH:2]=[CH2:3].C1C(=O)N(OC([CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][NH:33][C:34]2[CH:39]=[CH:38][C:37]([N+:40]([O-:42])=[O:41])=[CH:36][C:35]=2[N+:43]([O-:45])=[O:44])=O)C(=O)C1.C(N(CC)CC)C>Cl.O1CCOCC1>[CH2:1]([O:4][C:5](=[O:17])[C@H:6]([CH2:15][OH:16])[NH:7][C:8](=[O:10])[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][NH:33][C:34]1[CH:39]=[CH:38][C:37]([N+:40]([O-:42])=[O:41])=[CH:36][C:35]=1[N+:43]([O-:45])=[O:44])[CH:2]=[CH2:3]
Reactant: O=C(CCCCCNc1ccc([N+](=O)[O-])cc1[N+](=O)[O-])ON1C(=O)CCC1=O
Reactant: C=CCOC(=O)[C@H](CO)NC(=O)OC(C)(C)C
Agent: Cl
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: C=CCOC(=O)[C@H](CO)NC(=O)CCCCCNc1ccc([N+](=O)[O-])cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 71.6 %

Procedure:
A solution of N-(tert-butoxycarbonyl)-L-serine allyl ester (0.175 g, 0.731 mmol) in 4 M hydrogen chloride/dioxane (2 mL) was stirred at ambient temperature for 40 minutes. The reaction mixture was concentrated on a rotary evaporator and the crude HCl salt was taken up in anhydrous tetrahydrofuran (3 mL). To this solution was added N-succinimidyl 6-(2,4-dinitroanilino)hexanoate (0.288 g, 0.791 mmol) and triethylamine (102 mL, 0.731 mmol). The reaction mixture was stirred at room temperature for 30 minutes and the solvent was evaporated. The residue was partitioned between ethyl acetate and water and the phases were separated. The organic phase was washed with saturated NaHCO3 and saturated NaCl. It was dried over MgSO4, filtered, and concentrated under reduced pressure to yield the crude product (0.293 g) as a yellow oil. Purification using a Thomson Instruments Single Step 12 g silica gel cartridge eluting with 50% hexanes/50% ethyl acetate followed by ethyl acetate gave the product (0.222 g, 72%) as a yellow oil. 1H NMR (DMSO-d6) δ 1.32 (2H, m), 1.52-1.64 (4H, m), 2.15 (2H, t, J=7.0 Hz), 3.44 (2H, m), 3.59 (1H, m), 3.66 (1H, m), 4.33 (1H, m), 4.55 (2H, m), 5.02 (1H, t, J=5.5 Hz), 5.17 (1H, m), 5.28 (1H, m), 5.83 (1H, m), 7.21 (1H, d, J=9.5 Hz), 8.12 (1H, d, J=7.9 Hz), 8.23 (1H, dd, J=2.5 Hz, J=9.4 Hz), 8.85 (2H, m).
Reaction SMILES: [Si]([C:5]1[N:6]=NN[CH:9]=1)(C)(C)C.[N:10]1([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[CH2:17][CH2:16][CH2:15][C@H:11]1[C:12](Cl)=[O:13]>S1(CCCC1)(=O)=O.[Cl-].[Na+].O>[CH2:21]([O:20][C:18]([N:10]1[CH2:17][CH2:16][CH2:15][CH:11]1[C:12]1[O:13][CH:9]=[CH:5][N:6]=1)=[O:19])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: O=C(Cl)[C@@H]1CCCN1C(=O)OCc1ccccc1
Reactant: C[Si](C)(C)c1c[nH]nn1
Agent: [Cl-]
Agent: [Na+]
Solvent: O=S1(=O)CCCC1
Solvent: O
Product: O=C(OCc1ccccc1)N1CCCC1c1ncco1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of TMS-triazole (14.17 g, 100.3 mmol, 1 equiv.) in sulfolane (290 mL) at rt under nitrogen, is added dropwise Z-L-Pro-Cl (26.85 g, 100.3 mmol, 1 equiv.) in sulfolane (70 mL). The resulting mixture is stirred at rt for 30 minutes, then the temperature is elevated to 140° C. for 3 hours. After the reaction mixture is cooled to rt, poured into excess brine and extracted with diethyl ether. The diethyl ether extracts are washed with brine, dried over anhydrous Na2SO4, filtered and evaporated. The residue is purified by flash chromatography (DCM:acetone=9:1) to give the title compound as a light yellow oil.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]2[C:13](=[O:14])[N:12]3[C:15](=[O:22])[C:16]([CH3:21])([CH:18]([CH3:20])[CH3:19])[N:17]=[C:11]3[C:7]2=[N:8][C:9]=1[CH3:10])(=[O:3])[CH3:2].[H-].[Na+].[CH2:25]([OH:31])[C:26]1[O:30][CH:29]=[CH:28][CH:27]=1.C(O)(=O)C>O1CCCC1>[C:1]([C:4]1[C:9]([CH3:10])=[N:8][C:7]([C:11]2[NH:12][C:15](=[O:22])[C:16]([CH:18]([CH3:19])[CH3:20])([CH3:21])[N:17]=2)=[C:6]([CH:5]=1)[C:13]([O:31][CH2:25][C:26]1[O:30][CH:29]=[CH:28][CH:27]=1)=[O:14])(=[O:3])[CH3:2]
Reactant: OCc1ccco1
Reactant: CC(=O)c1cc2c(nc1C)C1=NC(C)(C(C)C)C(=O)N1C2=O
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CC(=O)c1cc(C(=O)OCc2ccco2)c(C2=NC(C)(C(C)C)C(=O)N2)nc1C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 1.0 g of 7-acetyl-2,8-dimethyl-2-isopropyl-5H-imidazo[1',2':1,2]pyrrolo[3,4-b]-pyridine-3(2H),5-dione in 50 mL tetrahydrofuran is added dropwise to a preformed mixture of 0.03 g sodium hydride and 0.35 mL furfuryl alcohol in 50 mL tetrahydrofuran. The reaction mixture is stirred at room temperature overnight, acidified with acetic acid, and concentrated in vacuo. The residue is chromatographed on silica gel using 5% ethyl acetate in methylene chloride as eluant to afford the desired product. Recrystallization from methylene chloride-hexanes gives a solid, mp 133°-136°.
Reaction SMILES: [Br:1][C:2]([Cl:13])([C:9]([F:12])([F:11])[F:10])[CH:3](O)[CH:4]=[C:5]([CH3:7])[CH3:6].[C:14](OC)([O:18][CH3:19])([O:16]C)[CH3:15].O.[O-2].[O-2].[O-2].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.[Al+3].[Al+3]>>[Br:1][C:2]([Cl:13])([C:9]([F:10])([F:11])[F:12])[CH:3]=[CH:4][C:5]([CH3:7])([CH3:6])[CH2:15][C:14]([O:18][CH3:19])=[O:16]
Reactant: COC(C)(OC)OC
Reactant: CC(C)=CC(O)C(Cl)(Br)C(F)(F)F
Agent: O=[Si]=O
Agent: [Al+3]
Agent: [O-2]
Solvent: O
Product: COC(=O)CC(C)(C)C=CC(Cl)(Br)C(F)(F)F
Temperature: 111 °C
Reaction time: 1 h

Procedure:
5-Bromo-5-chloro-4-hydroxy-2-methyl-6,6,6-trifluorohex-2-ene (10.0 g), trimethyl orthoacetate (16.0 g) and Montmorillonite KSF (0.5 g) were charged to a round-bottomed flask fitted with: nitrogen inlet/bubbler, thermometer and still-head. The mixture was heated with agitation, and the methanol-trimethyl orthoacetate distillates were collected until the reactor temperature increased to 111° C. (ca. 1 hr). The reaction was then heated to 135° C. and held for a further 1 hour. The methanol/trimethyl orthoacetate distillates were recharged and the distillation procedure repeated twice. Once the reaction was complete, the Montmorillonite was removed by filtration. The residual trimethyl orthoacetate was then removed by distillation under vacuum (ca. 50° C. ≃100 mmHg) to give the product, methyl 6-bromo-6-chloro-3,3-dimethyl-7,7,7-trifluorohept-4-enoate as a brown oil (7.8 g, 59 g yield).
Reaction SMILES: [C:1]([O:12][C:13]1[CH:43]=[CH:42][C:16]([C:17]([O:19]C2C=CC(C(OC(CCCCCCCC)C(F)(F)F)=O)=CC=2)=[O:18])=[CH:15][CH:14]=1)(=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].O[C:45]1C=CC(C(OC(CCCCCCCC)C(F)(F)F)=O)=CC=1.C1(N=C=NC2CCCCC2)CCCCC1.CN(C1C=CC=CN=1)C>O1CCCC1>[C:1]([O:12][C:13]1[CH:14]=[CH:15][C:16]([C:17]([OH:19])=[O:18])=[CH:42][CH:43]=1)(=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:45]
Reactant: CCCCCCCCCC(=O)Oc1ccc(C(=O)Oc2ccc(C(=O)OC(CCCCCCCC)C(F)(F)F)cc2)cc1
Reactant: CCCCCCCCC(OC(=O)c1ccc(O)cc1)C(F)(F)F
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccccn1
Solvent: C1CCOC1
Product: CCCCCCCCCCC(=O)Oc1ccc(C(=O)O)cc1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
To a solution of the 4-undecanoyloxybenzoic acid )0.3 g) obtained in (1) above and the 1,1,1-trifluoro-2-decyl-4-hydroxybenzoate (0.3 g) obtained in Example 12, (2) in tetrahydrofuran (about 30 ml) were added dicyclohexylcarbodiimide (0.25 g) and dimethylaminopyridine (0.01 g). The mixture was stirred at room temperature for about 20 hours. The solution was distilled to remove the solvent and the residue was dissolved in dichloromethane and washed with water. The organic layer was dried over anhydrous magnesium sulfate and was distilled to remove the solvent. The residue was purified by silica-gel column chromatography (developer : hexane/ethyl acetate=20/1) to obtain the titled compound (0.21 g).
Reaction SMILES: [N+:1]([C:4]1[CH:14]=[C:13]([N+:15]([O-])=O)[C:12]([F:18])=[CH:11][C:5]=1[O:6][CH2:7][C:8](O)=[O:9])([O-])=O.[H][H]>C(O)C.[Pt](=O)=O>[F:18][C:12]1[C:13]([NH2:15])=[CH:14][C:4]2[NH:1][C:8](=[O:9])[CH2:7][O:6][C:5]=2[CH:11]=1
Reactant: [H][H]
Reactant: O=C(O)COc1cc(F)c([N+](=O)[O-])cc1[N+](=O)[O-]
Agent: O=[Pt]=O
Solvent: CCO
Product: Nc1cc2c(cc1F)OCC(=O)N2
Yield: 91.4 %

Procedure:
A suspension of 2,4-dinitro-5-fluorophenoxyacetic acid (0.25 g) and platinum dioxide (80 mg) in ethanol (10 ml) was subjected to catalytic reduction at room temperature under an ordinary pressure until 130 ml of hydrogen was absorbed. The reaction mixture was filtered, and the filtrate was concentrated to give 7-fluoro-6-amino-2H-1,4-benzoxazin-3(4H)-one (0.16 g; yield, 91.4%). M.P., more than 300° C.
Reaction SMILES: C[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([N:11]([S:13]([C:16]2[CH:21]=[CH:20][C:19](F)=[CH:18][CH:17]=2)(=[O:15])=[O:14])[CH3:12])[C:3]=1[CH3:23].[OH:24][CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]([C:32]1[O:33][C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[CH:36]=1)=[O:31]>>[O:33]1[C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[CH:36]=[C:32]1[C:30]([NH:29][CH2:28][CH2:27][CH2:26][CH2:25][O:24][C:19]1[CH:18]=[CH:17][C:16]([S:13]([N:11]([CH3:12])[C:4]2[C:3]([CH3:23])=[CH:2][CH:10]=[CH:9][C:5]=2[C:6]([OH:8])=[O:7])(=[O:14])=[O:15])=[CH:21][CH:20]=1)=[O:31]
Reactant: Cc1ccc(C(=O)O)c(N(C)S(=O)(=O)c2ccc(F)cc2)c1C
Reactant: O=C(NCCCCO)c1cc2ccccc2o1
Product: Cc1cccc(C(=O)O)c1N(C)S(=O)(=O)c1ccc(OCCCCNC(=O)c2cc3ccccc3o2)cc1
Yield: 51 %

Procedure:
The product of Example 2 (0.40 g, 1.24 mmol) was coupled to N-(4-hydroxybutyl)-1-benzofuran-2-carboxamide, prepared according to Example 17, (0.29 g, 1.24 mmol) using the procedure of Example 3 to provide 0.34 g (51% yield) of an off white powder. MP>200° C.; 1H NMR (DMSO-d6): δ 1.35-1.62 (m, CH2, CH2), 1.9 (s, CH3), 3.20 (s, CH3), 3.32-3.41 (m, CH2, CH2), 7.0-7.1 (m, 4 Ar H), 7.35 (t, 1 Ar H), 7.45 (t, 1 Ar H), 7.54 (s, 1 Ar H), 7.65 (d, 1 Ar H), 7.77 (d, 1 Ar H), 7.92 (m, 3 Ar H) 8.8 (t, NH), Electrospray Mass Spec: m/z 537.2 (M+H)+.
Reaction SMILES: [N:1]1([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH:4]([NH2:7])[CH2:3][CH2:2]1.[O:14]=[C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17](=[O:24])[N:16]1[CH2:25][CH2:26][S:27](Cl)(=[O:29])=[O:28]>>[N:1]1([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)[CH2:2][CH2:3][CH:4]([NH:7][S:27]([CH2:26][CH2:25][N:16]2[C:15](=[O:14])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]2=[O:24])(=[O:28])=[O:29])[CH2:5][CH2:6]1
Reactant: O=C1c2ccccc2C(=O)N1CCS(=O)(=O)Cl
Reactant: NC1CCN(c2ccncc2)CC1
Product: O=C1c2ccccc2C(=O)N1CCS(=O)(=O)NC1CCN(c2ccncc2)CC1

Procedure:
2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-ethanesulfonic acid (3,4,5,6-tetrahydro-2H[1,4′]bipyridinyl-4-yl)-amide was prepared by an analogous procedure as described for example 1 i) starting from 638 mg (3.6 mmol) 3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-4-ylamine and 985 mg (1 equiv.) 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethanesulfonyl chloride. The product was obtained in crude form as a light yellow foam. Yield: 860 mg MS (ES+): m/e=415.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[CH3:17].Cl[C:19]1[C:24]([N+:25]([O-:27])=[O:26])=[CH:23][CH:22]=[C:21]([O:28][CH3:29])[N:20]=1.C(N(CC)CC)C>C(O)C>[CH3:29][O:28][C:21]1[N:20]=[C:19]([NH:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[C:5]3[CH2:11][CH:12]2[CH2:16][CH2:15][CH2:14][N:13]2[CH3:17])[C:24]([N+:25]([O-:27])=[O:26])=[CH:23][CH:22]=1
Reactant: COc1ccc([N+](=O)[O-])c(Cl)n1
Reactant: CN1CCC[C@@H]1Cc1c[nH]c2ccc(N)cc12
Solvent: CCN(CC)CC
Solvent: CCO
Product: COc1ccc([N+](=O)[O-])c(Nc2ccc3[nH]cc(CC4CCCN4C)c3c2)n1
Yield: 54 %

Procedure:
(R)-5-Amino-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole and 2-chloro-6-methoxy-3-nitropyridine were used. Triethylamine was used as base, absolute ethanol was used as solvent, and the reaction was heated at reflux for 5.5 hours. Column chromatography afforded the title compound (54%) as a red amorphous solid: 1H NMR (CDCl3) δ 8.80 (br s, NH), 8.37 (d, J=9.1 Hz, 1H), 7.85 (s, 1H), 7.34-7.28 (m, 2H), 7.03 (d, J=2.0 Hz, 1H), 6.14 (d, J=9.1 Hz, 1H), 3.85 (s, 3H), 3.19-3.11 (m, 2H), 2.61 (dd, J=13.8 and 9.5 Hz, 1H), 2.54-2.45 (m, 1H), 2.45 (s, 3H), 2.24 (dd, J=17.1 and 9.3 Hz, 1H), 1.91-1.54 (m, 4H); 13C NMR (CDCl3) δ 166.9, 151.3, 138.2, 134.0, 129.6, 127.8, 123.3, 122.0, 118.6, 114.1, 113.3, 111.1, 102.0, 66.5, 57.5, 54.7, 40.8, 31.6, 29.9, 21.9; HRMS calculated for C20H23N5O3 381.1803, found 381.1799.
Reaction SMILES: C([O:3][C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[C:10]([F:23])[C:11]([F:22])=[C:12]([F:21])[C:13]=2[NH:17]C(=O)C)[N:8]([CH:24]2[CH2:26][CH2:25]2)[CH:7]=1)=[O:5])C.C(OC(=O)CC(=O)C1C(F)=C(F)C(F)=C(F)C=1NC(=O)C)C.C(OC(OCC)OCC)C.C(OC(=O)C)(=O)C>>[CH:24]1([N:8]2[C:9]3[C:14](=[C:13]([NH2:17])[C:12]([F:21])=[C:11]([F:22])[C:10]=3[F:23])[C:15](=[O:16])[C:6]([C:4]([OH:5])=[O:3])=[CH:7]2)[CH2:25][CH2:26]1
Reactant: CCOC(=O)c1cn(C2CC2)c2c(F)c(F)c(F)c(NC(C)=O)c2c1=O
Agent: CCOC(=O)CC(=O)c1c(F)c(F)c(F)c(F)c1NC(C)=O
Solvent: CC(=O)OC(C)=O
Solvent: CCOC(OCC)OCC
Product: Nc1c(F)c(F)c(F)c2c1c(=O)c(C(=O)O)cn2C1CC1

Procedure:
This product can be converted to 5-acetylamino-1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid ethyl ester by a three step reaction. The 2-acetylamino-3,4,5,6-tetrafluoro-β-oxobenzene-propanoic acid ethylester is first treated with triethylorthoformate and acetic anhydride. After removal of the solvent the residue is treated with a solution of cyclopropylamine in t-butanol. After the reaction is complete a solution of potassium t-butoxide in t-butanol is added. The resulting product is 5-acetylamino-1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid ethyl ester. The ester is hydrolyzed to form 1-cyclopropyl-5-amino-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid.
Reaction SMILES: N1C2C(=CC=CC=2)C=C1.C([N:17]1[C:29]2[C:28]([OH:30])=[C:27]3[N:31](C(OC(C)(C)C)=O)[C:32]4[CH:33]=[CH:34][C:35]([Cl:38])=[CH:36][C:37]=4[C:26]3=[CH:25][C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[C:21]([Cl:46])[CH:22]=2)(OC(C)(C)C)=O.O[CH2:48][CH2:49][CH2:50][N:51]1[CH2:55][CH2:54][C@H:53]([NH:56]C(=O)OC(C)(C)C)[CH2:52]1>>[Cl:38][C:35]1[CH:36]=[C:37]2[C:32](=[CH:33][CH:34]=1)[NH:31][C:27]1[C:28]([O:30][CH2:48][CH2:49][CH2:50][N:51]3[CH2:55][CH2:54][C@H:53]([NH2:56])[CH2:52]3)=[C:29]3[NH:17][C:18]4[CH:19]=[CH:20][C:21]([Cl:46])=[CH:22][C:23]=4[C:24]3=[CH:25][C:26]2=1
Reactant: CC(C)(C)OC(=O)n1c2ccc(Cl)cc2c2cc3c4cc(Cl)ccc4n(C(=O)OC(C)(C)C)c3c(O)c21
Reactant: CC(C)(C)OC(=O)N[C@H]1CCN(CCCO)C1
Agent: c1ccc2[nH]ccc2c1
Product: N[C@H]1CCN(CCCOc2c3[nH]c4ccc(Cl)cc4c3cc3c2[nH]c2ccc(Cl)cc23)C1

Procedure:
The title compound was prepared in a manner analogous to Example 28 except the starting indole is 5,7-diBOC-2,10-dichloro-6-hydroxyindolo[2,3-b]carbazole and the reagent is (S)-tert-butyl 1-(3-hydroxypropyl)pyrrolidin-3-ylcarbamate. 1H-NMR (400 MHz, CDCl3) δ ppm 9.92 (s, 2 H), 8.34 (s, 1H), 8.08 (s, 2 H), 7.39-7.29 (m, 4 H), 4.42-4.31 (m, 2 H), 3.90-3.79 (m, 1 H), 3.26 (dd, J=9.8, 6.6 Hz, 1H), 3.09-2.99 (m, 2 H), 2.98-2.86 (m, 2 H), 2.50-2.36 (m, 2 H), 2.15-2.05 (m, 2 H), 1.82-1.71 (m, 1 H); MS (ESI) m/z 465.1 (M−H)−; MS (ESI) m/z 467.0 (M+H)+
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([CH3:9])=[CH:7][N:6]=[C:5]([CH3:10])[C:4]=1[CH3:11].[OH:12]O>C(O)(=O)C.[Pd]>[CH3:1][O:2][C:3]1[C:8]([CH3:9])=[CH:7][N+:6]([O-:12])=[C:5]([CH3:10])[C:4]=1[CH3:11]
Reactant: COc1c(C)cnc(C)c1C
Reactant: OO
Agent: [Pd]
Solvent: CC(=O)O
Product: COc1c(C)c[n+]([O-])c(C)c1C
Temperature: 90 °C

Procedure:
100 g 4-methoxy-2,3,5-trimethylpyridine was dissolved in 300 ml glacial acetic acid and 100 ml 50% hydrogenperoxide and stirred at 30° C. for 1 h. The temperature was gradually heated to70° C. and was maintained for 5 hrs and the temperature increased to 90° C. and a small amount of Pd/C added to destroy excess hydrogenperoxide. After testing that the peroxide was destroyed the solvents were evaporated at reduced pressure. Toluene was added and stripped off to make the product free from water. After the product was dry most of the toluene was evaporated in vacuum. The 4-methoxy-2,3,5-trimethylpyridine N-oxide was diluted with acetic acid and used directly in the next step. The yield of N-oxide was 95%.
Reaction SMILES: Cl.[NH:2]1[CH2:7][CH:6]=[C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([N+:17]([O-:19])=[O:18])[CH:15]=3)[NH:10][CH:9]=2)[CH2:4][CH2:3]1.CN(C)C=O.C(=O)([O-])[O-].[Na+].[Na+].Cl[CH2:32][CH:33]1[CH2:35][CH2:34]1>O>[CH:33]1([CH2:32][N:2]2[CH2:3][CH:4]=[C:5]([C:8]3[C:16]4[C:11](=[CH:12][CH:13]=[C:14]([N+:17]([O-:19])=[O:18])[CH:15]=4)[NH:10][CH:9]=3)[CH2:6][CH2:7]2)[CH2:35][CH2:34]1
Reactant: ClCC1CC1
Reactant: O=[N+]([O-])c1ccc2[nH]cc(C3=CCNCC3)c2c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1ccc2[nH]cc(C3=CCN(CC4CC4)CC3)c2c1
Temperature: 70 °C
Reaction time: 23 h

Procedure:
A mixture of 11.88 g of 3-(1,2,3,6-tetrahydro-4-pyridinyl)-5-nitro-1H-indole hydrochloride, 148 ml of dimethylformamide, 12.72 g of sodium carbonate and 4.8 ml of chloromethylcyclopropane was stirred at 70° C. under an inert atmosphere for 23 hours and the mixture was cooled. 450 ml of distilled water were added to the mixture which was then stirred for one hour and was vacuum filtered. The recovered product was rinsed with water and dried to obtain 10.8 g of raw product. The latter was chromatographed over silica gel and was eluted with a 6-3-1 chloroform-acetone-triethylamine mixture to obtain 8.3 g of 3-(1-cyclopropylmethyl-1,2,3,6-tetrahydro-4-pyridinyl)-5-nitro-1H-indole melting at 187°-188° C.
Reaction SMILES: O.[O:2]=[C:3]1[N:8]([Na])[C:7](=[O:10])[CH:6]=[N:5][NH:4]1.[CH2:11](Br)[CH:12]=[CH2:13]>C(O)CO>[O:2]=[C:3]1[N:8]([CH2:13][CH:12]=[CH2:11])[C:7](=[O:10])[CH:6]=[N:5][NH:4]1
Reactant: O=c1cn[nH]c(=O)n1[Na]
Reactant: C=CCBr
Solvent: O
Solvent: OCCO
Product: C=CCn1c(=O)cn[nH]c1=O
Temperature: 80 °C

Procedure:
A mixture of 6.12 g 3,5-dioxo-4-sodio-2,3,4,5-tetrahydro-1,2,4-triazine monohydrate, 5.81 g allyl bromide and 50 ml ethylene glycol was heated to 80° C. for 4 hours.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([S:19]([CH2:21][CH3:22])=[O:20])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:23](OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:24][CH:25]2[CH2:29][CH2:28][CH2:27][CH2:26]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:41][S:42]([C:45]1[CH:50]=[CH:49][C:48](B(O)O)=[CH:47][CH:46]=1)(=[O:44])=[O:43].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C(OCC)(=O)C.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>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([S:19]([CH2:21][CH3:22])=[O:20])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:23]([C:48]2[CH:49]=[CH:50][C:45]([S:42]([CH3:41])(=[O:44])=[O:43])=[CH:46][CH:47]=2)=[CH:24][CH:25]2[CH2:26][CH2:27][CH2:28][CH2:29]2)(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCS(=O)c1cnc2c(c1)cc(C(=CC1CCCC1)OS(=O)(=O)c1ccc(C)cc1)n2S(=O)(=O)c1ccccc1
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: C1COCCO1
Solvent: CCOC(C)=O
Product: CCS(=O)c1cnc2c(c1)cc(C(=CC1CCCC1)c1ccc(S(C)(=O)=O)cc1)n2S(=O)(=O)c1ccccc1
Yield: 71.7 %

Procedure:
To a mixture of toluene-4-sulfonic acid 1-(1-benzenesulfonyl-5-ethanesulfinyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclopentyl-vinyl ester (80 mg, 0.134 mmol), 4-methylsulfonyl phenylboronic acid (80 mg, 0.401 mmol) and dichlorobis(triphenylphosphine)palladium (II) (9.4 mg, 0.013 mmol) in dioxane (1 mL) was added an aqueous sodium carbonate solution (2 M, 0.2 mL, 0.4 mmol). The resulting mixture was subjected to microwave irradiation for 2 h at 100° C. The mixture was diluted with ethyl acetate (10 mL), washed with a saturated aqueous sodium bicarbonate solution (2×3 mL), brine, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by flash column chromatography (silica gel from QingDao, 200-300 mesh, 25% ethyl acetate/hexanes) afforded 1-benzenesulfonyl-2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-vinyl]-5-ethanesulfinyl-1H-pyrrolo[2,3-b]pyridine (56 mg, 72%) as a light yellow solid: LC/MS m/e calcd for C29H30N2O5S3 [M+H]+ 583.76, observed 583.2.
Reaction SMILES: [H-].[Na+].[CH:3]([O:5][CH2:6][CH3:7])=[O:4].[C:8]1(/[C:14](/[CH2:21][C:22](OCC)=[O:23])=[CH:15]\[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>CCOCC>[OH:23][CH:22]=[C:21](/[C:14](/[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[CH:15]/[C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:3]([O:5][CH2:6][CH3:7])=[O:4]
Reactant: CCOC(=O)/C=C(/CC(=O)OCC)c1ccccc1
Reactant: CCOC=O
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Product: CCOC(=O)/C=C(/C(=CO)C(=O)OCC)c1ccccc1
Yield: 97 %

Procedure:
A stirred mixture of NaH (158.4 mg, 6.6 mmol) and ethyl formate (1.07 ml, 13.2 mmol) in Et2O (5 ml) were refluxed under argon for 15 min. Diethyl (2Z)-3-phenylpent-2-ene-1,5-dioate in Et2O (5 ml) was added dropwise to the above solution over 5 min at rt. The reaction was heated to reflux for 12 hours. The heterogeneous yellow mixture was diluted with Et2O (100 ml), washed with sat. NH4Cl (40 ml), half sat. NH4Cl (40 ml), brine (20 ml), dried with Na2SO4, filtered, and concentrated under reduced pressure. The product diethyl (3E)-2-(hydroxymethylene)-3-phenylpent-3-ene-1,5-dioate was obtained in 97% yield and could be used without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:11]=[C:12]=[O:13])([CH3:10])[CH3:9])=[CH:4][CH:3]=1.[CH:14]1[C:23]2[CH:22]=[CH:21][CH:20]=[C:19]([NH2:24])[C:18]=2[CH:17]=[CH:16][N:15]=1.BrC1C=CC(CN=C=O)=CC=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:11][C:12]([NH:24][C:19]2[CH:20]=[CH:21][CH:22]=[C:23]3[C:18]=2[CH:17]=[CH:16][N:15]=[CH:14]3)=[O:13])([CH3:10])[CH3:9])=[CH:6][CH:7]=1
Reactant: Nc1cccc2cnccc12
Reactant: CC(C)(N=C=O)c1ccc(Cl)cc1
Agent: O=C=NCc1ccc(Br)cc1
Product: CC(C)(NC(=O)Nc1cccc2cnccc12)c1ccc(Cl)cc1

Procedure:
The title compound was prepared using the procedure described in Example 60F using 1-chloro-4-(1-isocyanato-1-methylethyl)benzene and 5-isoquinolinamine instead of the product from Example 60E and 1-bromo-4-(isocyanatomethyl)benzene. MS (ESI+) m/z 355 (M+H)+; MS (ESI−) m/z 353 (M−H)−; 1H NMR (DMSO, 300 MHz) δ 1.63 (s, 6H), 7.23 (s, 1H), 7.37 (d, J 8.8, 2H), 7.47 (d, J 8.8, 2H), 7.73 (t, J 9.2, 1H), 7.93 (d, J 8.1, 1H), 8.25 (d, J 6.4, 1H), 8.39 (d, J 8.1, 1H), 8.67 (d, J 6.4, 1H), 8.87 (s, 1H), 9.58 (s, 1H); Anal. Calcd for C19H18ClN3O.HCl+0.25EtOH: C, 60.40; H, 5.33; N, 10.54. Found: C, 60.82; H, 5.23; N, 10.45.